Vorapaxar in ACS patients undergoing CABG surgery: results from the TRACER trial

Abstract

Purpose: The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial provided an opportunity to assess novel protease-activated receptor-1 antagonist vorapaxar in patients with NSTE ACS undergoing CABG surgery. Methods: This prespecified, post-randomization subgroup analysis evaluated the effects of vorapaxar compared with placebo among TRACER participants undergoing CABG surgery during their index hospitalization, from discharge to end of study. CABG-related TIMI major bleeding (adjudicated independently) was evaluated among treatment groups. Results: Among 12,944 TRACER patients, 1312 (10.1%) underwent CABG during the index hospitalization. The median age was 64 years and 78% of patients were male. The median time from loading dose to CABG was 120h with effect of single dose of vorapaxar lasting > 2 weeks. CABG patients treated with vorapaxar had a 45% reduction in the primary endpoint (composite of CV death, MI, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization) compared with placebo (HR, 0.55; 95% CI, 0.35–0.87; p=0.011). The interaction between treatment and CABG during the index hospitalization was statisti- cally significant (interaction p=0.02, Figure). CABG-related TIMI major bleeding was not statistically significantly different between vorapaxar and placebo (9.7 vs 7.3%; HR, 1.34; 95% CI, 0.92–1.95; p=0.13), with no excess in fatal bleeding or need for re-operation. Conclusions: In this unadjusted post-randomization subgroup analysis, NSTE ACS patients undergoing CABG and treated with vorapaxar had a 45% reduction in subsequent ischemic events. These findings are exploratory but support the opportunity for randomized trials of PAR-1 antagonism following CABG.