Heart Care Info - Heart Disease Prevention & Treatment

Clopidogrel After Coronary Artery Bypass Graft Surgery: Insufficient Evidence

A Kulik... - Journal of the American College of ..., 2011 - Am Coll Cardio Found We recently read the interesting study by Srensen et al.(1), which evaluated the efficacy of clopidogrel after coronary artery bypass graft surgery (CABG) following a recent myocardial infarction (MI). Using data from 3,545 patients, the authors reported a lower risk of death ...

Alexander Kulik, MD, MPH* and Marc Ruel, MD, MPH

We recently read the interesting study by S rensen et al. (1), which evaluated the efficacy of clopidogrel after coronary artery bypass graft surgery (CABG) following a recent myocardial infarction (MI). Using data from 3,545 patients, the authors reported a lower risk of death and the combined endpoint of death or recurrent MI in patients who received clopidogrel after surgery. Based on their results, the authors recommend that a "focus on discharge clopidogrel treatment of these patients should be made" (1).

Because their study was nonrandomized, the authors used multivariate and propensity-score analyses to control for possible confounders. Interestingly though, no adjustment was made for the use of on- or off-pump CABG. In theory, any benefit associated with clopidogrel after CABG would be seen in an improvement in graft patency and the prevention of myocardial events. However, clopidogrel did not significantly reduce the incidence of recurrent MI, cardiovascular death, or the need for repeat revascularization in this study. How could clopidogrel lower the risk of death and yet not reduce the incidence of myocardial events after CABG? Although no explanation was provided by the authors, perhaps this finding relates to residual confounding. Clopidogrel may have been administered preferentially to healthier patients in this cohort who were believed to have a better chance for long-term survival.

S rensen et al. (1) imply in their paper that clopidogrel is underused after CABG, referring to the current guidelines that recommend postoperative clopidogrel treatment for 9 to 12 months for patients who undergo CABG following MI (2). This recommendation was based primarily on data from the Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE) trial that reported significantly fewer adverse cardiac events among MI patients treated with the combination of clopidogrel and aspirin compared with aspirin alone, even if they ultimately underwent CABG (3). However, subgroup analysis later revealed that the benefit of combined antiplatelet therapy was entirely preoperative while patients were awaiting surgery. No benefit was seen for clopidogrel use after CABG in the CURE trial (4). Therefore, it is not surprising that many surgeons do not routinely prescribe clopidogrel after CABG.

Because of the lack of prospective data in the field (5), we recently performed the CASCADE (Clopidogrel After Surgery for Coronary Artery Diseas E) study (NCT00228423), a randomized, placebo-controlled trial to evaluate whether the addition of clopidogrel to aspirin would inhibit the process of saphenous vein graft disease after CABG (6). Compared with aspirin alone, the combination of aspirin plus clopidogrel did not significantly reduce vein graft intimal hyperplasia 1 year after CABG, as assessed by intravascular ultrasound. Although CASCADE was not powered for angiographic or clinical outcomes, we also did not see a significant difference in vein graft patency or cardiovascular events between the 2 treatment groups (7). Power calculations based on CASCADE determined that a sample size of 8,000 grafts would be required to demonstrate an improvement in patency with clopidogrel. We doubt a future trial of this size will ever be performed.

In summary, based on the data available to date, we do not believe that compelling evidence exists to support the routine use of clopidogrel after CABG.