Usefulness and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (from the TRACER Trial).

Abstract

The therapeutic potential of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (PCI) is unknown. This prespecified analysis of a postrandomization subgroup evaluated the effects of vorapaxar compared with placebo among Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) participants undergoing PCI, focusing on the implanted stent type (drug-eluting stent [DES] vs bare-metal stent [BMS]). Among 12,944 recruited patients, 7,479 (57.8%) underwent PCI during index hospitalization, and 3,060 (40.9%) of those patients received exclusively BMS, whereas 4,015 (53.7%) received DES. The median (twenty-fifth, seventy-fifth percentiles) duration of thienopyridine therapy was 133 days (47, 246) with BMS and 221 days (88, 341) with DES. At 2 years among patients undergoing PCI, the primary (cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization) and secondary (cardiovascular death, myocardial infarction, or stroke) end points did not differ between vorapaxar and placebo groups, which was consistent with the treatment effect observed in the overall study population (p value for interaction = 0.540). However, the treatment effect trended greater (p value for interaction = 0.069) and the risk for bleeding in patients taking vorapaxar versus placebo appeared attenuated in BMS-only recipients. After adjustment for confounders, the interaction was no longer significant (p value = 0.301). The covariate that mostly explained the stent-type-by-treatment interaction was the duration of clopidogrel therapy. In conclusion, among patients with PCI, the effect of vorapaxar is consistent with the overall TRACER results. Patients who received a BMS underwent shorter courses of clopidogrel therapy and displayed trends toward greater ischemic benefit from vorapaxar and lesser bleeding risk, compared with patients who received a DES.

• Authors: Marco Valgimigli, Pierluigi Tricoci, Zhen Huang, Philip E Aylward, Paul W Armstrong, Frans Van de Werf, Sergio Leonardi, Harvey D White, Petr Widimsky, Robert A Harrington, Angel Cequier, Edmond Chen, Yuliya Lokhnygina, Lars Wallentin, John Strony, Kenneth W Mahaffey, David J Moliterno
• Journal: The American journal of cardiology (Am J Cardiol) Vol. 114 Issue 5 Pg. 665-73 (Sep 01 2014) ISSN: 1879-1913 [Electronic] United States
• PMID: 25129064 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Lactones
• Pyridines
• Receptors, Thrombin
• vorapaxar

Topics

• Acute Coronary Syndrome (drug therapy, physiopathology, surgery)
• Adult
• Aged
• Aged, 80 and over
• Australia (epidemiology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug-Eluting Stents
• Electrocardiography
• Europe (epidemiology)
• Female
• Follow-Up Studies
• Humans
• Incidence
• Injections, Intravenous
• Lactones (administration & dosage)
• Male
• Middle Aged
• Percutaneous Coronary Intervention (methods)
• Postoperative Complications (epidemiology)
• Prospective Studies
• Pyridines (administration & dosage)
• Receptors, Thrombin (antagonists & inhibitors)
• Survival Rate (trends)
• Treatment Outcome
• United States (epidemiology)