Abstract 12191: Efficacy and Safety of Vorapaxar in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Undergoing Non-Cardiac Surgery
Purpose: Perioperative antiplatelet agents potentially increase bleeding after a non-ST-segment elevation acute coronary syndrome (NSTE ACS). The PAR-1 antagonist vorapaxar reduced cardiovascular death, MI, or stroke and was associated with increased bleeding compared with placebo in NSTE ACS. Given vorapaxar’s long half-life and recent FDA approval, we evaluated its efficacy and safety after non-cardiac surgery (NCS) in NSTE ACS patients.
Methods: In the TRACER trial, 2202 (17.0%) NSTE ACS patients underwent NCS after randomization; continuing study treatment perioperatively was recommended. The primary endpoint for this analysis was 30-day perioperative cardiovascular death, MI, stent thrombosis, or urgent revascularization. Clinic events committee safety outcomes included 30-day NCS bleeding and GUSTO moderate/severe bleeding.
Results: Overall, 1171 vorapaxar and 1031 placebo patients underwent NCS at a median of 1.5 years. The timing of NCS after randomization was categorized as <30 days, 30 to 180 days, 180 days to 1 year, and >1 year and was 18.5%, 30.9%, 27.2%, and 23.4%, respectively. Preoperative aspirin and thienopyridine use was 96.8% vs. 97.7% (p=0.235) and 89.1% vs. 86.1% (p=0.036) for vorapaxar vs. placebo, respectively. A total of 270 (23.1%) vorapaxar and 207 (20.2%) placebo patients stopped study medication at a median of 13 and 15 days preoperatively. Within 30 days of NCS, no difference was observed for the primary composite endpoint in vorapaxar vs. placebo treatment (3.4% vs. 3.9%; adjusted OR 0.81, 95% CI 0.50-1.33; p=0.41). Similarly, no differences in the incidence of NCS bleeding (3.9% and 3.4%; adjusted OR 1.41, 95% CI 0.87-2.31; p=0.17) or GUSTO moderate/severe bleeding (4.2% vs. 3.7%; adjusted OR 1.15, 95% CI 0.72-1.83; p=0.55) were observed. At the end of the study, patients who underwent NCS had a higher overall incidence of GUSTO moderate/severe bleeding vs. those who did not undergo NCS (6.1% vs. 1.6%; adjusted HR 2.76, 95% CI 2.13-3.58; p≤0.01).
Conclusion: NCS after NSTE ACS is common and is associated with significant bleeding. Vorapaxar after NSTE ACS was not associated with increases in perioperative ischemic or bleeding events, thereby supporting the safety of vorapaxar in patients undergoing NCS.
Author Disclosures: S. van Diepen: None. P. Tricoci: Research Grant; Modest; Merck. Consultant/Advisory Board; Modest; Merck. M. Podder: None. P. Aylward: Research Grant; Modest; CSL Ltd, Glaxo Smith Kline, Merck Sharp and Dohme. Speakers Bureau; Modest; Bayer, Bristol Myer Squibb, The Medicine Company, Astra zeneca. Consultant/Advisory Board; Modest; The Medicine Company, Boehringer Ingelheim, Astra Zeneca. Research Grant; Significant; Astra Zeneca. C. Held: Research Grant; Modest; Roche, Schering-Plough (now Merck). Research Grant; Significant; AstraZeneca, GlaxoSmithKline, Pfizer/Bristol Myers Squibb. Consultant/Advisory Board; Modest; AstraZeneca. F. van de Werf: Research Grant; Significant; Merck. Honoraria; Modest; Merck. Consultant/Advisory Board; Modest; Merck. J. Strony: Employment; Significant; Merck & Co. K. Mahaffey: Consultant/Advisory Board; Modest; ACC, AstraZeneca, Bayer, Booehringer Ingelheim, BMS, Eli Lilly, Forest, Johnson & Johnson, Medtronic, Merck, Spring Publishing, The Medicines Company, Web MD. Consultant/Advisory Board; Significant; GlaxoSmithKline. R. Harrington: Employment; Significant; Merck, Astra, BMS, J and J. Consultant/Advisory Board; Modest; CSL, BMS, Daiichi, MyoKardia. Consultant/Advisory Board; Significant; Gilead, J and J, Merck. P. Armstrong: Employment; Significant; Merck & Company. Consultant/Advisory Board; Modest; Eli Lilly. Other; Modest; AstraZeneca.
- © 2014 by American Heart Association, Inc.