- Email: [email protected]
IIIa inhibitors in acute coronary syndromes
CORRESPONDENCE
resultant effect on reduction of prescribing errors. This would be in line with the recommendations of the UK Government’s 2001 Audit Commission Report,4 which advises integration of the pharmacist within clinical teams to manage medicines more effectively and use of multidisciplinary working to improve the quality of patients’ care. *Nuttan Tanna, Joan Pitkin *Menopause and Osteoporosis, Pharmacy Practice, Research and Development, North West London Hospitals NHS Trust, Harrow, Middlesex HA1 3UJ, UK; and Imperial College School of Science and Medicine, Northwick Park Menopause Clinical and Research Unit, London (e-mail: [email protected]) 1
2
3
4
Dean B, Schachter M, Vincent C, Barber N. Causes of prescribing errors in hospital inpatients: a prospective study. Lancet 2002; 359: 1373–78. Higgins MP, Tully MP. Hospital doctors and ‘appropriate’ prescribing decisions: a schema theory perspective. 8th Health Services Research and Pharmacy Practice Conference, Leeds, April 11–12, 2002: 19 (abstr). Tanna N, Pitkin J, Frank A, Tellez M. Medication management clinics in the secondary care sector. http://www.bmj.com/cgi/eletters/323/7325/1 340#18708 (accessed May 29, 2002). Audit commission report (2001): a spoonful of sugar—medicines management in NHS Hospitals. London: Stationery Office, 2002.
Sir—Bryony Dean and colleagues1 show that safety-oriented prescribing training of doctors is somewhat deficient in the UK; I suspect it is worldwide. The assumption that a pharmacist or a computer will catch the knowledge gaps begs the question that we are afraid of asking: do we dare identify the basic knowledge gaps for fear of sending off whole groups of doctors, such as orthopaedic house staff, for training in prescribing in their typical emergency patients? A result of the introduction of legislation in 2001 that enabled a wider range of health professionals in the UK to prescribe, supply, and administer preparations under patients’ group direction protocols, is that the nonmedical staff involved have to undergo training that is far more rigorous on issues such as dose, indications, and contraindications than that for medical practitioners before similar prescribing. Although the bureaucracy and training time involved are far from welcome, safer prescribers should be produced by this process, compared with those produced from present medical undergraduate curricula and postgraduate apprenticeships. Hopefully studies will be done to investigate this outcome. Extension of prescribing to staff other than doctors cannot be held back
256
just because the medical profession has been unable to reorient its prescribing training from an approach strong in theory but weak in safety detail. The more formalised service-oriented prescribing training that the other professions allied to medicine are already getting, which will be a necessary part of their increasing prescribing rights to come, will force long overdue change. Michael L Jenkinson Department of Health Care of Older People, Queen Elizabeth Queen Mother Hospital, Margate, Kent CT9 4AN, UK (e-mail: [email protected]) 1
Dean B, Schachter M, Vincent C, Barber N. Causes of prescribing errors in hospital inpatients. Lancet 2002; 359: 1373–78.
Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes Sir—Eric Boersma and colleagues (Jan 19, p 189),1 report a meta-analysis of the efficacy and safety of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes who were not routinely scheduled to undergo early coronary revascularisation. We disagree with their assumption that important differences between the trials are unlikely. We also question their conclusion that cardiac endpoints were reduced by glycoprotein IIb/IIIa inhibitors compared with placebo or control in patients not undergoing early revascularisation. Meta-analysis of controlled trials is based on the assumption that each trial provides an unbiased estimate of the effect of an experimental treatment, with variability between studies being attributed to random variation. The trials Boersma and colleagues included varied greatly for drugs used, duration of infusion, enrolment criteria, adjunctive treatment, definition of endpoints, and outcomes. The differences between glycoprotein IIb/IIIa inhibitors used are well documented.2 In TARGET,3 the only study in which two different glycoprotein IIb/IIIa inhibiators were compared directly, agents differed significantly. We believe that the heterogeneity in outcomes between these studies may be due to differences in trial design rather than sampling error. Heterogeneity can be tested for statistically across studies, but a major limitation is that the tests lack power and, therefore, frequently do not reject the null hypothesis of homogenous
results, even if substantial differences exist.4 Boersma and colleagues present a subgroup analysis of the rate of death or myocardial infarction by treatment, according to early use of coronary revascularisation. In patients who underwent early revascularisation, benefit was significant, but in those who did not undergo percutaneous coronary intervention (PCI) within 5 days or PCI or coronary artery bypass grafting within 5 days or 30 days, risk of death or myocardial infarction was not significantly reduced at 30 days. We do not understand how a non-significant trend in a meta-analysis subgroup can justify the conclusion that glycoprotein IIb/IIIa inhibitors in patients not undergoing early revascularisation reduced cardiac endpoints. By contrast, in the CURE study,5 the number of cardiovascular events was significantly reduced at 30 days and consistent benefits were noted irrespective of whether patients underwent revascularisation procedures after randomisation. Yet Boersma and colleagues suggest that patients with acute coronary syndromes received early intense aspirin, heparin, and glycoprotein IIb/IIIa inhibitor therapy, followed by long-term oral thienopyridine. They justify this approach by suggesting that the benefits of glycoprotein IIb/IIIa blockade appear in the first few days, whereas benefits appear gradually during oral treatment with clopidogrel. However, the CURE investigators showed that treatment with clopidogrel significantly lowered the rate of cardiovascular death, myocardial infarction, stroke, or refractory angina as early as 24 h. Given the larger relative risk reduction seen in CURE and lower cost of clopidogrel, we suggest that patients with acute coronary syndromes should be treated with aspirin, heparin, and clopidogrel, and that use of glycoprotein IIb/IIIa inhibitors be restricted to patients undergoing PCI or who have refractory unstable angina. *S A Harding, N A Boon, A D Flapan Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW, UK (e-mail: [email protected]) 1
2
3
Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a metaanalysis of all major randomised clinical trials. Lancet 2002; 359: 189–98. Chew DP, Moliterno DJ. A critical appraisal of platelet glycoprotein IIb/IIIa inhibition. J Am Coll Cardiol 2000; 36: 2028–35. The TARGET investigators. Comparison of two glycoprotein IIb/IIIa platelet
THE LANCET • Vol 360 • July 20, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
CORRESPONDENCE
4
5
inhibitors, tirofiban and abciximab for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med 2001; 344: 1888–94. Egger M, Smith GD, Phillips AN. Metaanalysis: principles and procedures. BMJ 1997; 315: 1533–37. The CURE trial investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without STsegment elevation. N Engl J Med 2001; 345: 494–502.
Sir—Eric Boersma and colleagues’ meta-analysis1 is timely, since antiIIb/IIIa strategies are increasingly being used in acute coronary syndromes, although their benefit still awaits to be assessed. Boersma and colleagues provide evidence of a small risk reduction with glycoprotein IIb/IIIa inhibitors. This finding confirms their hypothesis that, in the designing of each clinical trial, the event reduction by glycoprotein IIb/IIIa treatment had been overestimated. There is, however, another clinical message the investigators largely overlook. Glycoprotein IIb/IIIa inhibitors were associated with an increase in major haemorrhages and the number of caused bleedings was roughly similar to the number of avoided vascular complications. These latter events are more ominous than extracranial major bleedings but still, the benefit ratio of glycoprotein IIb/IIIa agents does not seem to justify their cost. We think Boersma and colleagues’ results are against the routine use of these drugs in patients with acute coronary syndromes not scheduled for revascularisation. The researchers seem to indirectly acknowledge this conclusion and try to identify subgroups of patients best suited for glycoprotein IIb/IIIa blockade. Information gained from subgroup analyses, however, seems to be forced in a rather rigid interpretation framework. The data clearly suggest a sex-related effect with the possibility that glycoprotein IIb/IIIa inhibitors might be harmful to women. However, Boersma and colleagues overemphasise the results of a patients’ stratification made on the basis of largely incomplete troponin value datasets. This stratification does not confirm the sex-related heterogeneity but seems to show a higher benefit in patients with increased troponin values. Accordingly, the investigators advise the use of glycoprotein IIb/IIIa inhibitors in patients with high troponin values while not recommending a differential treatment strategy between men and women. We disagree with this approach since the stratification of patients by troponin values, because of the small
size of the various subgroups, is meaningless and potentially misleading. Furthermore, the hypothesis that highrisk patients might benefit from glycoprotein IIb/IIIa inhibitor treatment had already been tested by in the GUSTO IV ACS study.2 That trial was specifically designed to assess the benefit-to-risk ratio of a glycoprotein IIb/IIIa inhibitor strategy in patients with increased troponin values or persistent ST depression. Researchers in GUSTO IV ACS could show no benefit in high-risk patients— therefore, there is no need to reopen this issue on the grounds of unreliable datasets. On the other hand, Boersma and colleagues should acknowledge that the sex-related heterogeneity, particularly the possibility that glycoprotein IIb/IIIa inhibitor agents may be harmful in women, does deserve adequate scientific attention. This issue, which had already been raised by the PURSUIT trial,3 raises the question as to whether the various thrombotic determinants, mechanisms, or both, may have a different interplay in the two sexes. Finally, we note that some disappointing experiences with oral anti-GpIIb/III agents have already stimulated substantial scientific interest on the possible harmful effects of glycoprotein IIb/IIIa blockade.4 *Raffaele Landolfi, Raimondo De Cristofaro Haemostasis Research Centre, Catholic University School of Medicine, 00168 Rome, Italy 1
2
3
4
Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet 2002; 359: 189–98. The GUSTO IV-ACS Investigators. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. Lancet 2001; 357: 1915–24. The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med 1998; 339: 436–43. Cox D, Smith R, Quinn M, Theroux P, Crean P, Fitzgerald DJ. Evidence of platelet activation during treatment with a GPIIb/IIIa antagonist in patients presenting with acute coronary syndromes. J Am Coll Cardiol 2000; 36: 1514–19.
reduced rate of death or myocardial infarction at 30 days in patients with diabetes. Roffi and colleagues2 have reported a meta-analysis in which they focus on the effect of glycoprotein IIb/IIIa inhibitors on mortality and major cardiac events in patients with diabetes, based on the same databases. By contrast with Boersma and colleagues’ findings, the incidence of death or myocardial infarction at 30 days was significantly reduced in these patients, although they noted a significant degree of divergence between the individual trials. The two meta-analyses had similar inclusion criteria (acute coronary syndromes without ST-segment elevation), statistical analyses (MantelHaenszel method), and endpoint definition (death or myocardial infarction at 30 days). However, the total number of patients is lower in Roffi and colleagues’ study than in that by Boersma and colleagues (29 530 vs 31 402 patients). The number of patients included in the analysis by Roffi and colleagues does not fit the sum of patients that results from addition of those enrolled in each trial. Different selection criteria could explain the discrepancies between the analyses. Such exclusion criteria, however, are not named in the reports. Because of the heterogeneity of results, contradictory conclusions can be drawn from Boersma and colleagues’ and Roffi and colleagues’ meta-analyses. Roffi and colleagues’ data may lead to a preferred application of glycoprotein IIb/IIIa inhibitors in the management of patients with type 2 diabetes and acute coronary syndromes, whereas those of Boersma and colleagues do not convincingly lend support to such a recommendation. We find it astonishing that two meta-analyses of the same databases produce contradicting results. In view of the importance of this subject, efforts should be made to reassess their claims. *Juris J Meier, Baptist Gallwitz, Wolfgang E Schmidt, Michael A Nauck *Department of Medicine I, St Josef Hospital, Ruhr University, D-44791 Bochum, Germany; and Diabeteszentrum, Bad Lauterberg (e-mail: [email protected]) 1
Sir—On the basis of the databases of the studies in their meta-analysis, Eric Boersma and colleagues1 calculate odds ratios in subgroups with various clinical characteristics. To our surprise, they report no significant interaction between the use of glycoprotein IIb/IIIa inhibitors and a
THE LANCET • Vol 360 • July 20, 2002 • www.thelancet.com
2
Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a metaanalysis of all major randomised clinical trials. Lancet 2002; 359: 189–98. Roffi M, Chew DP, Mukherjee D, et al. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndrome. Circulation 2001; 104: 2767–71.
257
For personal use. Only reproduce with permission from The Lancet Publishing Group.
resultant effect on reduction of prescribing errors. This would be in line with the recommendations of the UK Government’s 2001 Audit Commission Report,4 which advises integration of the pharmacist within clinical teams to manage medicines more effectively and use of multidisciplinary working to improve the quality of patients’ care. *Nuttan Tanna, Joan Pitkin *Menopause and Osteoporosis, Pharmacy Practice, Research and Development, North West London Hospitals NHS Trust, Harrow, Middlesex HA1 3UJ, UK; and Imperial College School of Science and Medicine, Northwick Park Menopause Clinical and Research Unit, London (e-mail: [email protected]) 1
2
3
4
Dean B, Schachter M, Vincent C, Barber N. Causes of prescribing errors in hospital inpatients: a prospective study. Lancet 2002; 359: 1373–78. Higgins MP, Tully MP. Hospital doctors and ‘appropriate’ prescribing decisions: a schema theory perspective. 8th Health Services Research and Pharmacy Practice Conference, Leeds, April 11–12, 2002: 19 (abstr). Tanna N, Pitkin J, Frank A, Tellez M. Medication management clinics in the secondary care sector. http://www.bmj.com/cgi/eletters/323/7325/1 340#18708 (accessed May 29, 2002). Audit commission report (2001): a spoonful of sugar—medicines management in NHS Hospitals. London: Stationery Office, 2002.
Sir—Bryony Dean and colleagues1 show that safety-oriented prescribing training of doctors is somewhat deficient in the UK; I suspect it is worldwide. The assumption that a pharmacist or a computer will catch the knowledge gaps begs the question that we are afraid of asking: do we dare identify the basic knowledge gaps for fear of sending off whole groups of doctors, such as orthopaedic house staff, for training in prescribing in their typical emergency patients? A result of the introduction of legislation in 2001 that enabled a wider range of health professionals in the UK to prescribe, supply, and administer preparations under patients’ group direction protocols, is that the nonmedical staff involved have to undergo training that is far more rigorous on issues such as dose, indications, and contraindications than that for medical practitioners before similar prescribing. Although the bureaucracy and training time involved are far from welcome, safer prescribers should be produced by this process, compared with those produced from present medical undergraduate curricula and postgraduate apprenticeships. Hopefully studies will be done to investigate this outcome. Extension of prescribing to staff other than doctors cannot be held back
256
just because the medical profession has been unable to reorient its prescribing training from an approach strong in theory but weak in safety detail. The more formalised service-oriented prescribing training that the other professions allied to medicine are already getting, which will be a necessary part of their increasing prescribing rights to come, will force long overdue change. Michael L Jenkinson Department of Health Care of Older People, Queen Elizabeth Queen Mother Hospital, Margate, Kent CT9 4AN, UK (e-mail: [email protected]) 1
Dean B, Schachter M, Vincent C, Barber N. Causes of prescribing errors in hospital inpatients. Lancet 2002; 359: 1373–78.
Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes Sir—Eric Boersma and colleagues (Jan 19, p 189),1 report a meta-analysis of the efficacy and safety of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes who were not routinely scheduled to undergo early coronary revascularisation. We disagree with their assumption that important differences between the trials are unlikely. We also question their conclusion that cardiac endpoints were reduced by glycoprotein IIb/IIIa inhibitors compared with placebo or control in patients not undergoing early revascularisation. Meta-analysis of controlled trials is based on the assumption that each trial provides an unbiased estimate of the effect of an experimental treatment, with variability between studies being attributed to random variation. The trials Boersma and colleagues included varied greatly for drugs used, duration of infusion, enrolment criteria, adjunctive treatment, definition of endpoints, and outcomes. The differences between glycoprotein IIb/IIIa inhibitors used are well documented.2 In TARGET,3 the only study in which two different glycoprotein IIb/IIIa inhibiators were compared directly, agents differed significantly. We believe that the heterogeneity in outcomes between these studies may be due to differences in trial design rather than sampling error. Heterogeneity can be tested for statistically across studies, but a major limitation is that the tests lack power and, therefore, frequently do not reject the null hypothesis of homogenous
results, even if substantial differences exist.4 Boersma and colleagues present a subgroup analysis of the rate of death or myocardial infarction by treatment, according to early use of coronary revascularisation. In patients who underwent early revascularisation, benefit was significant, but in those who did not undergo percutaneous coronary intervention (PCI) within 5 days or PCI or coronary artery bypass grafting within 5 days or 30 days, risk of death or myocardial infarction was not significantly reduced at 30 days. We do not understand how a non-significant trend in a meta-analysis subgroup can justify the conclusion that glycoprotein IIb/IIIa inhibitors in patients not undergoing early revascularisation reduced cardiac endpoints. By contrast, in the CURE study,5 the number of cardiovascular events was significantly reduced at 30 days and consistent benefits were noted irrespective of whether patients underwent revascularisation procedures after randomisation. Yet Boersma and colleagues suggest that patients with acute coronary syndromes received early intense aspirin, heparin, and glycoprotein IIb/IIIa inhibitor therapy, followed by long-term oral thienopyridine. They justify this approach by suggesting that the benefits of glycoprotein IIb/IIIa blockade appear in the first few days, whereas benefits appear gradually during oral treatment with clopidogrel. However, the CURE investigators showed that treatment with clopidogrel significantly lowered the rate of cardiovascular death, myocardial infarction, stroke, or refractory angina as early as 24 h. Given the larger relative risk reduction seen in CURE and lower cost of clopidogrel, we suggest that patients with acute coronary syndromes should be treated with aspirin, heparin, and clopidogrel, and that use of glycoprotein IIb/IIIa inhibitors be restricted to patients undergoing PCI or who have refractory unstable angina. *S A Harding, N A Boon, A D Flapan Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW, UK (e-mail: [email protected]) 1
2
3
Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a metaanalysis of all major randomised clinical trials. Lancet 2002; 359: 189–98. Chew DP, Moliterno DJ. A critical appraisal of platelet glycoprotein IIb/IIIa inhibition. J Am Coll Cardiol 2000; 36: 2028–35. The TARGET investigators. Comparison of two glycoprotein IIb/IIIa platelet
THE LANCET • Vol 360 • July 20, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
CORRESPONDENCE
4
5
inhibitors, tirofiban and abciximab for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med 2001; 344: 1888–94. Egger M, Smith GD, Phillips AN. Metaanalysis: principles and procedures. BMJ 1997; 315: 1533–37. The CURE trial investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without STsegment elevation. N Engl J Med 2001; 345: 494–502.
Sir—Eric Boersma and colleagues’ meta-analysis1 is timely, since antiIIb/IIIa strategies are increasingly being used in acute coronary syndromes, although their benefit still awaits to be assessed. Boersma and colleagues provide evidence of a small risk reduction with glycoprotein IIb/IIIa inhibitors. This finding confirms their hypothesis that, in the designing of each clinical trial, the event reduction by glycoprotein IIb/IIIa treatment had been overestimated. There is, however, another clinical message the investigators largely overlook. Glycoprotein IIb/IIIa inhibitors were associated with an increase in major haemorrhages and the number of caused bleedings was roughly similar to the number of avoided vascular complications. These latter events are more ominous than extracranial major bleedings but still, the benefit ratio of glycoprotein IIb/IIIa agents does not seem to justify their cost. We think Boersma and colleagues’ results are against the routine use of these drugs in patients with acute coronary syndromes not scheduled for revascularisation. The researchers seem to indirectly acknowledge this conclusion and try to identify subgroups of patients best suited for glycoprotein IIb/IIIa blockade. Information gained from subgroup analyses, however, seems to be forced in a rather rigid interpretation framework. The data clearly suggest a sex-related effect with the possibility that glycoprotein IIb/IIIa inhibitors might be harmful to women. However, Boersma and colleagues overemphasise the results of a patients’ stratification made on the basis of largely incomplete troponin value datasets. This stratification does not confirm the sex-related heterogeneity but seems to show a higher benefit in patients with increased troponin values. Accordingly, the investigators advise the use of glycoprotein IIb/IIIa inhibitors in patients with high troponin values while not recommending a differential treatment strategy between men and women. We disagree with this approach since the stratification of patients by troponin values, because of the small
size of the various subgroups, is meaningless and potentially misleading. Furthermore, the hypothesis that highrisk patients might benefit from glycoprotein IIb/IIIa inhibitor treatment had already been tested by in the GUSTO IV ACS study.2 That trial was specifically designed to assess the benefit-to-risk ratio of a glycoprotein IIb/IIIa inhibitor strategy in patients with increased troponin values or persistent ST depression. Researchers in GUSTO IV ACS could show no benefit in high-risk patients— therefore, there is no need to reopen this issue on the grounds of unreliable datasets. On the other hand, Boersma and colleagues should acknowledge that the sex-related heterogeneity, particularly the possibility that glycoprotein IIb/IIIa inhibitor agents may be harmful in women, does deserve adequate scientific attention. This issue, which had already been raised by the PURSUIT trial,3 raises the question as to whether the various thrombotic determinants, mechanisms, or both, may have a different interplay in the two sexes. Finally, we note that some disappointing experiences with oral anti-GpIIb/III agents have already stimulated substantial scientific interest on the possible harmful effects of glycoprotein IIb/IIIa blockade.4 *Raffaele Landolfi, Raimondo De Cristofaro Haemostasis Research Centre, Catholic University School of Medicine, 00168 Rome, Italy 1
2
3
4
Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet 2002; 359: 189–98. The GUSTO IV-ACS Investigators. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. Lancet 2001; 357: 1915–24. The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med 1998; 339: 436–43. Cox D, Smith R, Quinn M, Theroux P, Crean P, Fitzgerald DJ. Evidence of platelet activation during treatment with a GPIIb/IIIa antagonist in patients presenting with acute coronary syndromes. J Am Coll Cardiol 2000; 36: 1514–19.
reduced rate of death or myocardial infarction at 30 days in patients with diabetes. Roffi and colleagues2 have reported a meta-analysis in which they focus on the effect of glycoprotein IIb/IIIa inhibitors on mortality and major cardiac events in patients with diabetes, based on the same databases. By contrast with Boersma and colleagues’ findings, the incidence of death or myocardial infarction at 30 days was significantly reduced in these patients, although they noted a significant degree of divergence between the individual trials. The two meta-analyses had similar inclusion criteria (acute coronary syndromes without ST-segment elevation), statistical analyses (MantelHaenszel method), and endpoint definition (death or myocardial infarction at 30 days). However, the total number of patients is lower in Roffi and colleagues’ study than in that by Boersma and colleagues (29 530 vs 31 402 patients). The number of patients included in the analysis by Roffi and colleagues does not fit the sum of patients that results from addition of those enrolled in each trial. Different selection criteria could explain the discrepancies between the analyses. Such exclusion criteria, however, are not named in the reports. Because of the heterogeneity of results, contradictory conclusions can be drawn from Boersma and colleagues’ and Roffi and colleagues’ meta-analyses. Roffi and colleagues’ data may lead to a preferred application of glycoprotein IIb/IIIa inhibitors in the management of patients with type 2 diabetes and acute coronary syndromes, whereas those of Boersma and colleagues do not convincingly lend support to such a recommendation. We find it astonishing that two meta-analyses of the same databases produce contradicting results. In view of the importance of this subject, efforts should be made to reassess their claims. *Juris J Meier, Baptist Gallwitz, Wolfgang E Schmidt, Michael A Nauck *Department of Medicine I, St Josef Hospital, Ruhr University, D-44791 Bochum, Germany; and Diabeteszentrum, Bad Lauterberg (e-mail: [email protected]) 1
Sir—On the basis of the databases of the studies in their meta-analysis, Eric Boersma and colleagues1 calculate odds ratios in subgroups with various clinical characteristics. To our surprise, they report no significant interaction between the use of glycoprotein IIb/IIIa inhibitors and a
THE LANCET • Vol 360 • July 20, 2002 • www.thelancet.com
2
Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a metaanalysis of all major randomised clinical trials. Lancet 2002; 359: 189–98. Roffi M, Chew DP, Mukherjee D, et al. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndrome. Circulation 2001; 104: 2767–71.
257
For personal use. Only reproduce with permission from The Lancet Publishing Group.