European Heart Journal Advance Access originally published online on July 25, 2005
European Heart Journal 2005 26(18):1933; doi:10.1093/eurheartj/ehi435
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Combined pharmacological treatment with clopidogrel and statin for patients with acute coronary syndrome: is there a survival advantage?: reply
Division of Cardiology
School of Medicine
Saint Louis University
Saint Louis
MO
USA
Duke Clinical Research Institute
Durham
NC
USA
Tel: +919 668 8971
Fax: +919 668 7056
E-mail address: mehta007{at}dcri.duke.edu
We thank Dr Almsherqui and his colleagues for their comments concerning our recently published study.1 Our goal was to evaluate whether there was any clinically relevant drug interactions between clopidogrel and statins that would have otherwise attenuated the independent beneficial effects of these drugs when given to patients with acute coronary syndromes. In accordance with the retrospective and observational nature of our study, we used currently accepted methodology that included adjustments using Cox proportional hazard model and propensity analysis to not only account for differences in baseline confounders and in-hospital medications, procedures, and revascularization but also for the propensity for being in the group receiving aspirin+clopidogrel+statin vs. aspirin+clopidogrel (group IV vs. group II). Despite these rigorous adjustments, the 6-month mortality in group IV was significantly lower than that in group II. Thus, within the known constraints of an observational analysis addressing similar issues, we believe that our conclusion that there is a lack of significant attenuation of the independent effects of the two drugs by their use in combination remains appropriate.
Three other observational studies have shown similar results.2–4 In our study, the group that received the combination of aspirin, clopidogrel, and statin had lower mortality than the other three groups, supporting the possibility that perhaps there may be synergism when these drugs are used in combination rather than independently. We do not dispute with Dr Almsherqui and his colleagues that to definitively address the clinical dilemma of the lack of clinically relevant drug interaction and potential synergistic effect between clopidogrel and statin, a rigorous randomized study will be necessary. The data from our study and other similar investigations should just be regarded as hypothesis-generating and form the foundation for future prospective randomized trial addressing this issue.
References
- Lim MJ, Spencer FA, Gore JM, Dabbous OH, Agnelli G, Kline-Rogers EM, DiBeneditto D, Eagle KA, Mehta RH. for the GRACE Investigators. Impact of combined pharmacologic treatment with clopidogrel and a statin on outcomes of patients with non-ST-segment elevation acute coronary syndromes: perspectives from a large multinational registry. Eur Heart J 2005;26:1063–1069.
[Abstract/Free Full Text] - Saw J, Steinhubl SR, Berger PB, Kereiakes DJ, Serebruany VL, Brennan D, Topol EJ. Lack of adverse clopidogrel-atorvastatin clinical interaction from secondary analysis of a randomized placebo-controlled clopidogrel trial. Circulation 2003;108:921–924.
[Abstract/Free Full Text] - Weinbergen H, Gitt A, Shiele R, Juenger C, Heer T, Meisenzahl C, Limbourg P, Bossaller C, Senges J. Comparison of clinical benefits of clopidogrel therapy in patients with acute coronary syndromes taking atorvastatin versus other statin therapies. Am J Cardiol 2003;92:285–288.[CrossRef][Web of Science][Medline]
- Mukherjee D, Kline-Rodgers E, Fang J, Munir K, Eagle KA. Lack of clopidogrel-CYP3A4 statin interaction in patients with acute coronary syndrome. Heart 2005;91:23–26.
[Abstract/Free Full Text]
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