Charisma Trial - Clopidogrel

Extractos da Secção de Correspondência do NEJM de 27 de Julho de 2006

"To the Editor: The CHARISMA trial suffers from a basic methodologic limitation, also present in prior large trials of clopidogrel: the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial1 and the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study.2 In a study designed to compare the effectiveness (in terms of the prevention of thrombotic events) of one antiplatelet therapy (aspirin) with that of a second therapy (clopidogrel with or without aspirin), the results are obviously biased toward the second therapy if patients who had a thrombotic event while taking aspirin (owing to the failure of aspirin therapy) are included. From methodologic and clinical standpoints, patients with and those without a history of unsuccessful aspirin therapy can be included in the study but should be separated at randomization and in analyses."

"The author replies: The combination of clopidogrel and aspirin was indeed associated with an increased incidence of bleeding complications, as compared with aspirin alone, as noted by Kongsaengdao and Arayawichanont. Their Table 1 is correct except for the double-counting of the severe and moderate bleeding complications that occurred in some patients. Fatal and intracerebral hemorrhage were tallied in the severe bleeding category. The correct point estimate for severe and moderate bleeding among patients receiving aspirin and placebo is 2.5 percent, and that for the composite of fatal bleeding, intracerebral hemorrhage, and moderate bleeding is 2.6 percent among patients receiving clopidogrel and aspirin."

"To the Editor: In the April 20 issue Bhatt et al. reported the results of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study.1 As a vascular neurologist, I want to highlight a specific piece of information that may be missed in the wealth of data provided in the article.
Table 4 indicates that there was a marginal reduction in the risk of nonfatal stroke among patients receiving the dual antiplatelet therapy, as compared with patients receiving placebo plus aspirin, despite the fact that there were similar rates of nonfatal ischemic stroke in the two groups. Since there was no difference in the overall occurrence of primary intracranial hemorrhage, these numbers can be explained only by an excess of fatal intracerebral hemorrhages in the group receiving clopidogrel plus aspirin (nine patients, as compared with two patients in the group receiving placebo plus aspirin, according to my calculations).
Even though the incidence of fatal intracerebral hemorrhage in the total population was very low, the difference in the distribution of this complication between the two groups deserves to be noted."