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• Potential Statin-Clopidogrel Interaction Requires Randomised, Prospective Study
  Horst Neubauer
  Published on: 23 February 2005

• Published on: 23 February 2005

  Potential Statin-Clopidogrel Interaction Requires Randomised, Prospective Study

  • Horst Neubauer, Dr.
  • Other Contributors:
    • Andreas Mügge, Prof. Dr.

  Dear Editor,

  The study of Mukherjee and co-workers [1] on the problem of statin and clopidogrel interaction is certainly of clinical interest. The study is similar to the re-evaluation of the CREDO-data [2] and the MITRAplus- data [3] but there are some limitations to consider: The study is retrospective and not randomised, and the subgroups differ substantially in many aspects. The major criticism is that the au...

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  Dear Editor,

  The study of Mukherjee and co-workers [1] on the problem of statin and clopidogrel interaction is certainly of clinical interest. The study is similar to the re-evaluation of the CREDO-data [2] and the MITRAplus- data [3] but there are some limitations to consider: The study is retrospective and not randomised, and the subgroups differ substantially in many aspects. The major criticism is that the authors do not describe the initial therapeutic procedure of acute coronary syndrome (ACS) in their patients (primary percutaneous coronary intervention (PCI) with/without stenting, thrombolysis, coronary artery bypass grafting (CABG)) as these factors may have more impact on the clinical outcome than the combined use of statins and clopidogrel. The clopidogrel-statin drug-drug interaction may be of particular interest in patients undergoing stenting because of the risk of stent thrombosis in the case of a diminished clopidogrel effect. Therefore adequate endpoints could be stent thrombosis, myocardial infarction or revascularization of the target vessel. None of these conditions were analyzed by the authors. Instead they used overall death, myocardial infarction (irrespectively of the target vessel), and stroke (which appears not relevant regarding the working hypothesis). These composite endpoints may not be sufficient to analyse a possible adverse effect because of clopidogrel-statin interaction. Furthermore other important details were ignored in the paper: The data on the dosage of statins and the number of different statins used are lacking and it is not apparent how long the patients were given statin medication. In the discussion Mukherjee et al. emphasized that the presented data are in line with the report by Muller [4] et al. (600mg clopidogrel loading dosage), but it is not clear when and how the clopidogrel therapy was initiated (300mg loading or no loading) and how long it was sustained in their study group.

  On the whole, the study presented by Mukherjee et al. retrospectively assesses statin co-medication on patients treated with clopidogrel without contributing very much to the on-going discussion on the clinical relevance of this clopidogrel-statin drug-drug interaction as they disregard other important factors on the clinical outcome of patients with ACS. Therefore randomized, prospective trials are an absolute must!

  Dr. Horst Neubauer, Prof. Dr. Andreas Mügge,
  Clinic of Cardiology & Angiology, BG Kliniken Bergmannsheil/St. Josef-Hospital, University Hospitals, Ruhr-University Gudrunstrasse 56, 44791 Bochum, Germany E-Mail: Horst.Neubauer@rub.de

  References:

  [1] Mukherjee D, Kline-Rogers E, Fang J et al. Lack of clopidogrel-CYP3A4 statin interaction in patients with acute coronary syndrome. Heart 2005;91:23-6.

  [2] Saw J, Steinhubl SR, Berger PB et al. Lack of adverse clopidogrel- atorvastatin clinical interaction from secondary analysis of a randomized, placebo-controlled clopidogrel trial. Circulation 2003;108:921-4.

  [3] Wienbergen H, Gitt AK, Schiele R et al. Comparison of clinical benefits of clopidogrel therapy in patients with acute coronary syndromes taking atorvastatin versus other statin therapies. Am J Cardiol 2003;92:285-8.

  [4] Muller I, Besta F, Schulz C et al. Effects of statins on platelet inhibition by a high loading dose of clopidogrel. Circulation 2003;108:2195-7.

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  Conflict of Interest:
  None declared.

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