There is no evidence that the benefit of clopidogrel over aspirin is amplified in patients with a history of ischemic events.

Abstract

HomeStrokeVol. 35, No. 10There Is No Evidence That the Benefit of Clopidogrel Over Aspirin Is Amplified in Patients With a History of Ischemic Events Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBThere Is No Evidence That the Benefit of Clopidogrel Over Aspirin Is Amplified in Patients With a History of Ischemic Events Stephanie C. Lewis, PhD and Charles P. Warlow, FRCP Stephanie C. LewisStephanie C. Lewis University of Edinburgh, Edinburgh, UK Search for more papers by this author and Charles P. WarlowCharles P. Warlow University of Edinburgh, Edinburgh, UK Search for more papers by this author Originally published12 Aug 2004https://doi.org/10.1161/01.STR.0000141704.28560.d7Stroke. 2004;35:2241Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: August 12, 2004: Previous Version 1 To the Editor:The article by Ringleb et al1 does not prove that the benefit of clopidogrel over aspirin is amplified in patients with a history of ischemic events. The article showed that among a subgroup of patients with preexisting atherosclerotic disease, taken from the CAPRIE trial,2 the relative risk reduction for the outcome of ischemic stroke, myocardial infarction or vascular death for clopidogrel over aspirin was 14.9% (95% CI, 0.3% to 27.3%). This was then compared with the results from the entire CAPRIE population, where the relative risk reduction was 8.7% (95% CI, 0.3% to 16.5%). The CIs for these 2 relative risk reductions overlap greatly, so (ignoring issues around the subgroup not being independent of the whole population) all one can say is that clopidogrel performed somewhat better than aspirin in the whole trial population, and clopidogrel also performed better than aspirin in the subgroup. The apparently increased treatment effect in the high-risk patients could easily have been a chance fluctuation.To prove that the effect of clopidogrel is amplified in high-risk patients, one would need to test whether the treatment effect is different in high-risk patients to low-risk patients, using a formal test for interaction.3 The appropriate data for this calculation were not presented in the article, but from a rough calculation, we think it is unlikely that such a test would be statistically significant.In addition to the problems with the statistical analysis, ‘high-risk’ has been defined by simply using a history of atherosclerotic disease. This is overly simplistic, and a more appropriate approach would be to use a prognostic model to divide patients into high-risk and low-risk groups.It is worrying that an article with such a biased conclusion has been published in the name of the CAPRIE investigators. The authors were, we believe, from contributing clinical centers to the CAPRIE trial, but this article was not approved by the steering committee, as far as we know by the trial statistician.1 Ringleb PA, Bhatt DL, Hirsch AT, Topol EJ, Hacke W, for the CAPRIE investigators. Benefit of clopigogrel over aspirin is amplified in patients with a history of ischemic events. Stroke. 2004; 35: 528–532.LinkGoogle Scholar2 CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996; 348: 1329–1339.CrossrefMedlineGoogle Scholar3 Yusuf S, Wittes J, Probstfield J, Tyroler HA. Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials. JAMA. 1991; 266: 93–98.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By HANKEY G (2005) Is clopidogrel the antiplatelet drug of choice for high-risk patients with stroke/TIA?: No, Journal of Thrombosis and Haemostasis, 10.1111/j.1538-7836.2005.01439.x, 3:6, (1137-1140) October 2004Vol 35, Issue 10 Advertisement Article InformationMetrics https://doi.org/10.1161/01.STR.0000141704.28560.d7PMID: 15308787 Originally publishedAugust 12, 2004 PDF download Advertisement