Safety of Clopidogrel Being Continued Until the Time of Coronary Artery Bypass Grafting in Patients With Acute Coronary Syndrome: A Meta-Analysis of 34 Studies

Study Questions:

What is the risk of mortality, reoperation, perioperative myocardial infarction (MI), and stroke in the acute coronary syndrome (ACS) population undergoing coronary artery bypass grafting (CABG) while on clopidogrel?

Methods:

Thirty-four studies with 22,584 patients undergoing CABG were assessed. Patients with recent clopidogrel exposure (CL) were compared with those without recent clopidogrel (NC). Uni- and multivariate meta-regression was performed for the main outcomes of mortality, reoperation, postoperative MI, and stroke using the logarithm of the odds ratio (OR) as the dependent variable. Interaction analysis was performed creating interaction terms between the variable ACS status and the following variables: year of study, the use of on-pump surgery, patient urgency status, and use of concomitant antiplatelet agents, including aspirin and glycoprotein IIb/IIIa antagonists.

Results:

Although mortality is increased in CL versus NC (OR, 1.6; 95% confidence interval [CI], 1.30-1.96; p < 0.00001), it is influenced by the ACS status and case urgency in these mainly nonrandomized studies. In ACS patients, there is no significant difference in mortality (OR, 1.44; 95% CI, 0.97-2.1; p = 0.07) or in postoperative MI (OR, 0.57; 95% CI, 0.31-1.07; p = 0.08) and stroke rates (OR, 1.23; 95% CI, 0.66-2.29; p = 0.52). Combined major adverse cardiovascular events (MACE) (stroke, MI, and death) were not different in the two groups (OR, 1.10; 95% CI, 0.87-1.41; p = 0.43). Reoperation rates are elevated on clopidogrel but have reduced over time, and were specifically not different in ACS patients (OR, 1.5; 95% CI, 0.88-2.54; p = 0.13).

Conclusions:

The authors concluded that ACS patients requiring urgent CABG proceed with surgery without delay for a clopidogrel-free period.

Perspective:

This meta-analysis suggests that continuing dual antiplatelet therapy until the day of CABG reduces the risk of recurrent ischemic events in ACS patients and reduces MI postoperatively. While mortality and reoperation rates are increased after recent clopidogrel exposure, event rates were still low and overall MACE rates did not appear to be significantly increased in the clopidogrel group. These data demonstrate the need for a randomized clinical trial assessing different discontinuation times prior to CABG to definitively answer the question. Meanwhile, the evidence appears to suggest that many ACS patients can undergo CABG safely with recent clopidogrel exposure in expert hands.

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Stroke, Platelet Aggregation Inhibitors, Coronary Artery Bypass


< Back to Listings