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Department of Cardiothoracic Surgery, North Shore University Medical Center, 300 Community Dr, Manhasset, NY 11030
(Email: resposit{at}nshs.edu).
In the current era of widespread clopidogrel treatment for acute coronary syndromes and percutaneous coronary interventions, the most intriguing question raised by the study of Gao and colleagues [1] is the effect of clopidogrel on coronary artery bypass graft (CABG) patency. A key finding of this report is the excellent 1-year patency of saphenous vein grafts using clopidogrel treatment only (93.5%) or combined with aspirin (96.3%). This observation represents a significant improvement in vein graft patency over that which has been traditionally reported. Parenthetically, almost identical results on graft patency have been reported in other contemporary studies using aspirin alone as the primary antiplatelet medication [2].
Because of the similarity in graft patency rates using different antiplatelet drugs, it is difficult to determine if clopidogrel represents an advance in antiplatelet therapy. The omission of an aspirin-only group in the Gao study resulted in a lost opportunity for a direct head to head comparison between clopidogrel and aspirin. However, the possibility still remains of a beneficial effect of combination therapy of aspirin and clopidogrel, as evidenced by a trend towards improved 1-year patency when both agents were used.
The benefit of clopidogrel on the outcome of CABG was evident in two large randomized trials assessing cardiac events in patients with coronary artery disease. In the Clopidogrel vs. Aspirin in Patients at Risk of Ischemic Events Trial (CAPRIE), there was a significant 8.7% relative risk reduction in the primary composite end points of ischemic stroke, myocardial infarction, and vascular death in favor of the clopidogrel-treated patients vs aspirin. A subanalysis of the CAPRIE database demonstrated that in those patients with previous cardiac operations, clopidogrel was associated with a relative risk reduction of 39% for vascular death and 38% for myocardial infarction [3].
The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial (CURE), which randomized 12,562 patients with non-ST segment elevation acute coronary syndrome to receive clopidogrel or placebo in addition to aspirin, showed consistent benefits of clopidogrel across different patient subgroups, including those undergoing revascularization procedures. Specifically, the combination of clopidogrel and aspirin resulted in a 19% reduction relative to aspirin alone in the occurrence of cardiovascular death, myocardial infarction, or stroke among those patients who underwent CABG during the initial hospitalization [4]. Although clopidogrel treatment clearly reduced adverse outcomes in these two studies, it is not clear if this benefit was the result of an improvement in coronary graft patency.
The answer to the question of the effect of clopidogrel on coronary artery graft patency may be forthcoming. The Clopidogrel After Surgery for Coronary Artery Disease Trial (CASCADE), a randomized double blind study comparing the combination of clopidogrel and aspirin vs aspirin alone on angiographic vein graft patency at 1 year is currently underway and scheduled for completion in November 2009. The data from this trial may provide the scientific rationale for the addition of clopidogrel to the standard antiplatelet regimen of aspirin after CABG operations [5].
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