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Acute coronary syndrome (ACS) is one of the leading causes of death in New Zealand and worldwide. Over 15,000 patients are admitted to New Zealand hospitals with an acute coronary syndrome (ACS) every year and the one-year case fatality is 20%.1 LDL lowering using 3-hydroxy-3-methyl-glutaryl-CoA (HMGCoA) inhibitors (statins) following an acute coronary syndrome has been shown to reduce the risk of heart attack, stroke and all-cause mortality.2 Trials of higher-dose statin therapy compared with lower-dose therapy have been demonstrated to further reduce major vascular events in patients with ACS or stable coronary artery disease.3,4 The early period following an ACS is a critical stage of coronary heart disease; with a high risk of recurrent events and death. The early initiation and maintenance of “high-intensity” statin after ACS is recommended for all patients without contraindications, regardless of initial low density lipoprotein-C (LDL-C) values.5–14 This recommendation comes with the proviso that the use of lower-intensity statin therapy should be considered in patients at increased risk of adverse effects with high-intensity statin therapy, such as in the elderly, patients diagnosed with hepatic or renal impairment, or in the case of a potential risk of drug-drug interactions with other essential concomitant therapies. Prior studies report that only two-thirds of patients who present with an ACS are maintained on a statin at one year15 and three years’16 post-discharge. But to date, no studies have reported the use of high-intensity therapy in New Zealand post-ACS.

“High-intensity” has been variously defined by either the type of statin/dose used in the randomised controlled clinical trials or by the pharmacological effects of statin type/dose on mean LDL-C levels. While the American College of Cardiology/American Heart Association (ACC/AHA) definition of high-intensity statin is based on statin/type and dose,11 the European Society of Cardiology (ESC) definition includes any statin type/dose which can reduce mean LDL by 50%.17 However, in the ESC guideline, data is presented showing the statin type/doses which achieve this LDL reduction, which align well with the ACC/AHA definition. Three of the five more intense versus less intense clinical trials used 80mg of atorvastatin in the “high-intensity” arm,18–20 which lowers LDL-C by approximately 50%.14 Two trials used simvastatin 80mg as the more intense statin arm,21,22 a dose which is no longer recommended due to an excess of myositis, and has a Food and Drug Administration (FDA) black box warning not to prescribe this dose of simvastatin. In one trial a small percentage received atorvastatin 40mg20 and this dose has been included within the ESC and AHA/ACC “high-intensity” statin definition.11,17 Moderate low/medium doses are expected to reduce LDL-C by 30–50%.

Since 2015 the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry has captured data on over 95% of New Zealand patients hospitalised for ACS who underwent coronary angiography. By linking ANZACS-QI registry data to national routine datasets, both initial statin dispensing (type and dose), and subsequent maintenance, can be tracked.23

The aim of this study is therefore to describe the contemporary New Zealand use of high-intensity statin therapy after discharge post-ACS, its maintenance in the first year and the determinants of high-dose statin maintenance at one year.

Methods

Cohort

New Zealand residents (aged over 20y) hospitalised with ACS between 1 Jan 2015 to 31 Dec 2017 and who underwent coronary angiography were identified from the ANZACS-QI registry. Only patients who were alive 30 days after discharge were included to ensure the completeness of early dispensing data. Only the first presentation per person in the three-year period was included.

The ANZACS-QI registry is a web-based electronic database that captures a mandatory dataset in ACS patients who underwent a coronary angiogram, which includes patient demographics, admission ACS risk stratification, cardiovascular risk factors, investigations and management, inpatient outcomes and medications prescribed at discharge. Details regarding the ANZACS-QI programme and registry data collection have been previously reported.24 The registry is subject to monthly auditing to ensure capture of >95% of all patients admitted with suspected ACS who are investigated with coronary angiography, and annual audit to check the accuracy of data entry.

Definitions

ACS included myocardial infarction (MI) or unstable angina. MI was defined according to the contemporary universal definition.25 Variables used for this study included age, sex, ethnicity, prior statin use, diabetes, smoking status, history of cardiovascular disease (CVD), coronary intervention (coronary artery bypass grafting (CABG)) or percutaneous coronary intervention (PCI) and a global estimate of in-hospital mortality post-ACS (the Global Registry of ACS (GRACE) score).26 The GRACE score is reported categorically as low (<1%), medium (1 to <3%) or high (>=3%) as recommended by the ESC. History of CVD was defined as a diagnosis, prior to the current event, of MI/angina, stroke/TIA, peripheral vascular disease or prior radiological evidence of vascular disease. PCI/CABG Sociodemographic variables and residency status were derived from the linked national dataset. For patients in whom more than one ethnic group was recorded, ethnicity was prioritised, in accordance with health sector protocols, in the following order: indigenous Māori, Pacific, Indian and New Zealand European/Other (NZEO).27 Socioeconomic deprivation was assessed by the NZDep13 score,28 a census-based small area 10-point index of deprivation based on the person’s domicile. Prior statin use was derived from the national pharmaceutical claims dataset and was defined as having a statin dispensed during the 90-day period prior to index admission. Concomitant medications dispensed at discharge which should be used with caution in combination with statins were also identified. Because most high-dose statin use was with atorvastatin, we have reported the co-dispensing of medications identified as having a potentially major interaction with that agent.29,30 This group comprises cyclosporin, diltiazem, verapamil, digoxin, erythromycin, clarithromycin, gemfibrozil, ketoconazole, itraconazole and ritonavir.

Statin dispensing analysis

Statin type and dose dispensing were obtained early (within three months of hospital discharge) and late after discharge (in the last three months of the year after discharge) using anonymised linkage to the national pharmaceuticals dataset in order to identify and describe the patients who were initiated on high-dose statins, and those who were maintained on maximum-dose statins at one year.

“High-intensity statin” was defined according to the ACC/AHA definition.11 In New Zealand this comprises atorvastatin 40mg or 80mg, or simvastatin 80mg. For this analysis we chose to divide “high intensity” into the clinical trial high-intensity dose of 80mg atorvastatin recommended in the New Zealand guidelines6,7 and “other high-intensity” statin (atorvastatin 40mg, simvastatin 80mg). Rosuvastatin is not publicly funded in New Zealand so use is very low. All other statin type/doses combinations were considered low/medium dose.

Data linkage

Medication dispensing data, hospitalisation and mortality data required for assessment of medication maintenance were obtained by individual linkage to routine national datasets as previously described.24 An encrypted version of the National Health Index Number (NHI), a unique identifier assigned to everyone who uses health and disability support services (>98% of the population),31 was used to anonymously link in-hospital ANZACS-QI patient records to the national datasets. Dispensing of cardiovascular medications was identified from the national Pharmaceutical Collection (PHARMS), which is jointly administered by the New Zealand Ministry of Health (MOH) and the Pharmaceutical Management Agency of New Zealand. PHARMS contains data regarding government-subsidised medications dispensed by community pharmacies nationwide, which encompasses statin medications relevant to these analyses.32 By 2009, 96% of dispensing episodes were reliably identifiable by NHI numbers. (S Ross, MOH, personal communication). ANZACS-QI validation in the national cohort has shown a high level of statin dispensing capture in PHARMS. In the 2015 to 2017 cohort, similar to the current study cohort, 95% of ACS patients were recorded as prescribed a statin in the ANZACS-QI registry and 93% were recorded as dispensed in PHARMS (unpublished data, manuscript in preparation).

Statistical analysis

Descriptive statistics for continuous variables were summarised as mean with standard deviation, median with inter-quartile range (IQR) and range. Categorical data are reported by frequency and percentage. For continuous variables, comparisons between groups were performed by the Student’s T-test. For categorical variables, Pearson’s chi-squared test was used.

Three multivariable log-binomial regression models were constructed to investigate the variables associated with (i) initial dispensing of 80mg atorvastatin, (ii) statin dose reduction by one year in those initially dispensed 80mg of statin post-discharge, and (iii) statin discontinuation by one year in those initially receiving any dose of statin. The relative risks (RRs) with accompanying 95% confidence intervals (CIs) of covariates were estimated. The covariates adjusted for were age, sex, ethnicity, smoker, diabetes, prior CVD, history of congestive heart failure (CHF), statin three months prior to admission, LDL-C level at baseline, coronary revascularisation, common concomitant medications, district health boards (DHB) and initial statin dose (model iii only).

All P-values reported were two tailed and a P-value <0.05 was considered significant. Data were analysed using SAS statistical package, version 9.4 (SAS Institute, Cary, NC).

Ethics

Linkage of the ANZACS-QI and national datasets has been approved by the National Multi Region Ethics Committee (MEC/07/19/EXP).

Results

The demographics, risk factors, clinical presentation and inpatient management for the 19,867 patient cohort are shown in Table 1. Overall, 92% of patients were dispensed a statin within the first three months post-discharge. Thirty-six percent of patients were dispensed 80mg atorvastatin and 43% “other high-intensity” statin dose, predominantly atorvastatin 40mg. Seventy-nine percent of patients were therefore dispensed high-intensity statins. There were a further 13% who received a low/medium dose and 8% received no statin.

Table 1: Characteristics according to statin dispensing.

ACS = Acute coronary syndrome; CABG = coronary artery bypass grafting; CAD = Coronary Artery Disease; CHF = Coronary Heart Failure; COPD = chronic obstructed pulmonary disease; CVD = Cardiovascular disease; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein-cholesterol; LMS = Left main STEMI; NSTEMI = Non ST elevation myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST elevation myocardial Infarction; VD = Vessel disease.

Those dispensed the maximal 80mg atorvastatin rather than another high-intensity dose were more likely to be younger, be men, be non-European, be current smokers and have an MI rather than unstable angina. They also had higher mean LDL-C, better renal function, more obstructive coronary artery disease and were more likely to have had coronary revascularisation by PCI or CABG. Similar variables differentiated those dispensed 80mg atorvastatin compared with a low/medium dose and no statin although the differences were more marked. Eigh percent of patients were discharged on a medication with the potential to interact with atorvastatin and although they were less likely than others to receive the 80mg dose nearly a quarter of these patients (n=384) were on the 80mg dose.

Who gets 80mg atorvastatin early post discharge? (Table 2, Figure 1)

On multivariable analysis, those who received the maximum 80mg dose of atorvastatin, as opposed to lower doses of statin, were more likely to be younger, male, smoke and have no history of CHF, normal renal function and coronary revascularisation. They were more likely to have been already on statin therapy and to have higher LDL-C cholesterol. Co-prescription of medications with known interactions with statin was also associated with lower use of 80mg atorvastatin.

There was wide variation in the use of the guidelines recommended atorvastatin 80mg dose between DHBs, with use ranging from 15% to 65% of patients. Even after adjustment for covariates, the RR for receiving 80mg statin ranged from as low as 0.29 (95% CIs, 0.22–0.39) to 1.05 (95% CIs, 0.96–1.15).

Table 2: Multivariable model for 80mg atorvastatin at discharge vs all other statin type and dose.

CHF = Congestive heart failure; CVD = Cardiovascular disease; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein-cholesterol.

Figure 1: Percentage of patients who receive high-dose statin at discharge in each district health board area. The high-intensity statin is subdivided into 80mg atorvastatin (dark bar) and other high intensity (lighter bar).

Dispensing of statin at one year post-discharge (See Table 3, Figure 2)

By one year after discharge, 625 (3.2%) of the study cohort had died leaving 19,242 in the one-year dispensing cohort. In the final quarter of the year post-discharge, 29.2% were dispensed atorvastatin 80mg, 35.7% “other high dose”, 14.1% a low/medium dose and 21.1% were not dispensed a statin. 70.5% of those discharged with atorvastatin 80mg continued that dose at one year. Only 14.2% of those initially on 80mg atorvastatin had a dose reduction. A similar number of patients initially dispensed atorvastatin 80mg and other high dose received no statin at one year. Only a small proportion of patients (6.2%) had statins started or dose up-titrated post-discharge.

Multivariable model predictors of high-dose statin maintenance and statin discontinuation by one year. (Appendix Table 1,2)

Table 3: Comparison of early vs one-year statin dispensing.

Other high dose = atorvastatin 40mg and simvastatin 80mg; low/medium dose = other doses of statins.

Figure 2: The distribution of statin dose prior to the index Acute Coronary Syndrome admission, early post-discharge and by one year post-discharge.

Low/medium dose = other doses of statins.

Who receives 80mg of atorvastatin by 1 year? (see Appendix Table 1)

On multivariable regression the strongest predictor of being dispensed 80mg of atorvastatin at one year was being discharged on that dose. Other variables independently associated with receiving 80mg of atorvastatin at one year were younger age, male sex, smoking at admission, being previously on a statin, undergoing revascularisation and having an eGFR ≥30ml/min/1.73m2.

Who discontinues statins? (Appendix Table 2)

After adjustment, the variables associated with statin discontinuation in those initially receiving any dose of statin at discharge were younger age, female sex, not having diabetes, prior CVD, no prior statin, initial low/medium dose, not receiving coronary revascularisation, eGFR<30ml/min/1.73m2 and a high baseline LDL-C. The risk of discontinuation did not differ for those started on atorvastatin 80mg compared with “other high-dose” statins.

Discussion

This study captured over 95% of New Zealand patients discharged after ACS in New Zealand who were actively managed with coronary angiography with or without revascularisation. A key pillar of management for these patients is optimal LDL-C management. We found that 79% were discharged with a high-intensity statin, although only 36% received the maximum, guidelines recommended 80mg dose of atorvastatin. By one year only 14% of those initially on 80mg were down-titrated to a lower dose, and the most important predictor of being on the maximum dose was being discharged on that dose. One in five patients were not dispensed a statin in the last three months of the year post-discharge. After adjustment, an initial 80mg atorvastatin dose and “other high dose” were both associated with a similar and lower risk of discontinuation compared with a low/medium-dose statin. In contrast to the low down-titration rates observed, only a small proportion of patients (6%) initially dispensed a dose less than the maximum atorvastatin dose or no statin had it up-titrated or commenced. Although the range across DHBs in use of high-intensity statin was modest at 73% to 87%, there was a much greater variation, from 15% to 65%, in the use of the 80mg atorvastatin dose. This variation persisted after adjustment for covariates suggesting that much of the variation may be due to local clinical preference.

Comparison with prior studies

The New Zealand utilisation of high-intensity statins is higher than in older registry data for ACS patients in 2003 and 2009 from the US, but this gap is not as large in more recent international reports. Those papers do not report the proportion on 80mg atorvastatin separately. Using the similar definitions for high-intensity statins, the older studies reported rates of prescribing or dispensing of high-intensity statin post ACS of approximately between only 23% and 38%.33–35 As in our study up-titration of doses post-discharge was also infrequent, with the discharge dose strongly associated with dose at one year.34 In a large US study of MI patients in 2014, 72% of those <65y and 57% of those over 65y were discharged on high-intensity statin.36 In a single centre in France in 2016, 61% of post-PCI patients were treated with high-intensity statin.37 We were also able to investigate the relationship between initial dose and discontinuation rates, and found no difference in discontinuation between the highest and “other high” doses. The highest rate of discontinuation was in those patients discharged on low/medium doses. This may reflect the characteristics of patients likely to receive a lower dose.

Atorvastatin 80mg vs other high dose—does it matter?

In the CTT meta-analysis,4 compared with less intensive regimens, more intensive regimens produced a highly significant 15% (p<0.0001) further reduction in major vascular events, consisting of significant reductions in coronary death or non-fatal myocardial infarction of 13% (p<0.0001), in coronary revascularisation of 19% (p<0.0001), and in ischaemic stroke of 16% (p=0.005). For each 1mmol/L reduction in LDL-C, total mortality was reduced by 10% over five years. Statins may also have anti-inflammatory and antioxidant effects beyond the effects of LDL-C lowering that may reduce events. There are no outcome studies, which randomised patients to receive atorvastatin 80mg vs 40mg. There are patients in whom it is clinically appropriate to use lower doses, particularly the very elderly (over 80 years), those with limited life expectancy and those on other medications known to interact with statins. Nevertheless the observed DHB variability after adjustment for covariates suggests that the choice of 40mg vs 80mg is strongly influenced by local clinical preference. By doubling the dose of a statin (atorvastatin 40mg to 80mg) it is expected that there will be a further 6% fall in LDL-C,35,38,39 and based on the well-established relationship between LDL-C lowering and outcomes greater use of 80mg dose would be expected to further improve outcomes.4

There may be an additional benefit of 80mg atorvastatin in patients undergoing PCI. In the recent Statins Evaluation in Coronary Procedures and Revascularization (SECUREPCI) Trial randomised, placebo-controlled trial, which assessed the impact of peri-procedural loading with atorvastatin [two loading doses of 80mg, before and 24h after planned PCI] at 30 days in 4,191 patients with ACS.40 All patients received atorvastatin 40mg per day starting 24h after the second loading dose. The authors found no significant treatment benefit in the overall study population but there was a significant 28% relative risk reduction in a composite of all-cause mortality, myocardial infarction, stroke and unplanned coronary revascularisation in patients who underwent PCI. The benefit was even more pronounced in STEMI patients undergoing primary PCI. These benefits will be offset by even a small increase in side effects if used inappropriately in patients at increased risk for side effects.14

Are we choosing the right patients for atorvastatin 80mg?

In our study there was no evidence, after adjustment for covariates including DHB of domicile, that patients were more likely to require a dose reduction after commencing 80mg compared with 40mg atorvastatin. In addition the 80mg dose was less likely to be used in patients co-administered a drug with a risk of drug-drug interaction. However, we have no more specific information about adverse side effects. It is noteworthy that there were significant numbers of patients on high-intensity statins in this cohort in whom guidelines recommend caution. This includes the very elderly where side effects may occur from over medication, those with severe chronic kidney and hepatic disease and patients on essential concomitant medications with a risk of drug-drug interaction. In the current study, 15% of those over 80 years, and nearly a quarter of the 8% of patients on concomitant medications with risk of drug interactions received the atorvastatin 80mg dose. Conversely, there were many patients without obvious reasons for caution who could potentially have been treated with a higher dose of statin.

Clinical implications

In the year post-ACS discharge, patients usually continue on the dose of statin they were discharged with, but nearly one in five patients initially dispensed statin were not dispensed a statin in the last three months of the year post-discharge. Because the maximum dispensing period in New Zealand is three months, this finding suggests sub-optimal maintenance or discontinuation of medication for those patients. It is therefore important that both the optimal dose be chosen for each patient in-hospital, and that patients then be supported to continue with their medication.

Choice of the appropriate statin dose is usually made in-hospital by the medical team, although in some cases, such as prior intolerance or abnormal liver function tests, up-titration as tolerated, from an initial low dose, may be done by the secondary and/or primary care teams after discharge. Supporting longer-term maintenance in ACS patients begins during the hospital admission and is supported by in-hospital and early post-discharge cardiac rehabilitation. In New Zealand it then continues under the supervision of the primary care team. Commencement and continuation of statins and other medications of proven clinical benefit which have been started in hospital requires optimal performance across this care continuum. Important components include:

1. Medical staff having access to evidence-based recommendations for medications and doses. In New Zealand initial medications post-ACS are often prescribed by junior medical staff who rotate through the coronary care unit and are under the supervision of multiple different cardiologists, which can result in variation in practice. Each unit should have a locally endorsed medication guideline which is regularly updated according to evolving evidence, and which is used by all medical team members. It should be based on national and international guidelines and give specific advice regarding recommended medications and doses which takes into account patient-specific factors including age, liver and renal function and concomitant medications. Although for many units this will be a paper-based guideline there is an increasing opportunity to incorporate this content within electronic prescribing systems, which can include a default list of medications and doses for each condition and provide advice/alerts as appropriate.

2. Involvement of the medical, nursing, cardiac rehabilitation team and pharmacists while the patient is in hospital, to both educate and support patients and their families regarding the benefits and potential risk of medications. The non-medical health professionals, if enabled to do so, also provide an important cross-check on medical prescribing decisions. Several New Zealand cardiology units now utilise the patient oriented “My Heart Recovery Plan”. This was developed in 2019 by the Health Quality and Safety Commission and ANZACS-QI, and it is endorsed for use nationally by the National Cardiac Network. It is a checklist designed to be used interactively by patients and their in-hospital medical, nursing and pharmacy team to support their understanding of their medications, the importance of continuing them long-term, whether they have been invited to cardiac rehabilitation, whether a follow-up appointment is arranged with their general practitioner and whether they need psychological support post-discharge. More widespread uptake and systematic implementation of this tool should be considered.

3. Practical considerations include simplifying the dosing regimen and encouraging patients to have their medications blister packed or a similar process which has been shown to improve adherence.41 Financial barriers do have an impact on adherence and these should be addressed.41 The default change per item dispensed in New Zealand is $5. Although there are programmes to reduce this for high-needs populations, our experience is that there are still patients who defer medications because of cost considerations.

4. Facilitation of referral to culturally appropriate cardiac rehabilitation programs after discharge to continue to educate and support patients and facilitate the transition to primary care.42

5. Primary care based self-monitoring and self-management programmes have proven effectiveness to improve medication adherence use, and utilising technology to ensure re-prescription of medication continues after discharge is a promising approach.41

6. Publication of data is an important way to feedback to clinicians and modify prescribing behavior.43 In particular, publication of the wide variation in use of the atorvastatin 80mg dose between DHBs is expected to prompt units to review their local guidelines. ANZACS-QI will continue to report back to the DHBs on high-intensity statin use as part of its annual Post-ACS Statin Adherence report to allow progress to be tracked.

Limitations

We used dispensing of statin as a marker of maintenance but not everyone who is dispensed a drug routinely is necessarily taking the medication. We had no other measures of adherence, nor did we have information about patient preferences. In some cases patients may be wary of high doses of a statin but accept a lower dose. Achieved LDL-C post discharge was not available for this study. The cohort comprised those patients who underwent invasive coronary angiography for whom we would expect intensive secondary prevention including high-intensity statins to be appropriate. The ANZACS-QI registry has very high rates of capture for these patients across New Zealand.44 Approximately 40% of patients with ACS do not receive coronary angiography and are not included in this analysis.45 However, of younger ACS patients between 60 and 70y, 70% receive an angiogram, and of those under 60y this increases to 80%.46 It is likely that use of high-intensity statin would be lower in those not receiving an angiogram given the high burden of comorbidity previously documented in such patients.45,47 No outcome data are presented and apart from medication discontinuation we cannot identify statin-specific side effects.

Conclusion

Only 36% of ACS patients who received invasive investigation post-ACS received guideline-recommended dose of 80mg atorvastatin. The dose of statin at hospital discharge is the most important determinant of dose by one year. The atorvastatin 80mg dose was not associated with higher discontinuation rates. Further optimisation of dosage at discharge by the secondary care team is feasible in New Zealand, for many clinically appropriate patients, and is an opportunity to achieve better long-term LDL-C reduction and thus improved clinical outcomes. GPs and primary care teams should have a greater role in medication up-titration, and systems need to be developed to ensure regular re-prescription of medication.

Appendix

Appendix Table 1: Multivariable regression analysis: variables associated with being dispensed 80mg atorvastatin at one year.

CHF = Congestive heart failure; CVD = Cardiovascular disease; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein-cholesterol.

Appendix Table 2: Multivariable regression analysis: variables associated with statin discontinuation by one year in patients initially dispensed statin.

CHF = Congestive heart failure; CVD = Cardiovascular disease; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein-cholesterol.

Summary

Abstract

Aim

A key pillar in the medical management of patients after an acute coronary syndrome (ACS) is the early initiation and maintenance of “high-intensity” statin therapy to lower low-density lipoprotein cholesterol (LDL-C) and to improve clinical outcomes. The aim of this study was to describe the New Zealand utilisation of high-intensity statin therapy in the first year post-ACS.

Method

19,867 New Zealand patients (≥20 years), discharged post-ACS event (2015–2017) were identified from the All New Zealand ACS Quality Improvement (ANZACS-QI) registry and anonymously linked with the national pharmaceutical dataset to identify statin dispensing early (0–3 months) and late (9–12 months) post-discharge. “High intensity” statin was subdivided into the New Zealand guidelines recommended dose (80mg atorvastatin) and “other high-intensity” statin (atorvastatin 40mg, simvastatin 80mg). All other statin doses were classified as “low/medium dose”.

Results

Seventy-nine percent were initially dispensed high-intensity statins. Thirty-six percent of the overall cohort received 80mg atorvastatin and 43% a lower “other high-intensity” statin. A further 13% received a medium/low dose and 8% no statin. By 12 months, 29% were dispensed atorvastatin 80mg, 36% another high dose, 14% a low/medium dose and 21% no statin. Only 14% of those initially on 80mg atorvastatin had a statin dose reduction. After multivariable adjustment, the risk of discontinuation was the same for those started on atorvastatin 80mg compared with “other high dose”, and lower than for those started on a low/medium dose. Few patients (6.2%) had statins started, or dose up-titrated post-discharge. There is clinically unexplained variation in the use of the highest atorvastatin 80mg dose between district health boards (range 15% to 65%).

Conclusion

Seventy-nine percent were initially dispensed high-intensity statins. Thirty-six percent of the overall cohort received 80mg atorvastatin and 43% a lower “other high-intensity” statin. A further 13% received a medium/low dose and 8% no statin. By 12 months, 29% were dispensed atorvastatin 80mg, 36% another high dose, 14% a low/medium dose and 21% no statin. Only 14% of those initially on 80mg atorvastatin had a statin dose reduction. After multivariable adjustment, the risk of discontinuation was the same for those started on atorvastatin 80mg compared with “other high dose”, and lower than for those started on a low/medium dose. Few patients (6.2%) had statins started, or dose up-titrated post-discharge. There is clinically unexplained variation in the use of the highest atorvastatin 80mg dose between district health boards (range 15% to 65%).

Author Information

Andrew J Kerr, Cardiologist, Counties Manukau District Health Board; Adjunct Associate Professor of Medicine, University of Auckland, Auckland; Sirisha Mitnala, Advanced Trainee in Cardiology, Counties Manukau District Health Board, Auckland; Mildred Lee, Biostatistician, Counties Manukau District Health Board, Auckland; Harvey D White, Cardiologist, Auckland City Hospital, Green Lane Cardiovascular Services, Auckland.

Acknowledgements

ANZACS-QI programme implementation, coordination and analysis: The ANZACS-QI software was developed and supported by Enigma Solutions. Programme implementation is coordinated by the National Institute for Health Innovation (NIHI) at the University of Auckland. The ANZACS-QI programme is funded by the New Zealand Ministry of Health. We thank the the National Health Board Analytic Services and Pharmac for enabling use of the national data sets. We also thank the VIEW team at the School of Population Health, University of Auckland for the curation and linkage of the national data. ANZACS-QI Governance group: Andrew Kerr (chair), Chris Nunn, Dean Boddington, Gary Sutcliffe, Gerry Devlin, Harvey White, John Edmond, Jonathon Tisch, Kim Marshall, Mayanna Lund, Michael Williams (deputy chair), Nick Fisher, Seif El Jack, Sue Riddle, Tony Scott. ANZACS-QI Project management: Kristin Sutherland (Project Manager), Charmaine Flynn (Northern Coordinator), Maxine Rhodes (Southern Coordinator), Anna-Marie Rattray (Research Assistant). Data analysis: Mildred Lee. Data management: Billy Wu (SOPH), Michelle Jenkins (NIHI), John Faatui (NIHI). We acknowledge all the New Zealand cardiologists, physicians, nursing staff and radiographers and all the patients who have supported and contributed to ANZACS-QI. ANZACS-QI hospital coordinators: Ascot Angiography: Summerscales, I. Money, J. Ashburton: Wilson, S. Auckland Hospital Belz, L. Stewart, R. Marshall, K. Bay of Islands: Cochran, G. Christchurch Hospital: Jackson, M. Sutherland, J. McLaren, S. Clutha Hospital: Reed, G. Campbell, B. McElrea, J. Dargaville: Cripps, J. Katipa, K. Dunedin Hospital: Foote, C. Dunstan: Nixon, G. Shaw, M. Klahn, R. Gisborne: Low, T. Gore: Lindley, G. Whitten, C. Grey Base Hospital: Smith, L. Jennings, M. Hawke’s Bay Hospital Soldiers Memorial: Brown, G. Grant, P. Hutt Hospital: Pinfold, S. Ferrier, K. Kitchen, R. Kaikoura Hospital: McCullough, C. Kaitaia Hospital: Thompson, R. Smith, N. Lakes District Hospital: Burt, J. Mercy Angiography: Shah, A. Ubod, B. Mercy Heart Centre: Hall, S. Middlemore: Mcintosh, R. McLachlan, A. Midland Cardiovascular Services: Phillips, K. Nelson Hospital: Besley, J. Abernethy, H. North Shore Hospital: Gray, L. Oamaru: Gonzales, R. Clare, L. Palmerston North Hospital: Kinloch, D. Rawene Hospital: Dorsay, C. Rotorua Hospital: Colby, C. Southland Hospital: Byers, R. Ghosh, P. St Georges Hospital: Lissette, J. Lewis, K. Taranaki Base Hospital: Ternouth, I. Spurway, M. Taumaranui: Pointon, L. Taupo Hospital: McAnanay, J. Tauranga Hospital: Goodson, J. Te Kuiti: Te Wano, T. Thames: Stutchbury, D. Timaru Hospital: Addidle, D. Tokoroa: Huitema, V. Waikato Hospital: Emerson, C. Pilay, R. Wairarapa Hospital: Matthews, T. Wairau Hospital: Langford, S. Ballagh, D. Waitakere Hospital: Long, L. Waitemata Hospital: Newcombe, R. Wakefield Private Hospital: Murphy, S. Wellington Hospital: Scott, B. Wylie, D. Whaktane Hospital: Bentley-Smith, M. Whanganui Hospital: Thompson, T. Whangarei Hospital: Vallancey, S.

Correspondence

Associate Professor Andrew Kerr, Department of Cardiology, Middlemore Hospital, Otahuhu, Auckland 93311.

Correspondence Email

andrew.kerr@middlemore.co.nz

Competing Interests

Dr White reports grants and personal fees from Eli Lilly and Company, personal fees and other from AstraZeneca, grants and personal fees from Omthera Pharmaceuticals, grants and personal fees from Pfizer USA, grants and personal fees from Eisai Inc., grants and personal fees from DalCor Pharma UK Inc., personal fees from Sirtex, personal fees from Acetelion, grants and personal fees from CSL Behring LLC, grants and personal fees from American Regent, grants and personal fees from Sanofi-Aventis Australia Pty Ltd, grants and personal fees from Esperion Therapeutics Inc., personal fees from Genentech Inc., grants and personal fees from Sanofi-Aventis, grants from National Heart, Lung and Blood Institute, outside the submitted work; Dr Kerr reports grants from HRC during the conduct of the study.

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3. Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. Journal of the American College of Cardiology. 2006; 48:438–45.

4. Cholesterol Treatment Trialists C. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. The Lancet. 2010; 376:1670–81.

5. Reiner Ž, Catapano AL, De Backer G, et al. ESC/EAS Guidelines for the management of dyslipidaemias. European heart journal. 2011; 32:1769–818.

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8. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2019; 73:3168–209.

9. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology. 2013; 61:485–510.

10. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology. 2014; 64:e139–e228.

11. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 129:S1–45.

12. Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). European Heart Journal. 2016; 37:267–315.

13. Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). European Heart Journal. 2018; 39:119–77.

14. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. European Heart Journal. 2019; 31.

15. Thornley S, Marshall R, Chan WC, et al. Four out of ten patients are not taking statins regularly during the 12 months after an acute coronary event. European Journal of Preventive Cardiology. 2012; 19:349–57.

16. Grey C, Jackson R, Wells S, et al. Maintenance of statin use over 3 years following acute coronary syndromes: a national data linkage study (ANZACS-QI-2). Heart. 2014; 100:770–4.

17. Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. 2016; 1:2999–3058.

18. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. New England Journal of Medicine. 2004; 1:1495–504.

19. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. New England Journal of Medicine. 2005; 1:1425–35.

20. Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005; 294:2437–45.

21. de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA. 2004; 292:1307–16.

22. Study of the Effectiveness of Additional Reductions in Cholesterol Homocysteine Collaborative Group, Armitage J, Bowman L, et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. 2010; 376:1658–69.

23. Kerr AJ, Looi JL, Garofalo D, Wells S, McLachlan A. Acute Predict: a clinician-led cardiovascular disease quality improvement project (Predict-CVD 12). Heart, Lung & Circulation. 2010; 19:378–83.

24. Kerr A, Williams MJ, White H, et al. The All New Zealand Acute Coronary Syndrome Quality Improvement Programme: Implementation, Methodology and Cohorts (ANZACS-QI 9). New Zealand Medical Journal. 2016; 129:23–36.

25. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD. Third universal definition of myocardial infarction. European Heart Journal. 2012; 33:2551–67.

26. Granger CB, Goldberg RJ, Dabbous O, et al. Predictors of hospital mortality in the global registry of acute coronary events. Archives of Internal Medicine. 2003; 163:2345–53.

27. Ministry of Health. Ethnicity data protocols for the Health and Disability Sector. Wellington, New Zealand, 2004.

28. Atkinson J, Salmond C, Crampton P. NZDep2013 Index of Deprivation. Dunedin: University of Otago, 2014.

29. Kellick KA, Bottorff M, Toth PP. A clinician’s guide to statin drug-drug interactions. J. 2014; 8:S30–46.

30. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006; 80:565–81.

31. Ministry of Health. National Health Index data dictionary (version 5.3). Ministry of Health 2009.

32. Ministry of Health. Pharmaceutical collection, http://www.health.govt.nz/nz-health-statistics/national-collections-and-surveys/collections/pharmaceutical-collection. 2012.

33. Arnold SV, Kosiborod M, Tang F, et al. Patterns of statin initiation, intensification, and maximization among patients hospitalized with an acute myocardial infarction. Circulation. 2014; 129:1303–9.

34. Arnold SV, Spertus JA, Masoudi FA, et al. Beyond Medication Prescription as Performance MeasuresOptimal Secondary Prevention Medication Dosing After Acute Myocardial Infarction. Journal of the American College of Cardiology. 2013; 62:1791–801.

35. Javed U, Deedwania PC, Bhatt DL, et al. Use of intensive lipid-lowering therapy in patients hospitalized with acute coronary syndrome: An analysis of 65,396 hospitalizations from 344 hospitals participating in Get With The Guidelines (GWTG). American Heart Journal. 2011; 161:418–24.e1-3.

36. Rosenson RS, Farkouh ME, Mefford M, et al. Trends in Use of High-Intensity Statin Therapy After Myocardial Infarction, 2011 to 2014. Journal of the American College of Cardiology. 2017; 69:2696–706.

37. Guedeney P, Baber U, Claessen B, et al. Temporal trends, determinants, and impact of high-intensity statin prescriptions after percutaneous coronary intervention: Results from a large single-center prospective registry. American Heart Journal. 2019; 207:10–8.

38. Jones PH, McKenney JM, Karalis DG, Downey J. Comparison of the efficacy and safety of atorvastatin initiated at different starting doses in patients with dyslipidemia. American Heart Journal. 2005; 149:e1.

39. Kaul U, Varma J, Kahali D, et al. Post-marketing study of clinical experience of atorvastatin 80 mg vs 40 mg in Indian patients with acute coronary syndrome- a randomized, multi-centre study (CURE-ACS). J Assoc Physicians India. 2013; 61:97–101.

40. Berwanger O, Santucci EV, de Barros ESPGM, et al. Effect of Loading Dose of Atorvastatin Prior to Planned Percutaneous Coronary Intervention on Major Adverse Cardiovascular Events in Acute Coronary Syndrome: The SECURE-PCI Randomized Clinical Trial. JAMA. 2018; 319:1331–40.

41. Ryan R, Santesso N, Lowe D, et al. Interventions to improve safe and effective medicines use by consumers: an overview of systematic reviews. Cochrane Database Syst Rev. 2014.

42. McLachlan A, Doolan-Noble F, Lee M, McLean K, Kerr AJ. The electronic tracking of referral and attendance at cardiac rehabilitation in Counties Manukau Health: a potential model for New Zealand. New Zealand Medical Journal. 2016; 129:64–71.

43. Hamblin R, Shuker C, Stolarek I, Wilson J, Merry AF. Public reporting of health care performance data: what we know and what we should do. New Zealand Medical Journal. 2016; 129:7–17.

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45. Chan D, Ghazali S, Selak V, Lee M, Scott T, Kerr A. What is the Optimal Rate of Invasive Coronary Angiography After Acute Coronary Syndrome? (ANZACS-QI 22). Heart, Lung & Circulation. 2019; 02:02.

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47. Earle NJ, Poppe KK, Doughty RN, Rolleston A, Kerr AJ, Legget ME. Clinical Characteristics and Burden of Risk Factors Among Patients With Early Onset Acute Coronary Syndromes: The ANZACS-QI New Zealand National Cohort (ANZACS-QI 17). Heart, Lung & Circulation. 2018; 27:568–75.

Contact diana@nzma.org.nz
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Acute coronary syndrome (ACS) is one of the leading causes of death in New Zealand and worldwide. Over 15,000 patients are admitted to New Zealand hospitals with an acute coronary syndrome (ACS) every year and the one-year case fatality is 20%.1 LDL lowering using 3-hydroxy-3-methyl-glutaryl-CoA (HMGCoA) inhibitors (statins) following an acute coronary syndrome has been shown to reduce the risk of heart attack, stroke and all-cause mortality.2 Trials of higher-dose statin therapy compared with lower-dose therapy have been demonstrated to further reduce major vascular events in patients with ACS or stable coronary artery disease.3,4 The early period following an ACS is a critical stage of coronary heart disease; with a high risk of recurrent events and death. The early initiation and maintenance of “high-intensity” statin after ACS is recommended for all patients without contraindications, regardless of initial low density lipoprotein-C (LDL-C) values.5–14 This recommendation comes with the proviso that the use of lower-intensity statin therapy should be considered in patients at increased risk of adverse effects with high-intensity statin therapy, such as in the elderly, patients diagnosed with hepatic or renal impairment, or in the case of a potential risk of drug-drug interactions with other essential concomitant therapies. Prior studies report that only two-thirds of patients who present with an ACS are maintained on a statin at one year15 and three years’16 post-discharge. But to date, no studies have reported the use of high-intensity therapy in New Zealand post-ACS.

“High-intensity” has been variously defined by either the type of statin/dose used in the randomised controlled clinical trials or by the pharmacological effects of statin type/dose on mean LDL-C levels. While the American College of Cardiology/American Heart Association (ACC/AHA) definition of high-intensity statin is based on statin/type and dose,11 the European Society of Cardiology (ESC) definition includes any statin type/dose which can reduce mean LDL by 50%.17 However, in the ESC guideline, data is presented showing the statin type/doses which achieve this LDL reduction, which align well with the ACC/AHA definition. Three of the five more intense versus less intense clinical trials used 80mg of atorvastatin in the “high-intensity” arm,18–20 which lowers LDL-C by approximately 50%.14 Two trials used simvastatin 80mg as the more intense statin arm,21,22 a dose which is no longer recommended due to an excess of myositis, and has a Food and Drug Administration (FDA) black box warning not to prescribe this dose of simvastatin. In one trial a small percentage received atorvastatin 40mg20 and this dose has been included within the ESC and AHA/ACC “high-intensity” statin definition.11,17 Moderate low/medium doses are expected to reduce LDL-C by 30–50%.

Since 2015 the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry has captured data on over 95% of New Zealand patients hospitalised for ACS who underwent coronary angiography. By linking ANZACS-QI registry data to national routine datasets, both initial statin dispensing (type and dose), and subsequent maintenance, can be tracked.23

The aim of this study is therefore to describe the contemporary New Zealand use of high-intensity statin therapy after discharge post-ACS, its maintenance in the first year and the determinants of high-dose statin maintenance at one year.

Methods

Cohort

New Zealand residents (aged over 20y) hospitalised with ACS between 1 Jan 2015 to 31 Dec 2017 and who underwent coronary angiography were identified from the ANZACS-QI registry. Only patients who were alive 30 days after discharge were included to ensure the completeness of early dispensing data. Only the first presentation per person in the three-year period was included.

The ANZACS-QI registry is a web-based electronic database that captures a mandatory dataset in ACS patients who underwent a coronary angiogram, which includes patient demographics, admission ACS risk stratification, cardiovascular risk factors, investigations and management, inpatient outcomes and medications prescribed at discharge. Details regarding the ANZACS-QI programme and registry data collection have been previously reported.24 The registry is subject to monthly auditing to ensure capture of >95% of all patients admitted with suspected ACS who are investigated with coronary angiography, and annual audit to check the accuracy of data entry.

Definitions

ACS included myocardial infarction (MI) or unstable angina. MI was defined according to the contemporary universal definition.25 Variables used for this study included age, sex, ethnicity, prior statin use, diabetes, smoking status, history of cardiovascular disease (CVD), coronary intervention (coronary artery bypass grafting (CABG)) or percutaneous coronary intervention (PCI) and a global estimate of in-hospital mortality post-ACS (the Global Registry of ACS (GRACE) score).26 The GRACE score is reported categorically as low (<1%), medium (1 to <3%) or high (>=3%) as recommended by the ESC. History of CVD was defined as a diagnosis, prior to the current event, of MI/angina, stroke/TIA, peripheral vascular disease or prior radiological evidence of vascular disease. PCI/CABG Sociodemographic variables and residency status were derived from the linked national dataset. For patients in whom more than one ethnic group was recorded, ethnicity was prioritised, in accordance with health sector protocols, in the following order: indigenous Māori, Pacific, Indian and New Zealand European/Other (NZEO).27 Socioeconomic deprivation was assessed by the NZDep13 score,28 a census-based small area 10-point index of deprivation based on the person’s domicile. Prior statin use was derived from the national pharmaceutical claims dataset and was defined as having a statin dispensed during the 90-day period prior to index admission. Concomitant medications dispensed at discharge which should be used with caution in combination with statins were also identified. Because most high-dose statin use was with atorvastatin, we have reported the co-dispensing of medications identified as having a potentially major interaction with that agent.29,30 This group comprises cyclosporin, diltiazem, verapamil, digoxin, erythromycin, clarithromycin, gemfibrozil, ketoconazole, itraconazole and ritonavir.

Statin dispensing analysis

Statin type and dose dispensing were obtained early (within three months of hospital discharge) and late after discharge (in the last three months of the year after discharge) using anonymised linkage to the national pharmaceuticals dataset in order to identify and describe the patients who were initiated on high-dose statins, and those who were maintained on maximum-dose statins at one year.

“High-intensity statin” was defined according to the ACC/AHA definition.11 In New Zealand this comprises atorvastatin 40mg or 80mg, or simvastatin 80mg. For this analysis we chose to divide “high intensity” into the clinical trial high-intensity dose of 80mg atorvastatin recommended in the New Zealand guidelines6,7 and “other high-intensity” statin (atorvastatin 40mg, simvastatin 80mg). Rosuvastatin is not publicly funded in New Zealand so use is very low. All other statin type/doses combinations were considered low/medium dose.

Data linkage

Medication dispensing data, hospitalisation and mortality data required for assessment of medication maintenance were obtained by individual linkage to routine national datasets as previously described.24 An encrypted version of the National Health Index Number (NHI), a unique identifier assigned to everyone who uses health and disability support services (>98% of the population),31 was used to anonymously link in-hospital ANZACS-QI patient records to the national datasets. Dispensing of cardiovascular medications was identified from the national Pharmaceutical Collection (PHARMS), which is jointly administered by the New Zealand Ministry of Health (MOH) and the Pharmaceutical Management Agency of New Zealand. PHARMS contains data regarding government-subsidised medications dispensed by community pharmacies nationwide, which encompasses statin medications relevant to these analyses.32 By 2009, 96% of dispensing episodes were reliably identifiable by NHI numbers. (S Ross, MOH, personal communication). ANZACS-QI validation in the national cohort has shown a high level of statin dispensing capture in PHARMS. In the 2015 to 2017 cohort, similar to the current study cohort, 95% of ACS patients were recorded as prescribed a statin in the ANZACS-QI registry and 93% were recorded as dispensed in PHARMS (unpublished data, manuscript in preparation).

Statistical analysis

Descriptive statistics for continuous variables were summarised as mean with standard deviation, median with inter-quartile range (IQR) and range. Categorical data are reported by frequency and percentage. For continuous variables, comparisons between groups were performed by the Student’s T-test. For categorical variables, Pearson’s chi-squared test was used.

Three multivariable log-binomial regression models were constructed to investigate the variables associated with (i) initial dispensing of 80mg atorvastatin, (ii) statin dose reduction by one year in those initially dispensed 80mg of statin post-discharge, and (iii) statin discontinuation by one year in those initially receiving any dose of statin. The relative risks (RRs) with accompanying 95% confidence intervals (CIs) of covariates were estimated. The covariates adjusted for were age, sex, ethnicity, smoker, diabetes, prior CVD, history of congestive heart failure (CHF), statin three months prior to admission, LDL-C level at baseline, coronary revascularisation, common concomitant medications, district health boards (DHB) and initial statin dose (model iii only).

All P-values reported were two tailed and a P-value <0.05 was considered significant. Data were analysed using SAS statistical package, version 9.4 (SAS Institute, Cary, NC).

Ethics

Linkage of the ANZACS-QI and national datasets has been approved by the National Multi Region Ethics Committee (MEC/07/19/EXP).

Results

The demographics, risk factors, clinical presentation and inpatient management for the 19,867 patient cohort are shown in Table 1. Overall, 92% of patients were dispensed a statin within the first three months post-discharge. Thirty-six percent of patients were dispensed 80mg atorvastatin and 43% “other high-intensity” statin dose, predominantly atorvastatin 40mg. Seventy-nine percent of patients were therefore dispensed high-intensity statins. There were a further 13% who received a low/medium dose and 8% received no statin.

Table 1: Characteristics according to statin dispensing.

ACS = Acute coronary syndrome; CABG = coronary artery bypass grafting; CAD = Coronary Artery Disease; CHF = Coronary Heart Failure; COPD = chronic obstructed pulmonary disease; CVD = Cardiovascular disease; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein-cholesterol; LMS = Left main STEMI; NSTEMI = Non ST elevation myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST elevation myocardial Infarction; VD = Vessel disease.

Those dispensed the maximal 80mg atorvastatin rather than another high-intensity dose were more likely to be younger, be men, be non-European, be current smokers and have an MI rather than unstable angina. They also had higher mean LDL-C, better renal function, more obstructive coronary artery disease and were more likely to have had coronary revascularisation by PCI or CABG. Similar variables differentiated those dispensed 80mg atorvastatin compared with a low/medium dose and no statin although the differences were more marked. Eigh percent of patients were discharged on a medication with the potential to interact with atorvastatin and although they were less likely than others to receive the 80mg dose nearly a quarter of these patients (n=384) were on the 80mg dose.

Who gets 80mg atorvastatin early post discharge? (Table 2, Figure 1)

On multivariable analysis, those who received the maximum 80mg dose of atorvastatin, as opposed to lower doses of statin, were more likely to be younger, male, smoke and have no history of CHF, normal renal function and coronary revascularisation. They were more likely to have been already on statin therapy and to have higher LDL-C cholesterol. Co-prescription of medications with known interactions with statin was also associated with lower use of 80mg atorvastatin.

There was wide variation in the use of the guidelines recommended atorvastatin 80mg dose between DHBs, with use ranging from 15% to 65% of patients. Even after adjustment for covariates, the RR for receiving 80mg statin ranged from as low as 0.29 (95% CIs, 0.22–0.39) to 1.05 (95% CIs, 0.96–1.15).

Table 2: Multivariable model for 80mg atorvastatin at discharge vs all other statin type and dose.

CHF = Congestive heart failure; CVD = Cardiovascular disease; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein-cholesterol.

Figure 1: Percentage of patients who receive high-dose statin at discharge in each district health board area. The high-intensity statin is subdivided into 80mg atorvastatin (dark bar) and other high intensity (lighter bar).

Dispensing of statin at one year post-discharge (See Table 3, Figure 2)

By one year after discharge, 625 (3.2%) of the study cohort had died leaving 19,242 in the one-year dispensing cohort. In the final quarter of the year post-discharge, 29.2% were dispensed atorvastatin 80mg, 35.7% “other high dose”, 14.1% a low/medium dose and 21.1% were not dispensed a statin. 70.5% of those discharged with atorvastatin 80mg continued that dose at one year. Only 14.2% of those initially on 80mg atorvastatin had a dose reduction. A similar number of patients initially dispensed atorvastatin 80mg and other high dose received no statin at one year. Only a small proportion of patients (6.2%) had statins started or dose up-titrated post-discharge.

Multivariable model predictors of high-dose statin maintenance and statin discontinuation by one year. (Appendix Table 1,2)

Table 3: Comparison of early vs one-year statin dispensing.

Other high dose = atorvastatin 40mg and simvastatin 80mg; low/medium dose = other doses of statins.

Figure 2: The distribution of statin dose prior to the index Acute Coronary Syndrome admission, early post-discharge and by one year post-discharge.

Low/medium dose = other doses of statins.

Who receives 80mg of atorvastatin by 1 year? (see Appendix Table 1)

On multivariable regression the strongest predictor of being dispensed 80mg of atorvastatin at one year was being discharged on that dose. Other variables independently associated with receiving 80mg of atorvastatin at one year were younger age, male sex, smoking at admission, being previously on a statin, undergoing revascularisation and having an eGFR ≥30ml/min/1.73m2.

Who discontinues statins? (Appendix Table 2)

After adjustment, the variables associated with statin discontinuation in those initially receiving any dose of statin at discharge were younger age, female sex, not having diabetes, prior CVD, no prior statin, initial low/medium dose, not receiving coronary revascularisation, eGFR<30ml/min/1.73m2 and a high baseline LDL-C. The risk of discontinuation did not differ for those started on atorvastatin 80mg compared with “other high-dose” statins.

Discussion

This study captured over 95% of New Zealand patients discharged after ACS in New Zealand who were actively managed with coronary angiography with or without revascularisation. A key pillar of management for these patients is optimal LDL-C management. We found that 79% were discharged with a high-intensity statin, although only 36% received the maximum, guidelines recommended 80mg dose of atorvastatin. By one year only 14% of those initially on 80mg were down-titrated to a lower dose, and the most important predictor of being on the maximum dose was being discharged on that dose. One in five patients were not dispensed a statin in the last three months of the year post-discharge. After adjustment, an initial 80mg atorvastatin dose and “other high dose” were both associated with a similar and lower risk of discontinuation compared with a low/medium-dose statin. In contrast to the low down-titration rates observed, only a small proportion of patients (6%) initially dispensed a dose less than the maximum atorvastatin dose or no statin had it up-titrated or commenced. Although the range across DHBs in use of high-intensity statin was modest at 73% to 87%, there was a much greater variation, from 15% to 65%, in the use of the 80mg atorvastatin dose. This variation persisted after adjustment for covariates suggesting that much of the variation may be due to local clinical preference.

Comparison with prior studies

The New Zealand utilisation of high-intensity statins is higher than in older registry data for ACS patients in 2003 and 2009 from the US, but this gap is not as large in more recent international reports. Those papers do not report the proportion on 80mg atorvastatin separately. Using the similar definitions for high-intensity statins, the older studies reported rates of prescribing or dispensing of high-intensity statin post ACS of approximately between only 23% and 38%.33–35 As in our study up-titration of doses post-discharge was also infrequent, with the discharge dose strongly associated with dose at one year.34 In a large US study of MI patients in 2014, 72% of those <65y and 57% of those over 65y were discharged on high-intensity statin.36 In a single centre in France in 2016, 61% of post-PCI patients were treated with high-intensity statin.37 We were also able to investigate the relationship between initial dose and discontinuation rates, and found no difference in discontinuation between the highest and “other high” doses. The highest rate of discontinuation was in those patients discharged on low/medium doses. This may reflect the characteristics of patients likely to receive a lower dose.

Atorvastatin 80mg vs other high dose—does it matter?

In the CTT meta-analysis,4 compared with less intensive regimens, more intensive regimens produced a highly significant 15% (p<0.0001) further reduction in major vascular events, consisting of significant reductions in coronary death or non-fatal myocardial infarction of 13% (p<0.0001), in coronary revascularisation of 19% (p<0.0001), and in ischaemic stroke of 16% (p=0.005). For each 1mmol/L reduction in LDL-C, total mortality was reduced by 10% over five years. Statins may also have anti-inflammatory and antioxidant effects beyond the effects of LDL-C lowering that may reduce events. There are no outcome studies, which randomised patients to receive atorvastatin 80mg vs 40mg. There are patients in whom it is clinically appropriate to use lower doses, particularly the very elderly (over 80 years), those with limited life expectancy and those on other medications known to interact with statins. Nevertheless the observed DHB variability after adjustment for covariates suggests that the choice of 40mg vs 80mg is strongly influenced by local clinical preference. By doubling the dose of a statin (atorvastatin 40mg to 80mg) it is expected that there will be a further 6% fall in LDL-C,35,38,39 and based on the well-established relationship between LDL-C lowering and outcomes greater use of 80mg dose would be expected to further improve outcomes.4

There may be an additional benefit of 80mg atorvastatin in patients undergoing PCI. In the recent Statins Evaluation in Coronary Procedures and Revascularization (SECUREPCI) Trial randomised, placebo-controlled trial, which assessed the impact of peri-procedural loading with atorvastatin [two loading doses of 80mg, before and 24h after planned PCI] at 30 days in 4,191 patients with ACS.40 All patients received atorvastatin 40mg per day starting 24h after the second loading dose. The authors found no significant treatment benefit in the overall study population but there was a significant 28% relative risk reduction in a composite of all-cause mortality, myocardial infarction, stroke and unplanned coronary revascularisation in patients who underwent PCI. The benefit was even more pronounced in STEMI patients undergoing primary PCI. These benefits will be offset by even a small increase in side effects if used inappropriately in patients at increased risk for side effects.14

Are we choosing the right patients for atorvastatin 80mg?

In our study there was no evidence, after adjustment for covariates including DHB of domicile, that patients were more likely to require a dose reduction after commencing 80mg compared with 40mg atorvastatin. In addition the 80mg dose was less likely to be used in patients co-administered a drug with a risk of drug-drug interaction. However, we have no more specific information about adverse side effects. It is noteworthy that there were significant numbers of patients on high-intensity statins in this cohort in whom guidelines recommend caution. This includes the very elderly where side effects may occur from over medication, those with severe chronic kidney and hepatic disease and patients on essential concomitant medications with a risk of drug-drug interaction. In the current study, 15% of those over 80 years, and nearly a quarter of the 8% of patients on concomitant medications with risk of drug interactions received the atorvastatin 80mg dose. Conversely, there were many patients without obvious reasons for caution who could potentially have been treated with a higher dose of statin.

Clinical implications

In the year post-ACS discharge, patients usually continue on the dose of statin they were discharged with, but nearly one in five patients initially dispensed statin were not dispensed a statin in the last three months of the year post-discharge. Because the maximum dispensing period in New Zealand is three months, this finding suggests sub-optimal maintenance or discontinuation of medication for those patients. It is therefore important that both the optimal dose be chosen for each patient in-hospital, and that patients then be supported to continue with their medication.

Choice of the appropriate statin dose is usually made in-hospital by the medical team, although in some cases, such as prior intolerance or abnormal liver function tests, up-titration as tolerated, from an initial low dose, may be done by the secondary and/or primary care teams after discharge. Supporting longer-term maintenance in ACS patients begins during the hospital admission and is supported by in-hospital and early post-discharge cardiac rehabilitation. In New Zealand it then continues under the supervision of the primary care team. Commencement and continuation of statins and other medications of proven clinical benefit which have been started in hospital requires optimal performance across this care continuum. Important components include:

1. Medical staff having access to evidence-based recommendations for medications and doses. In New Zealand initial medications post-ACS are often prescribed by junior medical staff who rotate through the coronary care unit and are under the supervision of multiple different cardiologists, which can result in variation in practice. Each unit should have a locally endorsed medication guideline which is regularly updated according to evolving evidence, and which is used by all medical team members. It should be based on national and international guidelines and give specific advice regarding recommended medications and doses which takes into account patient-specific factors including age, liver and renal function and concomitant medications. Although for many units this will be a paper-based guideline there is an increasing opportunity to incorporate this content within electronic prescribing systems, which can include a default list of medications and doses for each condition and provide advice/alerts as appropriate.

2. Involvement of the medical, nursing, cardiac rehabilitation team and pharmacists while the patient is in hospital, to both educate and support patients and their families regarding the benefits and potential risk of medications. The non-medical health professionals, if enabled to do so, also provide an important cross-check on medical prescribing decisions. Several New Zealand cardiology units now utilise the patient oriented “My Heart Recovery Plan”. This was developed in 2019 by the Health Quality and Safety Commission and ANZACS-QI, and it is endorsed for use nationally by the National Cardiac Network. It is a checklist designed to be used interactively by patients and their in-hospital medical, nursing and pharmacy team to support their understanding of their medications, the importance of continuing them long-term, whether they have been invited to cardiac rehabilitation, whether a follow-up appointment is arranged with their general practitioner and whether they need psychological support post-discharge. More widespread uptake and systematic implementation of this tool should be considered.

3. Practical considerations include simplifying the dosing regimen and encouraging patients to have their medications blister packed or a similar process which has been shown to improve adherence.41 Financial barriers do have an impact on adherence and these should be addressed.41 The default change per item dispensed in New Zealand is $5. Although there are programmes to reduce this for high-needs populations, our experience is that there are still patients who defer medications because of cost considerations.

4. Facilitation of referral to culturally appropriate cardiac rehabilitation programs after discharge to continue to educate and support patients and facilitate the transition to primary care.42

5. Primary care based self-monitoring and self-management programmes have proven effectiveness to improve medication adherence use, and utilising technology to ensure re-prescription of medication continues after discharge is a promising approach.41

6. Publication of data is an important way to feedback to clinicians and modify prescribing behavior.43 In particular, publication of the wide variation in use of the atorvastatin 80mg dose between DHBs is expected to prompt units to review their local guidelines. ANZACS-QI will continue to report back to the DHBs on high-intensity statin use as part of its annual Post-ACS Statin Adherence report to allow progress to be tracked.

Limitations

We used dispensing of statin as a marker of maintenance but not everyone who is dispensed a drug routinely is necessarily taking the medication. We had no other measures of adherence, nor did we have information about patient preferences. In some cases patients may be wary of high doses of a statin but accept a lower dose. Achieved LDL-C post discharge was not available for this study. The cohort comprised those patients who underwent invasive coronary angiography for whom we would expect intensive secondary prevention including high-intensity statins to be appropriate. The ANZACS-QI registry has very high rates of capture for these patients across New Zealand.44 Approximately 40% of patients with ACS do not receive coronary angiography and are not included in this analysis.45 However, of younger ACS patients between 60 and 70y, 70% receive an angiogram, and of those under 60y this increases to 80%.46 It is likely that use of high-intensity statin would be lower in those not receiving an angiogram given the high burden of comorbidity previously documented in such patients.45,47 No outcome data are presented and apart from medication discontinuation we cannot identify statin-specific side effects.

Conclusion

Only 36% of ACS patients who received invasive investigation post-ACS received guideline-recommended dose of 80mg atorvastatin. The dose of statin at hospital discharge is the most important determinant of dose by one year. The atorvastatin 80mg dose was not associated with higher discontinuation rates. Further optimisation of dosage at discharge by the secondary care team is feasible in New Zealand, for many clinically appropriate patients, and is an opportunity to achieve better long-term LDL-C reduction and thus improved clinical outcomes. GPs and primary care teams should have a greater role in medication up-titration, and systems need to be developed to ensure regular re-prescription of medication.

Appendix

Appendix Table 1: Multivariable regression analysis: variables associated with being dispensed 80mg atorvastatin at one year.

CHF = Congestive heart failure; CVD = Cardiovascular disease; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein-cholesterol.

Appendix Table 2: Multivariable regression analysis: variables associated with statin discontinuation by one year in patients initially dispensed statin.

CHF = Congestive heart failure; CVD = Cardiovascular disease; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein-cholesterol.

Summary

Abstract

Aim

A key pillar in the medical management of patients after an acute coronary syndrome (ACS) is the early initiation and maintenance of “high-intensity” statin therapy to lower low-density lipoprotein cholesterol (LDL-C) and to improve clinical outcomes. The aim of this study was to describe the New Zealand utilisation of high-intensity statin therapy in the first year post-ACS.

Method

19,867 New Zealand patients (≥20 years), discharged post-ACS event (2015–2017) were identified from the All New Zealand ACS Quality Improvement (ANZACS-QI) registry and anonymously linked with the national pharmaceutical dataset to identify statin dispensing early (0–3 months) and late (9–12 months) post-discharge. “High intensity” statin was subdivided into the New Zealand guidelines recommended dose (80mg atorvastatin) and “other high-intensity” statin (atorvastatin 40mg, simvastatin 80mg). All other statin doses were classified as “low/medium dose”.

Results

Seventy-nine percent were initially dispensed high-intensity statins. Thirty-six percent of the overall cohort received 80mg atorvastatin and 43% a lower “other high-intensity” statin. A further 13% received a medium/low dose and 8% no statin. By 12 months, 29% were dispensed atorvastatin 80mg, 36% another high dose, 14% a low/medium dose and 21% no statin. Only 14% of those initially on 80mg atorvastatin had a statin dose reduction. After multivariable adjustment, the risk of discontinuation was the same for those started on atorvastatin 80mg compared with “other high dose”, and lower than for those started on a low/medium dose. Few patients (6.2%) had statins started, or dose up-titrated post-discharge. There is clinically unexplained variation in the use of the highest atorvastatin 80mg dose between district health boards (range 15% to 65%).

Conclusion

Seventy-nine percent were initially dispensed high-intensity statins. Thirty-six percent of the overall cohort received 80mg atorvastatin and 43% a lower “other high-intensity” statin. A further 13% received a medium/low dose and 8% no statin. By 12 months, 29% were dispensed atorvastatin 80mg, 36% another high dose, 14% a low/medium dose and 21% no statin. Only 14% of those initially on 80mg atorvastatin had a statin dose reduction. After multivariable adjustment, the risk of discontinuation was the same for those started on atorvastatin 80mg compared with “other high dose”, and lower than for those started on a low/medium dose. Few patients (6.2%) had statins started, or dose up-titrated post-discharge. There is clinically unexplained variation in the use of the highest atorvastatin 80mg dose between district health boards (range 15% to 65%).

Author Information

Andrew J Kerr, Cardiologist, Counties Manukau District Health Board; Adjunct Associate Professor of Medicine, University of Auckland, Auckland; Sirisha Mitnala, Advanced Trainee in Cardiology, Counties Manukau District Health Board, Auckland; Mildred Lee, Biostatistician, Counties Manukau District Health Board, Auckland; Harvey D White, Cardiologist, Auckland City Hospital, Green Lane Cardiovascular Services, Auckland.

Acknowledgements

ANZACS-QI programme implementation, coordination and analysis: The ANZACS-QI software was developed and supported by Enigma Solutions. Programme implementation is coordinated by the National Institute for Health Innovation (NIHI) at the University of Auckland. The ANZACS-QI programme is funded by the New Zealand Ministry of Health. We thank the the National Health Board Analytic Services and Pharmac for enabling use of the national data sets. We also thank the VIEW team at the School of Population Health, University of Auckland for the curation and linkage of the national data. ANZACS-QI Governance group: Andrew Kerr (chair), Chris Nunn, Dean Boddington, Gary Sutcliffe, Gerry Devlin, Harvey White, John Edmond, Jonathon Tisch, Kim Marshall, Mayanna Lund, Michael Williams (deputy chair), Nick Fisher, Seif El Jack, Sue Riddle, Tony Scott. ANZACS-QI Project management: Kristin Sutherland (Project Manager), Charmaine Flynn (Northern Coordinator), Maxine Rhodes (Southern Coordinator), Anna-Marie Rattray (Research Assistant). Data analysis: Mildred Lee. Data management: Billy Wu (SOPH), Michelle Jenkins (NIHI), John Faatui (NIHI). We acknowledge all the New Zealand cardiologists, physicians, nursing staff and radiographers and all the patients who have supported and contributed to ANZACS-QI. ANZACS-QI hospital coordinators: Ascot Angiography: Summerscales, I. Money, J. Ashburton: Wilson, S. Auckland Hospital Belz, L. Stewart, R. Marshall, K. Bay of Islands: Cochran, G. Christchurch Hospital: Jackson, M. Sutherland, J. McLaren, S. Clutha Hospital: Reed, G. Campbell, B. McElrea, J. Dargaville: Cripps, J. Katipa, K. Dunedin Hospital: Foote, C. Dunstan: Nixon, G. Shaw, M. Klahn, R. Gisborne: Low, T. Gore: Lindley, G. Whitten, C. Grey Base Hospital: Smith, L. Jennings, M. Hawke’s Bay Hospital Soldiers Memorial: Brown, G. Grant, P. Hutt Hospital: Pinfold, S. Ferrier, K. Kitchen, R. Kaikoura Hospital: McCullough, C. Kaitaia Hospital: Thompson, R. Smith, N. Lakes District Hospital: Burt, J. Mercy Angiography: Shah, A. Ubod, B. Mercy Heart Centre: Hall, S. Middlemore: Mcintosh, R. McLachlan, A. Midland Cardiovascular Services: Phillips, K. Nelson Hospital: Besley, J. Abernethy, H. North Shore Hospital: Gray, L. Oamaru: Gonzales, R. Clare, L. Palmerston North Hospital: Kinloch, D. Rawene Hospital: Dorsay, C. Rotorua Hospital: Colby, C. Southland Hospital: Byers, R. Ghosh, P. St Georges Hospital: Lissette, J. Lewis, K. Taranaki Base Hospital: Ternouth, I. Spurway, M. Taumaranui: Pointon, L. Taupo Hospital: McAnanay, J. Tauranga Hospital: Goodson, J. Te Kuiti: Te Wano, T. Thames: Stutchbury, D. Timaru Hospital: Addidle, D. Tokoroa: Huitema, V. Waikato Hospital: Emerson, C. Pilay, R. Wairarapa Hospital: Matthews, T. Wairau Hospital: Langford, S. Ballagh, D. Waitakere Hospital: Long, L. Waitemata Hospital: Newcombe, R. Wakefield Private Hospital: Murphy, S. Wellington Hospital: Scott, B. Wylie, D. Whaktane Hospital: Bentley-Smith, M. Whanganui Hospital: Thompson, T. Whangarei Hospital: Vallancey, S.

Correspondence

Associate Professor Andrew Kerr, Department of Cardiology, Middlemore Hospital, Otahuhu, Auckland 93311.

Correspondence Email

andrew.kerr@middlemore.co.nz

Competing Interests

Dr White reports grants and personal fees from Eli Lilly and Company, personal fees and other from AstraZeneca, grants and personal fees from Omthera Pharmaceuticals, grants and personal fees from Pfizer USA, grants and personal fees from Eisai Inc., grants and personal fees from DalCor Pharma UK Inc., personal fees from Sirtex, personal fees from Acetelion, grants and personal fees from CSL Behring LLC, grants and personal fees from American Regent, grants and personal fees from Sanofi-Aventis Australia Pty Ltd, grants and personal fees from Esperion Therapeutics Inc., personal fees from Genentech Inc., grants and personal fees from Sanofi-Aventis, grants from National Heart, Lung and Blood Institute, outside the submitted work; Dr Kerr reports grants from HRC during the conduct of the study.

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24. Kerr A, Williams MJ, White H, et al. The All New Zealand Acute Coronary Syndrome Quality Improvement Programme: Implementation, Methodology and Cohorts (ANZACS-QI 9). New Zealand Medical Journal. 2016; 129:23–36.

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Contact diana@nzma.org.nz
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Acute coronary syndrome (ACS) is one of the leading causes of death in New Zealand and worldwide. Over 15,000 patients are admitted to New Zealand hospitals with an acute coronary syndrome (ACS) every year and the one-year case fatality is 20%.1 LDL lowering using 3-hydroxy-3-methyl-glutaryl-CoA (HMGCoA) inhibitors (statins) following an acute coronary syndrome has been shown to reduce the risk of heart attack, stroke and all-cause mortality.2 Trials of higher-dose statin therapy compared with lower-dose therapy have been demonstrated to further reduce major vascular events in patients with ACS or stable coronary artery disease.3,4 The early period following an ACS is a critical stage of coronary heart disease; with a high risk of recurrent events and death. The early initiation and maintenance of “high-intensity” statin after ACS is recommended for all patients without contraindications, regardless of initial low density lipoprotein-C (LDL-C) values.5–14 This recommendation comes with the proviso that the use of lower-intensity statin therapy should be considered in patients at increased risk of adverse effects with high-intensity statin therapy, such as in the elderly, patients diagnosed with hepatic or renal impairment, or in the case of a potential risk of drug-drug interactions with other essential concomitant therapies. Prior studies report that only two-thirds of patients who present with an ACS are maintained on a statin at one year15 and three years’16 post-discharge. But to date, no studies have reported the use of high-intensity therapy in New Zealand post-ACS.

“High-intensity” has been variously defined by either the type of statin/dose used in the randomised controlled clinical trials or by the pharmacological effects of statin type/dose on mean LDL-C levels. While the American College of Cardiology/American Heart Association (ACC/AHA) definition of high-intensity statin is based on statin/type and dose,11 the European Society of Cardiology (ESC) definition includes any statin type/dose which can reduce mean LDL by 50%.17 However, in the ESC guideline, data is presented showing the statin type/doses which achieve this LDL reduction, which align well with the ACC/AHA definition. Three of the five more intense versus less intense clinical trials used 80mg of atorvastatin in the “high-intensity” arm,18–20 which lowers LDL-C by approximately 50%.14 Two trials used simvastatin 80mg as the more intense statin arm,21,22 a dose which is no longer recommended due to an excess of myositis, and has a Food and Drug Administration (FDA) black box warning not to prescribe this dose of simvastatin. In one trial a small percentage received atorvastatin 40mg20 and this dose has been included within the ESC and AHA/ACC “high-intensity” statin definition.11,17 Moderate low/medium doses are expected to reduce LDL-C by 30–50%.

Since 2015 the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry has captured data on over 95% of New Zealand patients hospitalised for ACS who underwent coronary angiography. By linking ANZACS-QI registry data to national routine datasets, both initial statin dispensing (type and dose), and subsequent maintenance, can be tracked.23

The aim of this study is therefore to describe the contemporary New Zealand use of high-intensity statin therapy after discharge post-ACS, its maintenance in the first year and the determinants of high-dose statin maintenance at one year.

Methods

Cohort

New Zealand residents (aged over 20y) hospitalised with ACS between 1 Jan 2015 to 31 Dec 2017 and who underwent coronary angiography were identified from the ANZACS-QI registry. Only patients who were alive 30 days after discharge were included to ensure the completeness of early dispensing data. Only the first presentation per person in the three-year period was included.

The ANZACS-QI registry is a web-based electronic database that captures a mandatory dataset in ACS patients who underwent a coronary angiogram, which includes patient demographics, admission ACS risk stratification, cardiovascular risk factors, investigations and management, inpatient outcomes and medications prescribed at discharge. Details regarding the ANZACS-QI programme and registry data collection have been previously reported.24 The registry is subject to monthly auditing to ensure capture of >95% of all patients admitted with suspected ACS who are investigated with coronary angiography, and annual audit to check the accuracy of data entry.

Definitions

ACS included myocardial infarction (MI) or unstable angina. MI was defined according to the contemporary universal definition.25 Variables used for this study included age, sex, ethnicity, prior statin use, diabetes, smoking status, history of cardiovascular disease (CVD), coronary intervention (coronary artery bypass grafting (CABG)) or percutaneous coronary intervention (PCI) and a global estimate of in-hospital mortality post-ACS (the Global Registry of ACS (GRACE) score).26 The GRACE score is reported categorically as low (<1%), medium (1 to <3%) or high (>=3%) as recommended by the ESC. History of CVD was defined as a diagnosis, prior to the current event, of MI/angina, stroke/TIA, peripheral vascular disease or prior radiological evidence of vascular disease. PCI/CABG Sociodemographic variables and residency status were derived from the linked national dataset. For patients in whom more than one ethnic group was recorded, ethnicity was prioritised, in accordance with health sector protocols, in the following order: indigenous Māori, Pacific, Indian and New Zealand European/Other (NZEO).27 Socioeconomic deprivation was assessed by the NZDep13 score,28 a census-based small area 10-point index of deprivation based on the person’s domicile. Prior statin use was derived from the national pharmaceutical claims dataset and was defined as having a statin dispensed during the 90-day period prior to index admission. Concomitant medications dispensed at discharge which should be used with caution in combination with statins were also identified. Because most high-dose statin use was with atorvastatin, we have reported the co-dispensing of medications identified as having a potentially major interaction with that agent.29,30 This group comprises cyclosporin, diltiazem, verapamil, digoxin, erythromycin, clarithromycin, gemfibrozil, ketoconazole, itraconazole and ritonavir.

Statin dispensing analysis

Statin type and dose dispensing were obtained early (within three months of hospital discharge) and late after discharge (in the last three months of the year after discharge) using anonymised linkage to the national pharmaceuticals dataset in order to identify and describe the patients who were initiated on high-dose statins, and those who were maintained on maximum-dose statins at one year.

“High-intensity statin” was defined according to the ACC/AHA definition.11 In New Zealand this comprises atorvastatin 40mg or 80mg, or simvastatin 80mg. For this analysis we chose to divide “high intensity” into the clinical trial high-intensity dose of 80mg atorvastatin recommended in the New Zealand guidelines6,7 and “other high-intensity” statin (atorvastatin 40mg, simvastatin 80mg). Rosuvastatin is not publicly funded in New Zealand so use is very low. All other statin type/doses combinations were considered low/medium dose.

Data linkage

Medication dispensing data, hospitalisation and mortality data required for assessment of medication maintenance were obtained by individual linkage to routine national datasets as previously described.24 An encrypted version of the National Health Index Number (NHI), a unique identifier assigned to everyone who uses health and disability support services (>98% of the population),31 was used to anonymously link in-hospital ANZACS-QI patient records to the national datasets. Dispensing of cardiovascular medications was identified from the national Pharmaceutical Collection (PHARMS), which is jointly administered by the New Zealand Ministry of Health (MOH) and the Pharmaceutical Management Agency of New Zealand. PHARMS contains data regarding government-subsidised medications dispensed by community pharmacies nationwide, which encompasses statin medications relevant to these analyses.32 By 2009, 96% of dispensing episodes were reliably identifiable by NHI numbers. (S Ross, MOH, personal communication). ANZACS-QI validation in the national cohort has shown a high level of statin dispensing capture in PHARMS. In the 2015 to 2017 cohort, similar to the current study cohort, 95% of ACS patients were recorded as prescribed a statin in the ANZACS-QI registry and 93% were recorded as dispensed in PHARMS (unpublished data, manuscript in preparation).

Statistical analysis

Descriptive statistics for continuous variables were summarised as mean with standard deviation, median with inter-quartile range (IQR) and range. Categorical data are reported by frequency and percentage. For continuous variables, comparisons between groups were performed by the Student’s T-test. For categorical variables, Pearson’s chi-squared test was used.

Three multivariable log-binomial regression models were constructed to investigate the variables associated with (i) initial dispensing of 80mg atorvastatin, (ii) statin dose reduction by one year in those initially dispensed 80mg of statin post-discharge, and (iii) statin discontinuation by one year in those initially receiving any dose of statin. The relative risks (RRs) with accompanying 95% confidence intervals (CIs) of covariates were estimated. The covariates adjusted for were age, sex, ethnicity, smoker, diabetes, prior CVD, history of congestive heart failure (CHF), statin three months prior to admission, LDL-C level at baseline, coronary revascularisation, common concomitant medications, district health boards (DHB) and initial statin dose (model iii only).

All P-values reported were two tailed and a P-value <0.05 was considered significant. Data were analysed using SAS statistical package, version 9.4 (SAS Institute, Cary, NC).

Ethics

Linkage of the ANZACS-QI and national datasets has been approved by the National Multi Region Ethics Committee (MEC/07/19/EXP).

Results

The demographics, risk factors, clinical presentation and inpatient management for the 19,867 patient cohort are shown in Table 1. Overall, 92% of patients were dispensed a statin within the first three months post-discharge. Thirty-six percent of patients were dispensed 80mg atorvastatin and 43% “other high-intensity” statin dose, predominantly atorvastatin 40mg. Seventy-nine percent of patients were therefore dispensed high-intensity statins. There were a further 13% who received a low/medium dose and 8% received no statin.

Table 1: Characteristics according to statin dispensing.

ACS = Acute coronary syndrome; CABG = coronary artery bypass grafting; CAD = Coronary Artery Disease; CHF = Coronary Heart Failure; COPD = chronic obstructed pulmonary disease; CVD = Cardiovascular disease; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein-cholesterol; LMS = Left main STEMI; NSTEMI = Non ST elevation myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST elevation myocardial Infarction; VD = Vessel disease.

Those dispensed the maximal 80mg atorvastatin rather than another high-intensity dose were more likely to be younger, be men, be non-European, be current smokers and have an MI rather than unstable angina. They also had higher mean LDL-C, better renal function, more obstructive coronary artery disease and were more likely to have had coronary revascularisation by PCI or CABG. Similar variables differentiated those dispensed 80mg atorvastatin compared with a low/medium dose and no statin although the differences were more marked. Eigh percent of patients were discharged on a medication with the potential to interact with atorvastatin and although they were less likely than others to receive the 80mg dose nearly a quarter of these patients (n=384) were on the 80mg dose.

Who gets 80mg atorvastatin early post discharge? (Table 2, Figure 1)

On multivariable analysis, those who received the maximum 80mg dose of atorvastatin, as opposed to lower doses of statin, were more likely to be younger, male, smoke and have no history of CHF, normal renal function and coronary revascularisation. They were more likely to have been already on statin therapy and to have higher LDL-C cholesterol. Co-prescription of medications with known interactions with statin was also associated with lower use of 80mg atorvastatin.

There was wide variation in the use of the guidelines recommended atorvastatin 80mg dose between DHBs, with use ranging from 15% to 65% of patients. Even after adjustment for covariates, the RR for receiving 80mg statin ranged from as low as 0.29 (95% CIs, 0.22–0.39) to 1.05 (95% CIs, 0.96–1.15).

Table 2: Multivariable model for 80mg atorvastatin at discharge vs all other statin type and dose.

CHF = Congestive heart failure; CVD = Cardiovascular disease; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein-cholesterol.

Figure 1: Percentage of patients who receive high-dose statin at discharge in each district health board area. The high-intensity statin is subdivided into 80mg atorvastatin (dark bar) and other high intensity (lighter bar).

Dispensing of statin at one year post-discharge (See Table 3, Figure 2)

By one year after discharge, 625 (3.2%) of the study cohort had died leaving 19,242 in the one-year dispensing cohort. In the final quarter of the year post-discharge, 29.2% were dispensed atorvastatin 80mg, 35.7% “other high dose”, 14.1% a low/medium dose and 21.1% were not dispensed a statin. 70.5% of those discharged with atorvastatin 80mg continued that dose at one year. Only 14.2% of those initially on 80mg atorvastatin had a dose reduction. A similar number of patients initially dispensed atorvastatin 80mg and other high dose received no statin at one year. Only a small proportion of patients (6.2%) had statins started or dose up-titrated post-discharge.

Multivariable model predictors of high-dose statin maintenance and statin discontinuation by one year. (Appendix Table 1,2)

Table 3: Comparison of early vs one-year statin dispensing.

Other high dose = atorvastatin 40mg and simvastatin 80mg; low/medium dose = other doses of statins.

Figure 2: The distribution of statin dose prior to the index Acute Coronary Syndrome admission, early post-discharge and by one year post-discharge.

Low/medium dose = other doses of statins.

Who receives 80mg of atorvastatin by 1 year? (see Appendix Table 1)

On multivariable regression the strongest predictor of being dispensed 80mg of atorvastatin at one year was being discharged on that dose. Other variables independently associated with receiving 80mg of atorvastatin at one year were younger age, male sex, smoking at admission, being previously on a statin, undergoing revascularisation and having an eGFR ≥30ml/min/1.73m2.

Who discontinues statins? (Appendix Table 2)

After adjustment, the variables associated with statin discontinuation in those initially receiving any dose of statin at discharge were younger age, female sex, not having diabetes, prior CVD, no prior statin, initial low/medium dose, not receiving coronary revascularisation, eGFR<30ml/min/1.73m2 and a high baseline LDL-C. The risk of discontinuation did not differ for those started on atorvastatin 80mg compared with “other high-dose” statins.

Discussion

This study captured over 95% of New Zealand patients discharged after ACS in New Zealand who were actively managed with coronary angiography with or without revascularisation. A key pillar of management for these patients is optimal LDL-C management. We found that 79% were discharged with a high-intensity statin, although only 36% received the maximum, guidelines recommended 80mg dose of atorvastatin. By one year only 14% of those initially on 80mg were down-titrated to a lower dose, and the most important predictor of being on the maximum dose was being discharged on that dose. One in five patients were not dispensed a statin in the last three months of the year post-discharge. After adjustment, an initial 80mg atorvastatin dose and “other high dose” were both associated with a similar and lower risk of discontinuation compared with a low/medium-dose statin. In contrast to the low down-titration rates observed, only a small proportion of patients (6%) initially dispensed a dose less than the maximum atorvastatin dose or no statin had it up-titrated or commenced. Although the range across DHBs in use of high-intensity statin was modest at 73% to 87%, there was a much greater variation, from 15% to 65%, in the use of the 80mg atorvastatin dose. This variation persisted after adjustment for covariates suggesting that much of the variation may be due to local clinical preference.

Comparison with prior studies

The New Zealand utilisation of high-intensity statins is higher than in older registry data for ACS patients in 2003 and 2009 from the US, but this gap is not as large in more recent international reports. Those papers do not report the proportion on 80mg atorvastatin separately. Using the similar definitions for high-intensity statins, the older studies reported rates of prescribing or dispensing of high-intensity statin post ACS of approximately between only 23% and 38%.33–35 As in our study up-titration of doses post-discharge was also infrequent, with the discharge dose strongly associated with dose at one year.34 In a large US study of MI patients in 2014, 72% of those <65y and 57% of those over 65y were discharged on high-intensity statin.36 In a single centre in France in 2016, 61% of post-PCI patients were treated with high-intensity statin.37 We were also able to investigate the relationship between initial dose and discontinuation rates, and found no difference in discontinuation between the highest and “other high” doses. The highest rate of discontinuation was in those patients discharged on low/medium doses. This may reflect the characteristics of patients likely to receive a lower dose.

Atorvastatin 80mg vs other high dose—does it matter?

In the CTT meta-analysis,4 compared with less intensive regimens, more intensive regimens produced a highly significant 15% (p<0.0001) further reduction in major vascular events, consisting of significant reductions in coronary death or non-fatal myocardial infarction of 13% (p<0.0001), in coronary revascularisation of 19% (p<0.0001), and in ischaemic stroke of 16% (p=0.005). For each 1mmol/L reduction in LDL-C, total mortality was reduced by 10% over five years. Statins may also have anti-inflammatory and antioxidant effects beyond the effects of LDL-C lowering that may reduce events. There are no outcome studies, which randomised patients to receive atorvastatin 80mg vs 40mg. There are patients in whom it is clinically appropriate to use lower doses, particularly the very elderly (over 80 years), those with limited life expectancy and those on other medications known to interact with statins. Nevertheless the observed DHB variability after adjustment for covariates suggests that the choice of 40mg vs 80mg is strongly influenced by local clinical preference. By doubling the dose of a statin (atorvastatin 40mg to 80mg) it is expected that there will be a further 6% fall in LDL-C,35,38,39 and based on the well-established relationship between LDL-C lowering and outcomes greater use of 80mg dose would be expected to further improve outcomes.4

There may be an additional benefit of 80mg atorvastatin in patients undergoing PCI. In the recent Statins Evaluation in Coronary Procedures and Revascularization (SECUREPCI) Trial randomised, placebo-controlled trial, which assessed the impact of peri-procedural loading with atorvastatin [two loading doses of 80mg, before and 24h after planned PCI] at 30 days in 4,191 patients with ACS.40 All patients received atorvastatin 40mg per day starting 24h after the second loading dose. The authors found no significant treatment benefit in the overall study population but there was a significant 28% relative risk reduction in a composite of all-cause mortality, myocardial infarction, stroke and unplanned coronary revascularisation in patients who underwent PCI. The benefit was even more pronounced in STEMI patients undergoing primary PCI. These benefits will be offset by even a small increase in side effects if used inappropriately in patients at increased risk for side effects.14

Are we choosing the right patients for atorvastatin 80mg?

In our study there was no evidence, after adjustment for covariates including DHB of domicile, that patients were more likely to require a dose reduction after commencing 80mg compared with 40mg atorvastatin. In addition the 80mg dose was less likely to be used in patients co-administered a drug with a risk of drug-drug interaction. However, we have no more specific information about adverse side effects. It is noteworthy that there were significant numbers of patients on high-intensity statins in this cohort in whom guidelines recommend caution. This includes the very elderly where side effects may occur from over medication, those with severe chronic kidney and hepatic disease and patients on essential concomitant medications with a risk of drug-drug interaction. In the current study, 15% of those over 80 years, and nearly a quarter of the 8% of patients on concomitant medications with risk of drug interactions received the atorvastatin 80mg dose. Conversely, there were many patients without obvious reasons for caution who could potentially have been treated with a higher dose of statin.

Clinical implications

In the year post-ACS discharge, patients usually continue on the dose of statin they were discharged with, but nearly one in five patients initially dispensed statin were not dispensed a statin in the last three months of the year post-discharge. Because the maximum dispensing period in New Zealand is three months, this finding suggests sub-optimal maintenance or discontinuation of medication for those patients. It is therefore important that both the optimal dose be chosen for each patient in-hospital, and that patients then be supported to continue with their medication.

Choice of the appropriate statin dose is usually made in-hospital by the medical team, although in some cases, such as prior intolerance or abnormal liver function tests, up-titration as tolerated, from an initial low dose, may be done by the secondary and/or primary care teams after discharge. Supporting longer-term maintenance in ACS patients begins during the hospital admission and is supported by in-hospital and early post-discharge cardiac rehabilitation. In New Zealand it then continues under the supervision of the primary care team. Commencement and continuation of statins and other medications of proven clinical benefit which have been started in hospital requires optimal performance across this care continuum. Important components include:

1. Medical staff having access to evidence-based recommendations for medications and doses. In New Zealand initial medications post-ACS are often prescribed by junior medical staff who rotate through the coronary care unit and are under the supervision of multiple different cardiologists, which can result in variation in practice. Each unit should have a locally endorsed medication guideline which is regularly updated according to evolving evidence, and which is used by all medical team members. It should be based on national and international guidelines and give specific advice regarding recommended medications and doses which takes into account patient-specific factors including age, liver and renal function and concomitant medications. Although for many units this will be a paper-based guideline there is an increasing opportunity to incorporate this content within electronic prescribing systems, which can include a default list of medications and doses for each condition and provide advice/alerts as appropriate.

2. Involvement of the medical, nursing, cardiac rehabilitation team and pharmacists while the patient is in hospital, to both educate and support patients and their families regarding the benefits and potential risk of medications. The non-medical health professionals, if enabled to do so, also provide an important cross-check on medical prescribing decisions. Several New Zealand cardiology units now utilise the patient oriented “My Heart Recovery Plan”. This was developed in 2019 by the Health Quality and Safety Commission and ANZACS-QI, and it is endorsed for use nationally by the National Cardiac Network. It is a checklist designed to be used interactively by patients and their in-hospital medical, nursing and pharmacy team to support their understanding of their medications, the importance of continuing them long-term, whether they have been invited to cardiac rehabilitation, whether a follow-up appointment is arranged with their general practitioner and whether they need psychological support post-discharge. More widespread uptake and systematic implementation of this tool should be considered.

3. Practical considerations include simplifying the dosing regimen and encouraging patients to have their medications blister packed or a similar process which has been shown to improve adherence.41 Financial barriers do have an impact on adherence and these should be addressed.41 The default change per item dispensed in New Zealand is $5. Although there are programmes to reduce this for high-needs populations, our experience is that there are still patients who defer medications because of cost considerations.

4. Facilitation of referral to culturally appropriate cardiac rehabilitation programs after discharge to continue to educate and support patients and facilitate the transition to primary care.42

5. Primary care based self-monitoring and self-management programmes have proven effectiveness to improve medication adherence use, and utilising technology to ensure re-prescription of medication continues after discharge is a promising approach.41

6. Publication of data is an important way to feedback to clinicians and modify prescribing behavior.43 In particular, publication of the wide variation in use of the atorvastatin 80mg dose between DHBs is expected to prompt units to review their local guidelines. ANZACS-QI will continue to report back to the DHBs on high-intensity statin use as part of its annual Post-ACS Statin Adherence report to allow progress to be tracked.

Limitations

We used dispensing of statin as a marker of maintenance but not everyone who is dispensed a drug routinely is necessarily taking the medication. We had no other measures of adherence, nor did we have information about patient preferences. In some cases patients may be wary of high doses of a statin but accept a lower dose. Achieved LDL-C post discharge was not available for this study. The cohort comprised those patients who underwent invasive coronary angiography for whom we would expect intensive secondary prevention including high-intensity statins to be appropriate. The ANZACS-QI registry has very high rates of capture for these patients across New Zealand.44 Approximately 40% of patients with ACS do not receive coronary angiography and are not included in this analysis.45 However, of younger ACS patients between 60 and 70y, 70% receive an angiogram, and of those under 60y this increases to 80%.46 It is likely that use of high-intensity statin would be lower in those not receiving an angiogram given the high burden of comorbidity previously documented in such patients.45,47 No outcome data are presented and apart from medication discontinuation we cannot identify statin-specific side effects.

Conclusion

Only 36% of ACS patients who received invasive investigation post-ACS received guideline-recommended dose of 80mg atorvastatin. The dose of statin at hospital discharge is the most important determinant of dose by one year. The atorvastatin 80mg dose was not associated with higher discontinuation rates. Further optimisation of dosage at discharge by the secondary care team is feasible in New Zealand, for many clinically appropriate patients, and is an opportunity to achieve better long-term LDL-C reduction and thus improved clinical outcomes. GPs and primary care teams should have a greater role in medication up-titration, and systems need to be developed to ensure regular re-prescription of medication.

Appendix

Appendix Table 1: Multivariable regression analysis: variables associated with being dispensed 80mg atorvastatin at one year.

CHF = Congestive heart failure; CVD = Cardiovascular disease; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein-cholesterol.

Appendix Table 2: Multivariable regression analysis: variables associated with statin discontinuation by one year in patients initially dispensed statin.

CHF = Congestive heart failure; CVD = Cardiovascular disease; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein-cholesterol.

Summary

Abstract

Aim

A key pillar in the medical management of patients after an acute coronary syndrome (ACS) is the early initiation and maintenance of “high-intensity” statin therapy to lower low-density lipoprotein cholesterol (LDL-C) and to improve clinical outcomes. The aim of this study was to describe the New Zealand utilisation of high-intensity statin therapy in the first year post-ACS.

Method

19,867 New Zealand patients (≥20 years), discharged post-ACS event (2015–2017) were identified from the All New Zealand ACS Quality Improvement (ANZACS-QI) registry and anonymously linked with the national pharmaceutical dataset to identify statin dispensing early (0–3 months) and late (9–12 months) post-discharge. “High intensity” statin was subdivided into the New Zealand guidelines recommended dose (80mg atorvastatin) and “other high-intensity” statin (atorvastatin 40mg, simvastatin 80mg). All other statin doses were classified as “low/medium dose”.

Results

Seventy-nine percent were initially dispensed high-intensity statins. Thirty-six percent of the overall cohort received 80mg atorvastatin and 43% a lower “other high-intensity” statin. A further 13% received a medium/low dose and 8% no statin. By 12 months, 29% were dispensed atorvastatin 80mg, 36% another high dose, 14% a low/medium dose and 21% no statin. Only 14% of those initially on 80mg atorvastatin had a statin dose reduction. After multivariable adjustment, the risk of discontinuation was the same for those started on atorvastatin 80mg compared with “other high dose”, and lower than for those started on a low/medium dose. Few patients (6.2%) had statins started, or dose up-titrated post-discharge. There is clinically unexplained variation in the use of the highest atorvastatin 80mg dose between district health boards (range 15% to 65%).

Conclusion

Seventy-nine percent were initially dispensed high-intensity statins. Thirty-six percent of the overall cohort received 80mg atorvastatin and 43% a lower “other high-intensity” statin. A further 13% received a medium/low dose and 8% no statin. By 12 months, 29% were dispensed atorvastatin 80mg, 36% another high dose, 14% a low/medium dose and 21% no statin. Only 14% of those initially on 80mg atorvastatin had a statin dose reduction. After multivariable adjustment, the risk of discontinuation was the same for those started on atorvastatin 80mg compared with “other high dose”, and lower than for those started on a low/medium dose. Few patients (6.2%) had statins started, or dose up-titrated post-discharge. There is clinically unexplained variation in the use of the highest atorvastatin 80mg dose between district health boards (range 15% to 65%).

Author Information

Andrew J Kerr, Cardiologist, Counties Manukau District Health Board; Adjunct Associate Professor of Medicine, University of Auckland, Auckland; Sirisha Mitnala, Advanced Trainee in Cardiology, Counties Manukau District Health Board, Auckland; Mildred Lee, Biostatistician, Counties Manukau District Health Board, Auckland; Harvey D White, Cardiologist, Auckland City Hospital, Green Lane Cardiovascular Services, Auckland.

Acknowledgements

ANZACS-QI programme implementation, coordination and analysis: The ANZACS-QI software was developed and supported by Enigma Solutions. Programme implementation is coordinated by the National Institute for Health Innovation (NIHI) at the University of Auckland. The ANZACS-QI programme is funded by the New Zealand Ministry of Health. We thank the the National Health Board Analytic Services and Pharmac for enabling use of the national data sets. We also thank the VIEW team at the School of Population Health, University of Auckland for the curation and linkage of the national data. ANZACS-QI Governance group: Andrew Kerr (chair), Chris Nunn, Dean Boddington, Gary Sutcliffe, Gerry Devlin, Harvey White, John Edmond, Jonathon Tisch, Kim Marshall, Mayanna Lund, Michael Williams (deputy chair), Nick Fisher, Seif El Jack, Sue Riddle, Tony Scott. ANZACS-QI Project management: Kristin Sutherland (Project Manager), Charmaine Flynn (Northern Coordinator), Maxine Rhodes (Southern Coordinator), Anna-Marie Rattray (Research Assistant). Data analysis: Mildred Lee. Data management: Billy Wu (SOPH), Michelle Jenkins (NIHI), John Faatui (NIHI). We acknowledge all the New Zealand cardiologists, physicians, nursing staff and radiographers and all the patients who have supported and contributed to ANZACS-QI. ANZACS-QI hospital coordinators: Ascot Angiography: Summerscales, I. Money, J. Ashburton: Wilson, S. Auckland Hospital Belz, L. Stewart, R. Marshall, K. Bay of Islands: Cochran, G. Christchurch Hospital: Jackson, M. Sutherland, J. McLaren, S. Clutha Hospital: Reed, G. Campbell, B. McElrea, J. Dargaville: Cripps, J. Katipa, K. Dunedin Hospital: Foote, C. Dunstan: Nixon, G. Shaw, M. Klahn, R. Gisborne: Low, T. Gore: Lindley, G. Whitten, C. Grey Base Hospital: Smith, L. Jennings, M. Hawke’s Bay Hospital Soldiers Memorial: Brown, G. Grant, P. Hutt Hospital: Pinfold, S. Ferrier, K. Kitchen, R. Kaikoura Hospital: McCullough, C. Kaitaia Hospital: Thompson, R. Smith, N. Lakes District Hospital: Burt, J. Mercy Angiography: Shah, A. Ubod, B. Mercy Heart Centre: Hall, S. Middlemore: Mcintosh, R. McLachlan, A. Midland Cardiovascular Services: Phillips, K. Nelson Hospital: Besley, J. Abernethy, H. North Shore Hospital: Gray, L. Oamaru: Gonzales, R. Clare, L. Palmerston North Hospital: Kinloch, D. Rawene Hospital: Dorsay, C. Rotorua Hospital: Colby, C. Southland Hospital: Byers, R. Ghosh, P. St Georges Hospital: Lissette, J. Lewis, K. Taranaki Base Hospital: Ternouth, I. Spurway, M. Taumaranui: Pointon, L. Taupo Hospital: McAnanay, J. Tauranga Hospital: Goodson, J. Te Kuiti: Te Wano, T. Thames: Stutchbury, D. Timaru Hospital: Addidle, D. Tokoroa: Huitema, V. Waikato Hospital: Emerson, C. Pilay, R. Wairarapa Hospital: Matthews, T. Wairau Hospital: Langford, S. Ballagh, D. Waitakere Hospital: Long, L. Waitemata Hospital: Newcombe, R. Wakefield Private Hospital: Murphy, S. Wellington Hospital: Scott, B. Wylie, D. Whaktane Hospital: Bentley-Smith, M. Whanganui Hospital: Thompson, T. Whangarei Hospital: Vallancey, S.

Correspondence

Associate Professor Andrew Kerr, Department of Cardiology, Middlemore Hospital, Otahuhu, Auckland 93311.

Correspondence Email

andrew.kerr@middlemore.co.nz

Competing Interests

Dr White reports grants and personal fees from Eli Lilly and Company, personal fees and other from AstraZeneca, grants and personal fees from Omthera Pharmaceuticals, grants and personal fees from Pfizer USA, grants and personal fees from Eisai Inc., grants and personal fees from DalCor Pharma UK Inc., personal fees from Sirtex, personal fees from Acetelion, grants and personal fees from CSL Behring LLC, grants and personal fees from American Regent, grants and personal fees from Sanofi-Aventis Australia Pty Ltd, grants and personal fees from Esperion Therapeutics Inc., personal fees from Genentech Inc., grants and personal fees from Sanofi-Aventis, grants from National Heart, Lung and Blood Institute, outside the submitted work; Dr Kerr reports grants from HRC during the conduct of the study.

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