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We agree with Auckland City Hospital (ACH) staff (10 February 2012)1 for the need for caution in the prescribing of dabigatran anticoagulation in patient groups at increased risk of drug-induced bleeding.It is difficult to tell to what extent the authors' concerns about the use of dabigatran seen in patients admitted to the hospital relates to the particular demographics of hospital admissions and to the prescribing of dabigatran in Auckland itself. The population in the ACH preliminary sample was representative of patients admitted to hospital and with complications (both who tend to be older), and not necessarily the whole population using dabigatran.Our analysis of national dispensing (PharmWareHouse) data indicates that during July to December 2011, the same 6 months that the authors observed at ACH, there have been around 11,840 patients prescribed and dispensed dabigatran in New Zealand. This meant 3,500 person-years' exposure to dabigatran (with 23,673 prescriptions). The mean age was 73.0 years and median 75 years, similar to the RE-LY trial's mean of 71.5 years2, and younger than the ACH preliminary series' 76 year mean age and 84 year median.1By domicile, we note there were 785 patients living in the Auckland District Health Board (DHB) catchment dispensed dabigatran, of whom 39% (309) were female, with a mean age of 72.8 years and median age of 75 years (being 3-9 years younger than the Auckland City Hospital preliminary series).However, similar to the ACH series, nationally the proportion of women past/current users dispensed dabigatran was higher than in the RE-LY trial; nationally 60% were male and 40% female, compared with 36% female in RE-LY2 and 42% female in the ACH preliminary series.1 In addition, nationally women dabigatran users were older than men; men's mean age was 71.5 years, median 73; women's mean age was 75.3 years, median 77.In the national dispensing data, of the 11,840 past/current users, 31% of patients (n=3,718) were aged 80 years and over (prevalence 1.3 per 1000 population aged 80+). This proportion was higher than the RE-LY trial's 17% being aged 80+ years.3 Half of all New Zealand's users were aged 75+ (see footnote 1). For those living in the Auckland DHB catchment, 276 users were aged 80+ years (398 aged 75+), being 35% of all ages of users there.Of note, 171 users (1.4% of all users, 4.6% of users aged 80+) were both aged 80 and over and ended up using the 150 mg formulation, with higher proportions for those aged 75+ and for those in Auckland (see footnote 2).The dabigatran datasheet4 and advice to prescribers5,6 in effect have recommended against using the 150mg dose for atrial fibrillation in the very elderly because of the risks of age-related reduced renal clearance-related toxicity. This is where they advise treating patients with atrial fibrillation aged 80+ years with the 110 mg formulation (220mg/day as twice daily 110mg doses), and where the RE-LY trial showed a trend towards increased bleeding with the 150mg dose c.f. warfarin in those aged 75+.7The national dispensing data currently do not provide information on weight nor renal function including creatinine clearance, hence the appropriateness of prescribing cannot be easily assessed on a national level. A great step forward will be when we can readily datamatch pharmaceutical use with laboratory data.We note though varying evidence that some older patients starting on the 150mg dose have then down-titrated to the dose recommended for age. Nationally, 356 patients aged 80+ had been dispensed the 150 mg formulation at any time, hence 52% of patients had apparently reduced to the lower dose 110mg formulation (see footnote 3). Again we cannot tell what proportion of those aged 80+ years remaining on the 150mg dose did so with known adequate renal function, versus what proportion still had compromised renal function at risk of bleeding (needing to reduce their dose as per the blanket guidance for all of that age).Further detail on dabigatran dispensings (including breakdowns by formulation, age/gender and DHB) can be seen in the tables and graphs.We agree with calls for all patients, especially those aged 80 years or older with impaired renal function or low body weight, being carefully evaluated for the risks and benefits of treatment before starting dabigatran,8 and then closely monitoring renal function (footnote 4).4,9 To this end we will continue to publicise these and other risk factors in both primary and secondary care. Scott Metcalfe (scott.metcalfe@pharmac.govt.nz) Chief Advisor Population Medicine Peter Moodie Medical Director PHARMAC, Wellington

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

Scott Metcalfe, Chief Advisor Population Medicine, Peter Moodie, Medical Director, PHARMAC, Wellington

Acknowledgements

Matthew Poynton (Analyst, PHARMAC) extracted PharmWareHouse data. Dr Sue Anne Yee (Therapeutic group manager, PHARMAC) reviewed earlier drafts.

Correspondence

Correspondence Email

scott.metcalfe@pharmac.govt.nz

Competing Interests

Bell S, Nand J, Spriggs D, Young L, Dawes M. Initial experience with dabigatran etexilate at Auckland City Hospital. N Z Med J. 2012 Feb 10;125(1349):105-7. http://journal.nzma.org.nz/journal/125-1349/5064/Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. http://www.nejm.org/doi/full/10.1056/NEJMoa0905561 Erratum in: N Engl J Med. 2010 Nov 4;363(19):1875-6. http://www.nejm.org/doi/full/10.1056/NEJMc1007378 )Boehringer Ingelheim. Dabigatran etexilate. Advisory committee briefing document submitted to the Food and Drug Administration, August 2010.http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/cardiovascularandrenaldrugsadvisorycommittee/ucm226009.pdfTable 7.3.1:8.Boehringer Ingelheim (NZ) Ltd. Dabigatran etexilate (Pradaxa). Medicine data sheet. http://www.medsafe.govt.nz/profs/datasheet/p/pradaxacap.pdfThe use of antithrombotic medicines in general practice: a consensus statement. Best Practice Journal 2011;38:10-27.http://www.bpac.org.nz/magazine/2011/october/antithrombotic.aspThe use of dabigatran in general practice: a cautious approach is recommended. Best Practice Journal 2011;39:10-21.http://www.bpac.org.nz/magazine/2011/september/dabigatran.aspEikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011 May 31;123(21):2363-72. http://circ.ahajournals.org/content/123/21/2363.longHarper P, Young L, Merriman E. Bleeding risk with dabigatran in the frail elderly. N Engl J Med 2012 Mar 1;366:864-6.http://www.nejm.org/doi/full/10.1056/NEJMc1112874Updated data sheet for dabigatran etexilate. Best Practice Journal 2011;41:50-51. http://www.bpac.org.nz/magazine/2011/december/dabigatran.asp

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We agree with Auckland City Hospital (ACH) staff (10 February 2012)1 for the need for caution in the prescribing of dabigatran anticoagulation in patient groups at increased risk of drug-induced bleeding.It is difficult to tell to what extent the authors' concerns about the use of dabigatran seen in patients admitted to the hospital relates to the particular demographics of hospital admissions and to the prescribing of dabigatran in Auckland itself. The population in the ACH preliminary sample was representative of patients admitted to hospital and with complications (both who tend to be older), and not necessarily the whole population using dabigatran.Our analysis of national dispensing (PharmWareHouse) data indicates that during July to December 2011, the same 6 months that the authors observed at ACH, there have been around 11,840 patients prescribed and dispensed dabigatran in New Zealand. This meant 3,500 person-years' exposure to dabigatran (with 23,673 prescriptions). The mean age was 73.0 years and median 75 years, similar to the RE-LY trial's mean of 71.5 years2, and younger than the ACH preliminary series' 76 year mean age and 84 year median.1By domicile, we note there were 785 patients living in the Auckland District Health Board (DHB) catchment dispensed dabigatran, of whom 39% (309) were female, with a mean age of 72.8 years and median age of 75 years (being 3-9 years younger than the Auckland City Hospital preliminary series).However, similar to the ACH series, nationally the proportion of women past/current users dispensed dabigatran was higher than in the RE-LY trial; nationally 60% were male and 40% female, compared with 36% female in RE-LY2 and 42% female in the ACH preliminary series.1 In addition, nationally women dabigatran users were older than men; men's mean age was 71.5 years, median 73; women's mean age was 75.3 years, median 77.In the national dispensing data, of the 11,840 past/current users, 31% of patients (n=3,718) were aged 80 years and over (prevalence 1.3 per 1000 population aged 80+). This proportion was higher than the RE-LY trial's 17% being aged 80+ years.3 Half of all New Zealand's users were aged 75+ (see footnote 1). For those living in the Auckland DHB catchment, 276 users were aged 80+ years (398 aged 75+), being 35% of all ages of users there.Of note, 171 users (1.4% of all users, 4.6% of users aged 80+) were both aged 80 and over and ended up using the 150 mg formulation, with higher proportions for those aged 75+ and for those in Auckland (see footnote 2).The dabigatran datasheet4 and advice to prescribers5,6 in effect have recommended against using the 150mg dose for atrial fibrillation in the very elderly because of the risks of age-related reduced renal clearance-related toxicity. This is where they advise treating patients with atrial fibrillation aged 80+ years with the 110 mg formulation (220mg/day as twice daily 110mg doses), and where the RE-LY trial showed a trend towards increased bleeding with the 150mg dose c.f. warfarin in those aged 75+.7The national dispensing data currently do not provide information on weight nor renal function including creatinine clearance, hence the appropriateness of prescribing cannot be easily assessed on a national level. A great step forward will be when we can readily datamatch pharmaceutical use with laboratory data.We note though varying evidence that some older patients starting on the 150mg dose have then down-titrated to the dose recommended for age. Nationally, 356 patients aged 80+ had been dispensed the 150 mg formulation at any time, hence 52% of patients had apparently reduced to the lower dose 110mg formulation (see footnote 3). Again we cannot tell what proportion of those aged 80+ years remaining on the 150mg dose did so with known adequate renal function, versus what proportion still had compromised renal function at risk of bleeding (needing to reduce their dose as per the blanket guidance for all of that age).Further detail on dabigatran dispensings (including breakdowns by formulation, age/gender and DHB) can be seen in the tables and graphs.We agree with calls for all patients, especially those aged 80 years or older with impaired renal function or low body weight, being carefully evaluated for the risks and benefits of treatment before starting dabigatran,8 and then closely monitoring renal function (footnote 4).4,9 To this end we will continue to publicise these and other risk factors in both primary and secondary care. Scott Metcalfe (scott.metcalfe@pharmac.govt.nz) Chief Advisor Population Medicine Peter Moodie Medical Director PHARMAC, Wellington

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

Scott Metcalfe, Chief Advisor Population Medicine, Peter Moodie, Medical Director, PHARMAC, Wellington

Acknowledgements

Matthew Poynton (Analyst, PHARMAC) extracted PharmWareHouse data. Dr Sue Anne Yee (Therapeutic group manager, PHARMAC) reviewed earlier drafts.

Correspondence

Correspondence Email

scott.metcalfe@pharmac.govt.nz

Competing Interests

Bell S, Nand J, Spriggs D, Young L, Dawes M. Initial experience with dabigatran etexilate at Auckland City Hospital. N Z Med J. 2012 Feb 10;125(1349):105-7. http://journal.nzma.org.nz/journal/125-1349/5064/Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. http://www.nejm.org/doi/full/10.1056/NEJMoa0905561 Erratum in: N Engl J Med. 2010 Nov 4;363(19):1875-6. http://www.nejm.org/doi/full/10.1056/NEJMc1007378 )Boehringer Ingelheim. Dabigatran etexilate. Advisory committee briefing document submitted to the Food and Drug Administration, August 2010.http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/cardiovascularandrenaldrugsadvisorycommittee/ucm226009.pdfTable 7.3.1:8.Boehringer Ingelheim (NZ) Ltd. Dabigatran etexilate (Pradaxa). Medicine data sheet. http://www.medsafe.govt.nz/profs/datasheet/p/pradaxacap.pdfThe use of antithrombotic medicines in general practice: a consensus statement. Best Practice Journal 2011;38:10-27.http://www.bpac.org.nz/magazine/2011/october/antithrombotic.aspThe use of dabigatran in general practice: a cautious approach is recommended. Best Practice Journal 2011;39:10-21.http://www.bpac.org.nz/magazine/2011/september/dabigatran.aspEikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011 May 31;123(21):2363-72. http://circ.ahajournals.org/content/123/21/2363.longHarper P, Young L, Merriman E. Bleeding risk with dabigatran in the frail elderly. N Engl J Med 2012 Mar 1;366:864-6.http://www.nejm.org/doi/full/10.1056/NEJMc1112874Updated data sheet for dabigatran etexilate. Best Practice Journal 2011;41:50-51. http://www.bpac.org.nz/magazine/2011/december/dabigatran.asp

Contact diana@nzma.org.nz
for the PDF of this article

View Article PDF

We agree with Auckland City Hospital (ACH) staff (10 February 2012)1 for the need for caution in the prescribing of dabigatran anticoagulation in patient groups at increased risk of drug-induced bleeding.It is difficult to tell to what extent the authors' concerns about the use of dabigatran seen in patients admitted to the hospital relates to the particular demographics of hospital admissions and to the prescribing of dabigatran in Auckland itself. The population in the ACH preliminary sample was representative of patients admitted to hospital and with complications (both who tend to be older), and not necessarily the whole population using dabigatran.Our analysis of national dispensing (PharmWareHouse) data indicates that during July to December 2011, the same 6 months that the authors observed at ACH, there have been around 11,840 patients prescribed and dispensed dabigatran in New Zealand. This meant 3,500 person-years' exposure to dabigatran (with 23,673 prescriptions). The mean age was 73.0 years and median 75 years, similar to the RE-LY trial's mean of 71.5 years2, and younger than the ACH preliminary series' 76 year mean age and 84 year median.1By domicile, we note there were 785 patients living in the Auckland District Health Board (DHB) catchment dispensed dabigatran, of whom 39% (309) were female, with a mean age of 72.8 years and median age of 75 years (being 3-9 years younger than the Auckland City Hospital preliminary series).However, similar to the ACH series, nationally the proportion of women past/current users dispensed dabigatran was higher than in the RE-LY trial; nationally 60% were male and 40% female, compared with 36% female in RE-LY2 and 42% female in the ACH preliminary series.1 In addition, nationally women dabigatran users were older than men; men's mean age was 71.5 years, median 73; women's mean age was 75.3 years, median 77.In the national dispensing data, of the 11,840 past/current users, 31% of patients (n=3,718) were aged 80 years and over (prevalence 1.3 per 1000 population aged 80+). This proportion was higher than the RE-LY trial's 17% being aged 80+ years.3 Half of all New Zealand's users were aged 75+ (see footnote 1). For those living in the Auckland DHB catchment, 276 users were aged 80+ years (398 aged 75+), being 35% of all ages of users there.Of note, 171 users (1.4% of all users, 4.6% of users aged 80+) were both aged 80 and over and ended up using the 150 mg formulation, with higher proportions for those aged 75+ and for those in Auckland (see footnote 2).The dabigatran datasheet4 and advice to prescribers5,6 in effect have recommended against using the 150mg dose for atrial fibrillation in the very elderly because of the risks of age-related reduced renal clearance-related toxicity. This is where they advise treating patients with atrial fibrillation aged 80+ years with the 110 mg formulation (220mg/day as twice daily 110mg doses), and where the RE-LY trial showed a trend towards increased bleeding with the 150mg dose c.f. warfarin in those aged 75+.7The national dispensing data currently do not provide information on weight nor renal function including creatinine clearance, hence the appropriateness of prescribing cannot be easily assessed on a national level. A great step forward will be when we can readily datamatch pharmaceutical use with laboratory data.We note though varying evidence that some older patients starting on the 150mg dose have then down-titrated to the dose recommended for age. Nationally, 356 patients aged 80+ had been dispensed the 150 mg formulation at any time, hence 52% of patients had apparently reduced to the lower dose 110mg formulation (see footnote 3). Again we cannot tell what proportion of those aged 80+ years remaining on the 150mg dose did so with known adequate renal function, versus what proportion still had compromised renal function at risk of bleeding (needing to reduce their dose as per the blanket guidance for all of that age).Further detail on dabigatran dispensings (including breakdowns by formulation, age/gender and DHB) can be seen in the tables and graphs.We agree with calls for all patients, especially those aged 80 years or older with impaired renal function or low body weight, being carefully evaluated for the risks and benefits of treatment before starting dabigatran,8 and then closely monitoring renal function (footnote 4).4,9 To this end we will continue to publicise these and other risk factors in both primary and secondary care. Scott Metcalfe (scott.metcalfe@pharmac.govt.nz) Chief Advisor Population Medicine Peter Moodie Medical Director PHARMAC, Wellington

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

Scott Metcalfe, Chief Advisor Population Medicine, Peter Moodie, Medical Director, PHARMAC, Wellington

Acknowledgements

Matthew Poynton (Analyst, PHARMAC) extracted PharmWareHouse data. Dr Sue Anne Yee (Therapeutic group manager, PHARMAC) reviewed earlier drafts.

Correspondence

Correspondence Email

scott.metcalfe@pharmac.govt.nz

Competing Interests

Bell S, Nand J, Spriggs D, Young L, Dawes M. Initial experience with dabigatran etexilate at Auckland City Hospital. N Z Med J. 2012 Feb 10;125(1349):105-7. http://journal.nzma.org.nz/journal/125-1349/5064/Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. http://www.nejm.org/doi/full/10.1056/NEJMoa0905561 Erratum in: N Engl J Med. 2010 Nov 4;363(19):1875-6. http://www.nejm.org/doi/full/10.1056/NEJMc1007378 )Boehringer Ingelheim. Dabigatran etexilate. Advisory committee briefing document submitted to the Food and Drug Administration, August 2010.http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/cardiovascularandrenaldrugsadvisorycommittee/ucm226009.pdfTable 7.3.1:8.Boehringer Ingelheim (NZ) Ltd. Dabigatran etexilate (Pradaxa). Medicine data sheet. http://www.medsafe.govt.nz/profs/datasheet/p/pradaxacap.pdfThe use of antithrombotic medicines in general practice: a consensus statement. Best Practice Journal 2011;38:10-27.http://www.bpac.org.nz/magazine/2011/october/antithrombotic.aspThe use of dabigatran in general practice: a cautious approach is recommended. Best Practice Journal 2011;39:10-21.http://www.bpac.org.nz/magazine/2011/september/dabigatran.aspEikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011 May 31;123(21):2363-72. http://circ.ahajournals.org/content/123/21/2363.longHarper P, Young L, Merriman E. Bleeding risk with dabigatran in the frail elderly. N Engl J Med 2012 Mar 1;366:864-6.http://www.nejm.org/doi/full/10.1056/NEJMc1112874Updated data sheet for dabigatran etexilate. Best Practice Journal 2011;41:50-51. http://www.bpac.org.nz/magazine/2011/december/dabigatran.asp

Contact diana@nzma.org.nz
for the PDF of this article

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