Author/Authors :
Whellan، نويسنده , , David J. and Tricoci، نويسنده , , Pierluigi and Chen، نويسنده , , Edmond and Huang، نويسنده , , Zhen and Leibowitz، نويسنده , , David and Vranckx، نويسنده , , Pascal and Marhefka، نويسنده , , Gregary D. and Held، نويسنده , , Claes and Nicolau، نويسنده , , Jose C. and Storey، نويسنده , , Robert F. and Ruzyllo، نويسنده , , Witold and Huber، نويسنده , , Kurt and Sinnaeve، نويسنده , , Peter A. Weiss، نويسنده , , A. Teddy and Dery، نويسنده , , Jean-Pierre and Moliterno، نويسنده , , David J. and Van de Werf، نويسنده , , Frans and Aylward، نويسنده , , Philip E. and White، نويسنده , , Harvey D. and Armstrong، نويسنده , , Paul W. and Wallentin، نويسنده , , Lars and Strony، نويسنده , , John A Harrington، نويسنده , , Robert A. and Mahaffey، نويسنده , , Kenneth W.، نويسنده ,
Abstract :
Objectives
tudy evaluated effects of protease-activated receptor-1 antagonist vorapaxar (Merck, Whitehouse Station, New Jersey) versus placebo among the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) study patients with non–ST-segment elevation acute coronary syndromes undergoing coronary artery bypass grafting (CABG).
ound
et activation may play a key role in graft occlusion, and antiplatelet therapies may reduce ischemic events, but perioperative bleeding risk remains a major concern. Although the TRACER study did not meet the primary quintuple composite outcome in the overall population with increased bleeding, an efficacy signal with vorapaxar was noted on major ischemic outcomes, and preliminary data suggest an acceptable surgical bleeding profile. We aimed to assess efficacy and safety of vorapaxar among CABG patients.
s
ations between treatment and ischemic and bleeding outcomes were assessed using time-to-event analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox hazards model. Event rates were estimated using the Kaplan-Meier method.
s
12,944 patients, 1,312 (10.1%) underwent CABG during index hospitalization, with 78% on the study drug at the time of surgery. Compared with placebo CABG patients, vorapaxar-treated patients had a 45% lower rate of the primary endpoint (i.e., a composite of death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization during index hospitalization) (HR: 0.55; 95% CI: 0.36 to 0.83; p = 0.005), with a significant interaction (p = 0.012). The CABG-related Thrombolysis In Myocardial Infarction major bleeding was numerically higher with vorapaxar, but not significantly different between vorapaxar and placebo (9.7% vs. 7.3%; HR: 1.36; 95% CI: 0.92 to 2.02; p = 0.12), with no excess in fatal bleeding (0% vs. 0.3%) or need for reoperation (4.7% vs. 4.6%).
sions
–ST-segment elevation acute coronary syndrome patients undergoing CABG, vorapaxar was associated with a significant reduction in ischemic events and no significant increase in major CABG-related bleeding. These data show promise for protease-activated receptor 1 antagonism in patients undergoing CABG and warrant confirmatory evidence in randomized trials. (Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Acute Coronary Syndrome [TRA·CER] [Study P04736AM3]; NCT00527943)
