Author + information
- Deepak L. Bhatt, MD, FACC⁎ (, )
- Marcus D. Flather, MD,
- CHARISMA Executive Committee and CHARISMA Investigators
- ↵⁎Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Desk F25, Cleveland, Ohio 44195
Dr. Gebel takes issue with our recent subgroup analysis of the CHARISMA (Clopidogrel for High Atherothrombotic Risk, Ischemic Stabilization, Management, and Avoidance) study, which he labels improper because he incorrectly believes it was defined by events that occurred after randomization (1,2). In fact, the subgroup consisted of patients with documented ischemic events before randomization and was based upon a liberalized version of the inclusion criteria of the CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trial (3). Of course, any subgroup needs to be interpreted with caution before the results are applied broadly and we went to great lengths in the paper to interpret our findings very conservatively and with the appropriate caveats. The subgroup as defined is one that represents a population in which it is biologically plausible that there might be benefit, and the findings are in keeping with and an extension of several other clopidogrel trials, such as the CLARITY (Clopidogrel as Adjunctive Reperfusion Therapy), COMMIT (Randomized Placebo-Controlled Trial of Adding Clopidogrel to Aspirin in 46,000 Acute Myocardial Infarction Patients), and CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) studies (4–6). Importantly, we conclude by stating that further study is necessary to validate our findings.
Dr. Gebel’s comparisons of our results to the CAPRIE trial, as well as to the MATCH (Management of Atherothrombosis With Clopidogrel in High-Risk Patients) trial, are flawed (7). In the CHARISMA study, the comparison was clopidogrel to placebo, with a background of aspirin therapy. In the CAPRIE trial, the comparison was clopidogrel versus an active control, aspirin, with no placebo arm. The MATCH trial was essentially a comparison of aspirin versus placebo, with a background of clopidogrel. Thus, interpretation of these trials and cross-comparison is not as simple as Dr. Gebel portrays.
He concludes by stating that he does not think the findings would be replicated if the trial were repeated. Indeed, one trial has already been announced that will test the hypothesis of whether adding a novel antithrombotic to aspirin is superior to aspirin alone in patients with prior myocardial infarction, stroke, or peripheral arterial disease. Likely, other trials will also test the value of additional antithrombotic therapy in this patient population, such that we will ultimately have further data to guide decision making about optimal antithrombotic strategies for patients with prior ischemic events.
- American College of Cardiology Foundation