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| Journal of the New Zealand Medical Association,
07-October-2005, Vol 118 No 1223
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Use of evidence-based management for acute coronary
syndrome
Eng Wei Tang, Cheuk-Kit Wong, Gerard Wilkins, Peter
Herbison, Michael Williams, Patrick Kay, Norma Restieaux
Findings from major clinical trials constitute the basis for
evidence-based management (EBM) of acute coronary syndrome (ACS) which are
summarised by various professional bodies to produce official treatment
guidelines.1,2 Data from international Registries often revealed significant
differences between published guidelines and real life clinical practice in
managing ACS.3,4
Our study aims to compare our local practice in Dunedin
Hospital in the years 2001–2002 with what was published in:
MethodsPatient
identification—We identified (retrospectively) all consecutive
patients admitted into Coronary Care in Dunedin Hospital from 1 January 2001 to
31 December 2002 with ACS. Relevant information was extracted from clinical
notes. All patients had ACS as their discharge diagnosis and were above 18 years
of age. Patients were excluded if the ACS was precipitated or accompanied by
morbid conditions such as sepsis, trauma, or major surgery. Our Coronary Care
Unit acted also as a tertiary referral centre for Oamaru Hospital, Dunstan
Hospital, Kew Hospital (in Invercargill), and Lakes District Health (in
Queenstown) with a catchment area including both Otago and Southland (population
286,700; June 2003).9
Data
collection—A systematic approach was made to collect data on
demographic characteristics, presenting symptoms, medical history, inpatient
management, treatment, and inpatient outcome.
ACS was divided into
Statistical
analysis—Statistical analysis was prepared on SPSS for Macintosh
Version 10. Data are presented as mean ± standard deviation or proportions
as appropriate. Chi-squared tests were used to compare proportions. The test was
double-sided and considered to be statistically significant at
α<0.05.
Definition of other
analysed parameters—The diagnosis of diabetes was recorded based on
the patient’s history. Dyslipidaemia was defined as total fasting
cholesterol of ≥5.5 mmol/L measured during the index admission. Left
ventricular ejection function (EF) was assessed semi-quantitatively by
echocardiography or left ventriculography during cardiac catheterisation and was
classified as normal (EF≥50%), mildly impaired (EF=35–49%),
moderately impaired (EF=25–34%) or severely impaired (EF<25%). Heart
failure was recorded if the attending cardiologist had made the diagnosis, if
there was radiographic evidence of pulmonary congestion, or if a loop diuretic
was commenced during hospitalisation.
ResultsIn 2001–2002, 815 patients were admitted into Coronary
Care, of which 577 satisfied our inclusion criteria. Table 1 shows the
demographics of the 577 patients in this study (195 with STEMI, 239 with NSTEMI,
and 143 with unstable angina).
Pharmacological management
of ACS—Table 2 showed the use of aspirin, beta-blockers, statins,
and ACE inhibitors.
In the 577 ACS patients, 98%, 80%, and 70% were discharged
on aspirin, beta-blockers, and statins respectively. Furthermore, 61% of
patients with diabetes and 82% of patients with documented fasting total
cholesterol of ≥5.5 mmol/L were prescribed statins.
With respect to ACE-inhibitor or angiotension-II-antagonist,
55% of ACS patients, 79% of patients with a history of heart failure, and 80% of
patients with anterior STEMI were prescribed either of the medications on
discharge. These medications were used in 82% of patients with ≥ moderate
and 73% in patients with ≥ mild left ventricular impairment.
Use of heparin in NSTEMI /
unstable angina—Of the 382 patients with NSTEMI or unstable angina,
93% were commenced on IV heparin or low molecular weight heparin in the first 24
hours during the admission.
Use of clopidogrel and
glycoprotein IIbIIIa inhibitors in NSTEMI—Of the 239 patients with
NSTEMI, 59% received clopidogrel and 37% received glycoprotein IIbIIIa
inhibitors. For the 65 patients who only had medical treatment without
angiography, 4(6.1%) had clopidogrel and 4(6.1%) had glycoprotein IIbIIIa
inhibitors. The remaining 174 patients (representing 73% of NSTEMI patients)
underwent angiography ± revascularisation and amongst them 75% received
clopidogrel and 46% received glycoprotein IIbIIIa inhibitors either prior to or
during the procedure.
Early angiography-directed revascularisation for
NSTEMI—For these 174 patients, 89 had angiography-directed medical
management, 91 had percutaneous coronary intervention (PCI), and 49 had
inpatient coronary bypass graft for revascularisation. Thus, of all 239 patients
with NSTEMI, PCI was performed in 38% and coronary bypass graft in 21%.
Management of
STEMI—For the 195 patients with STEMI, 75% received thrombolysis.
For the remaining 25% not having thrombolysis, the reasons included late
presentations (9.7%), clear contraindication(s) for thrombolysis (6.7%),
inappropriate clinical decisions (4.6%), and primary angioplasty (4.0%).
For patients who were thrombolysed, 46% received
streptokinase and 54% reteplases. The mean door-to-needle time from arrival into
the Emergency Department to thrombolysis was 49 minutes.
When thrombolysis was conducted in Coronary Care from August
2000 to May 2002 (N=101), the time was 62 minutes but this shortened to 38
minutes since thrombolysis was initiated in the Accident and Emergency
Department of Dunedin Hospital in July 2002.
Amongst the 195 patients with STEMI, 67% (n=131) had
inpatient coronary angiography, 51% (n=99) had inpatient PCI, including 8
patients with primary PCI and 14 patients with rescue PCI after failed
thrombolysis which was defined as persistent pain with ST elevation 120 minutes
post-thrombolysis.
Of the 99 who had PCI, the majority (n=77) had deferred PCI
which was mostly preformed 24 hours later. Thirteen patients (7%) received
inpatient coronary artery bypass graft. Overall, 91% of STEMI admissions
received reperfusion and/or revascularisation therapy.
Comparison with other
registry data—The management of patients with ACS in Dunedin was
compared with EUROASPIRE II5 1999–2000 (N=8181), GRACE6 1999–2000
(N=12,666), CRUSADE7 2002 (N=19,000), and the NZACS Audit8 2002 (N=721).
Compared with the CRUSADE registry, there was more frequent use of less
expensive medications (aspirin, beta-blockers, and heparin) and a less frequent
use of the more expensive glycoprotein IIbIIIa inhibitors and clopidogrel in
Dunedin (Table 3).
Table 1. Patient demographics (N=577)
Table 2. Use of medications amongst patients admitted
with ACS 2001–2002
Table 3. Medications used in the first 24 hours during
the index admission
*19,000 ACS patients treated at 300 US hospitals during
2002; †577 ACS patients admitted into Dunedin CCU in 2001–2002
Table 4 reported the comparisons with EUROASPIRE II, GRACE,
CRUSADE, and the NZACS Audit. At discharge, the use of aspirin in Dunedin was
the highest amongst the five registries (p<0.0005). The use of beta-blockers
in Dunedin was equal to CRUSADE but higher than the other registries
(p<0.0005); while the use of aspirin, statins, and beta-blockers exceeded
NZACS (p<0.05).
Table 4. Comparison of discharge medications
α 577 ACS patients
admitted into Dunedin CCU in
2001-2002
γ 721 ACS patients from all hospitals in New Zealand over 2 weeks in May 2002 Ω 8,181 patients with myocardial infarction admitted into 15 European countries in 1999-2000 δ 6,312 patients from the Global Registry for ACS in 1999-2000 + 19,000 ACS patients treated at 300 US hospitals during 2002 For comparison with NZACSγ, P-value was derived from the highest value of the range: ∗ P<0.05 compared to Dunedin ∗∗ P<0.0005 compared to Dunedin Comparison of the use of
revascularisation for STEMI in Dunedin with registry data—The rate
of revascularisation (coronary angiography, PCI or in-patient CABG) for patients
with STEMI was higher in Dunedin than in the NZACS Audit10 or GRACE11 (Table 5).
Table 5. Comparison of angiography and
revascularisation rates for STEMI
α 577 ACS patients admitted into Dunedin CCU in 2001-2002γ 721 ACS patients from
all hospitals in New Zealand over 2 weeks in May 2002
∗∗ P<0.0005
compared to Dunedin
Management of NSTEMI in
Dunedin, GRACE and NZACS—For patients with NSTEMI, the use of
glycoprotein IIbIIIa inhibitors was 37% in Dunedin, compared to 52% in
GRACE/US,12 27% in GRACE/EUROPE,12 and 20% in GRACE/Australasia-Canada.12
Table 6 shows higher rate of revascularisation (coronary
angiography, PCI or in-patient CABG) for patients with NSTEMI in Dunedin
compared to NZACS10 and GRACE.11 Dunedin’s PCI rate (38%) was comparable
to GRACE/US12 (39%), GRACE/Europe12 (35%) and GRACE/Latin-America12 (34%). The
PCI rate in GRACE/Australasia-Canada12 was 25%.
Table 6 Comparison of angiography and revascularisation
rates for NSTEMI
α 577 ACS patients admitted into Dunedin CCU in 2001-2002γ 721 ACS patients from
all hospitals in New Zealand over 2 weeks in May 2002
∗∗ P<0.0005
compared to Dunedin
DiscussionThis registry study complements the NZACS audit in
documenting the cardiology practice in New Zealand. Our patient population
likely represents a higher risk subgroup than the NZACS Audit8 conducted during
the two-week period in May 2002. NZACS included all patients admitted with a
suspected or definite ACS to any hospital (interventional and
non-interventional) throughout New Zealand. Because Dunedin served as a referral
centre for the whole Otago and Southland District, the current study had a
higher proportion of STEMI (34%) than the NZACS Audit (11%). The NSTEMI rate was
41% for Dunedin and 40% for NZACS. For unstable angina the rate was 25% and 46%
respectively.
Aspirin and
beta-blockers—In Dunedin, the common use of aspirin (98%) exceeded
that of NZACS (80–90%), EUROASPIRE II (90%), GRACE (93%), and the CRUSADE
(88%). Our rate of prescribing beta-blocker (80%) on discharge was comparable to
local and internationally published registries.
Statins—As of
2001-2002, statins were not fully funded in New Zealand unless the
patient’s condition satisfies the PHARMAC rules. The underuse of statins
has also been discussed in the NZACS Audit8 because clear-cut evidence of
benefit has been shown in the Scandinavian Simvastatin Survival Study13 and the
British Heart Protection Study.14
Before 2002, PHARMAC rule for statins-use was a fasting
cholesterol of ≥ 5.5 mmol/L despite 3 months of diet modification; or a
fasting cholesterol of ≥ 5.0 mmol/L in patients who have undergone
coronary artery bypass grafting.
In ACC/AHA recommendations in 2002 (Appendix 1), the use of
statins was recommended concurrently with diet modification if LDL was
> 2.5 mmol/L, preferably
commenced in hospital to ensure compliance. It is interesting to note that the
use of statins in Dunedin in 2001–2002 (70% on discharge) was higher than
contemporary registries such as EUROASPIRE II (43%), GRACE (47%), and NZACS
(52–62%).
Use of ACE-inhibitor /
angiotensin-II-antagonist—ACE-inhibitor has a Class I indication
(AHA/ACC 1999 and 2002 Guidelines1) for patients who have a history of heart
failure or anterior STEMI and a Class IIa indication in patients with mild
left-ventricular impairment post myocardial infarction, regardless of symptoms
(Appendix 1).
In Dunedin, the medications were used in 79% of heart
failure patients and 84% of patients with anterior STEMI. The HOPE Study15 has
shown the benefit of ramipril in all patients with arterial occlusive disease
and coronary risk factors. Following the publication of CHARM16 and EUROPA,17
ACE-inhibitors may be considered for all patients with coronary artery
disease.18,19 The PEACE Trial20 however, shows that patients with stable
coronary artery disease and normal systolic function treated with intensive
medical therapy and appropriately revascularised would not benefit from ACE
inhibitor.
From Table 4 reporting the use of discharge medications, it
is worth noting that the EUROASPIRE II and GRACE registries contained only
patients with STEMI and NSTEMI, and they had higher risk than patients with
unstable angina who were also included in both the current study and the NZACS
audit.8 While concerns has been raised that the use of EBM for ACS in New
Zealand in general could be suboptimal,8 we found the use of EBM in Dunedin
Coronary Care comparable to international practice.
Use of revascularisation
for NSTEMI—The optimal treatment for unstable angina/non-STEMI was
controversial in 2001-2002. Earlier studies like TIMI IIIb21 and VANQWISH22
failed to show significant benefit in an early invasive strategy in reducing
cardiovascular morbidity and mortality. These earlier studies predated the use
of stents and glycoprotein inhibitors. They included relatively small numbers of
patients and there was only a small difference in revascularisation rate between
the conservative and invasive arms of the studies.
More recent studies such as FRISC II23 (2000), TACTICS
TIMI-1824 (2001) and RITA-III25 (2002) all showed definite benefit from
revascularisation in reducing recurrent ischaemia, re-infarction and
re-hospitalisation. These three landmark trials were incorporated in the 2002
ACC/AHA Guidelines for NSTEMI / unstable angina2 recommending routine use of
early invasive revascularisation for higher risk patients. In Dunedin, a
selective invasive strategy for patients with NSTEMI was used, as reflected by a
high rate of inpatient routine coronary angiography (73%), PCI (38%) and
coronary artery bypass graft (21%).
This rate of PCI (38%) for NSTEMI was comparable to
GRACE/USA12 at 40%, GRACE/Europe12 (35%), GRACE/Latin-America12 (34%) and higher
than the GRACE/Australasia-Canada rate (25%). Of note, the rate of PCI in NZACS
was 8%.
Clopidogrel and
glycoprotein IIbIIIa inhibitors—The indication for clopidogrel has
changed in the last 5 years. The 2002 ACC/AHA Guidelines2 for clopidogrel became
Class I for NSTEMI / unstable angina following the CURE26 study, which showed a
2.2% absolute reduction in the composite end-point of cardiovascular death,
myocardial infarction or stroke in patients with unstable angina / NSTEMI over 9
months, with a 1% absolute excess risk of major bleeding.
The upstream use of glycoprotein IIbIIIa inhibitors,
concurrently with aspirin and heparin, is now universally recommended for
non-STEMI / unstable angina on admission if PCI is planned. In Dunedin the use
of clopidogrel (59%) and glycoprotein IIbIIIa inhibitors (37%) in NSTEMI was
consistent with the higher use of angiography and interventions.
Primary PCI and
revascularisation for STEMI—The ACC/AHA Guidelines for PTCA in
STEMI have not changed between 1999 and 2002. Only 4% of STEMI presented to our
Coronary Care received primary PCI, which had a Class I indication. Dunedin
Hospital does not provide a 24-hour primary PCI service. Routine deferred PCI
post-thrombolysis was not recommended in the 2002 ACC/AHA Guidelines.2
Our use of deferred PCI in 40% (n=77) of STEMI patients
might represent a more pharmacoinvasive approach than was recommended.
GRACIA-1,27 published in 2004, showed routine early catheterisation post
thrombolysis (<24 hours) for STEMI is safe (without any increase of major
bleeding and vascular complications) and also beneficial. There was less
revascularisation for symptomatic ischaemia after discharge up to one year in
the invasive group compared to the conservative group (4%
vs 12%,
p=0.001), although the
difference in the rate of death or
reinfarction was not statistically significant (7% vs 12%,
p=0.07).
Clinical
implications—The use of EBM was variable in New Zealand hospitals
as reflected by the different results between the current study and the NZACS
audit. However, both studies revealed room for improvement in treating ACS. The
MINAP28 audit database from the UK demonstrates how an ongoing national
electronic audit system with feedback to clinicians could increase the
prescribing rate of proven secondary therapy in ACS. By 2002–2003, after 3
years of implementation, the MINAP registry has a discharge rate of aspirin at
90%, beta-blocker 83%, ACE-inhibitor 72%, and statins 84%. These figures are
quite impressive and a similar database may be set up in New Zealand to provide
clinicians with treatment audits and continuous feedback to increase the
prescribing of EBM.
Evidence is mounting in daily practice outside the context
of clinical trials supporting the use of EBM in reducing mortality in patients
with ACS. Mukherjee29 showed a progressive and independent survival benefit with
incremental reduction in 6-month mortality when aspirin, beta-blocker, statins
and ACE-inhibitor were increasingly prescribed. One year follow up data by
Schiele30 demonstrated superior survival rate in patients who adhered more to
EBM and revascularisation therapy following myocardial infarction, regardless of
their baseline risk.
Whether the adherence to EBM and the use of more aggressive
revascularisation strategy for STEMI and NSTEMI translate into better long-term
outcomes in New Zealand will be the subject of future studies.
Author information:
Eng Wei Tang, Senior Research Fellow; Cheuk-Kit Wong, Associate Professor in
Medicine; Gerard Wilkins, Associate Professor in Medicine; Peter Herbison,
Statistician and Associate Professor; Michael Williams, Consultant Cardiologist;
Patrick Kay, Consultant Cardiologist; Norma Restieaux, Consultant Cardiologist;
Department of Cardiology, Dunedin School of Medicine, University of Otago (and
Dunedin Public Hospital), Dunedin
Acknowledgements: Dr
EW Tang received support from The Cardiac Society of Australia and New Zealand /
MSD Fellowship as well as partial support from the University of Otago Frances G
Cotter Scholarship. Sue Kelly (Clinical Charge Nurse) prospectively recorded all
door-to-needle times for patients with STEMI who received thrombolysis.
Correspondence: Dr
Cheuk-Kit Wong, Associate Professor in Medicine, Department of Cardiology,
Dunedin School of Medicine, University of Otago, Private Bag , Dunedin. Fax:
(03) 474 7655; email: cheuk-kit.wong@healthotago.co.nz
References:
Appendix 1
AHA/ACC Guidelines for medical treatment of ACS1,2
Aspirin Early Early
B-blocker <12
hour <12 hour
Statins NCEP—
ATP IIIΔ
Class
I: Class
I:
Dietary
modification for 3 months Fibrate or niacin if HDL < 1.0mmol/L
If
LDL still > 3.2mmol/L,
Class
IIa:
start
drug to keep LDL < 2.5 mmol/L Statins and diet if LDL > 2.5mmol/L
and
If
HDL < 0.9mmol/L, start
exercise. commence
24-96 hours after admission
ACE-I/AIIA Class
I
(CCF
or <24 hours post
Class
I
(CCF
or <24 hours post
anterior
STEMI) anterior
STEMI)
Class
IIa (mild LV impairment post
MI; Class IIa
(mild LV impairment post MI;
Asymptomatic) Asymptomatic)
ΔExpert Panel on
Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
Executive Summary of The Third Report of The National Cholesterol Education
Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High
Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA.
2001;285:2486-97.
Class
I: Evidence and/or general agreement that
a given diagnostic procedure/treatment is beneficial, useful and
effective
Class IIa: Weight of
evidence/opinion is in favour of usefulness/efficacy
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