Context Thienopyridines are among the most widely prescribed medications, but their use can be complicated by the unanticipated need for surgery. Despite increased risk of thrombosis, guidelines recommend discontinuing thienopyridines 5–7 days prior to surgery to minimize bleeding. Objective To evaluate the use of cangrelor, an intravenous, reversible P2Y12 platelet inhibitor for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG). Design, Setting, and Patients Prospective, randomized double-blind, placebo-controlled, multicenter trial, in patients (n=210) with an acute coronary syndrome (ACS) or treated with a coronary stent on a thienopyridine awaiting CABG to receive either cangrelor or placebo after an initial open-label, dose-finding phase (n=11) conducted between January 2009 and April 2011. Interventions Thienopyridines were stopped and patients administered cangrelor or placebo for at least 48 hours, which was discontinued 1–6 hours prior to CABG. Main outcome measures The primary efficacy endpoint was platelet reactivity (measured in P2Y12 Reaction Units [PRU]), assessed daily with the VerifyNow™ P2Y12 assay. The main safety endpoint was excessive CABG-related bleeding. Results The dose of cangrelor determined in the open-label stage was 0.75 µg/kg/min. In the randomized phase, a greater proportion of patients treated with cangrelor had low levels of platelet reactivity throughout the entire treatment period compared with placebo (primary endpoint, PRU<240: 98.8% (83/84) vs. 19.0% (16/84); relative risk [RR]: 5.2, 95% confidence interval [CI]:3.3–8.1, p<0.001). Excessive CABG-related bleeding occurred in 11.8% (12/102) vs. 10.4% (10/96) in the cangrelor and placebo groups, respectively (RR=1.1, 95% CI: 0.5–2.5, p=0.763). There were no significant differences in major bleeding prior to CABG, although minor bleeding was numerically higher with cangrelor. Conclusions Among patients who must wait for cardiac surgery after thienopyridine discontinuation, the use of cangrelor compared with placebo resulted in a higher rate of maintenance of platelet inhibition.

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