Showing papers by "Danielle M. Brennan published in 2007"

An analysis of mortality rates with dual-antiplatelet therapy in the primary prevention population of the CHARISMA trial

Abstract: Aims To examine the unanticipated, excess mortality observed in patients randomized to clopidogrel and aspirin vs. aspirin alone in the prespecified ‘asymptomatic’ subgroup of CHARISMA, we investigated whether dual-antiplatelet therapy may be associated with adverse cardiovascular (CV) events in a primary prevention population. Methods and results Of 15 603 patients enrolled, 3284 were initially categorized as asymptomatic with CV risk factors, but 995 had a prior CV event, leaving 2289 patients to represent the primary prevention cohort. This subset was compared with 13 148 symptomatic patients with established vascular disease and both were evaluated for CV death and bleeding. A multivariate analysis analysed predictors of CV death in this group. No post mortem data were available. Compared with aspirin alone, a significant increase in CV death (P ¼ 0.01) was observed in patients receiving dual-antiplatelet therapy in the asymptomatic population. Within the primary prevention cohort, this excess CV death was not significant (P ¼ 0.07). Multivariate analysis of the primary prevention group showed a trend towards excess CV death (P ¼ 0.054; HR 1.72; CI 0.99–2.97) with dual-antiplatelet therapy (aspirin plus clopidogrel). Other independent predictors of CV death included increasing age, hypertension, atrial fibrillation, and a history of heart failure. There was a non-significant increase in moderate or severe bleeding (P ¼ 0.218) with dual-antiplatelet therapy; thus, bleeding was an unlikely explanation for the excess event rate. Conclusion These findings do not support the use of dual-antiplatelet therapy with clopidogrel and aspirin in a primary prevention population. In this subgroup analysis, CV death occurred more frequently than anticipated. The cause of this apparent harm is not elucidated, may represent play of chance, but requires further prospective evaluation.

Prolonged dual antiplatelet therapy after percutaneous coronary intervention reduces ischemic events without affecting the need for repeat revascularization : Insights from the CREDO trial

Abstract: Background. Dual antiplatelet therapy reduces ischemic events after percutaneous coronary intervention (PCI) and in patients with acute coronary syndromes. The relationship between target vessel revascularization (TVR) and ischemic events in patients treated with aspirin and clopidogrel or aspirin alone from 1 month to 1 year after PCI has not been studied. Methods. Patients enrolled in the CREDO trial were treated with aspirin and clopidogrel or aspirin and placebo for up to 1 year. We compared the rates of TVR and ischemic events (cardiac death, myocardial infarction or stroke) in the two groups, and modeled the effect of clopidogrel treatment on ischemic events after adjusting for relevant parameters. Results. One month after PCI, 1,955 patients have remained asymptomatic. By 1 year, ischemic events occurred in 5.3% of placebo- and 3.1% of clopidogrel-treated patients; p = 0.02. The rate of TVR was 11.9% and 12.2%, respectively; p = 0.82. Only 7 patients (clopidogrel: 3 and placebo: 4) experienced TVR within 7 days of an ischemic event. After adjustment, long-term dual antiplatelet therapy was associated with a 48% reduction in events; p = 0.01. Patients who experienced TVR had a significantly higher rate of ischemic events than those without TVR, regardless of treatment assignment: 12.3% vs. 3.1%, respectively; p < 0.001. Conclusion. Thus, after successful PCI, prolonged dual antiplatelet therapy reduces ischemic events without affecting TVR. Overall, patients with TVR experienced an ischemic event much more often that was not related to the PCI vessel. This suggests that the benefit of antiplatelet therapy after coronary revascularization is indexed to the patient's underlying atherothrombotic process, rather than the artery that underwent intervention.