Vorapaxar, a platelet thrombin-receptor antagonist, in medically managed patients with non-ST-segment elevation acute coronary syndrome: results from the TRACER trial.

Abstract

BACKGROUND:

This study characterized a medically managed population in a non-ST-segment elevation acute coronary syndrome (NSTEACS) cohort and evaluated prognosis and outcomes of vorapaxar vs. placebo.

METHODS:

In the TRACER study, 12,944 NSTEACS patients were treated with standard care and vorapaxar (a novel platelet protease-activated receptor-1 antagonist) or placebo. Of those, 4194 patients (32.4%) did not undergo revascularization during index hospitalization, and 8750 (67.6%) underwent percutaneous coronary intervention or coronary artery bypass grafting. Patients managed medically were heterogeneous with different risk profiles, including 1137 (27.1%) who did not undergo coronary angiography. Patients who underwent angiography but were selected for medical management included those without evidence of significant coronary artery disease (CAD), with prior CAD but no new significant lesions, and with significant lesions who were not treated with revascularization.

RESULTS:

Cardiovascular event rates were highest among those without angiography and lowest in the group with angiography but without CAD. In the medically managed cohort, 2-year primary outcome (cardiovascular death, myocardial infarction, stroke, recurrent ischaemia with rehospitalization, urgent coronary revascularization) event rates were 16.3% with vorapaxar and 17.0% with placebo (HR 0.99, 95% CI 0.83-1.17), with no interaction between drug and management strategy (p=0.75). Key secondary endpoint (cardiovascular death, myocardial infarction, stroke) rates were 13.4% with vorapaxar and 14.9% with placebo (HR 0.89, 95% CI 0.74-1.07), with no interaction (p=0.58). Vorapaxar increased GUSTO moderate/severe bleeding numerically in medically managed patients (adjusted HR 1.46, 95% CI 0.99-2.15).

CONCLUSIONS:

NSTEACS patients who were initially medically managed had a higher risk-factor burden, and one-third had normal coronary arteries. Outcome in the medically managed cohort was significantly related to degree of CAD, highlighting the importance of coronary angiography. Efficacy and safety of vorapaxar appeared consistent with the overall trial results.

• Authors: Claes Held, Pierluigi Tricoci, Zhen Huang, Frans Van de Werf, Harvey D White, Paul W Armstrong, Giuseppe Ambrosio, Philip E Aylward, David J Moliterno, Lars Wallentin, Edmond Chen, Aycan Erkan, Lixin Jiang, John Strony, Robert A Harrington, Kenneth W Mahaffey
• Journal: European heart journal. Acute cardiovascular care (Eur Heart J Acute Cardiovasc Care) Vol. 3 Issue 3 Pg. 246-56 (Sep 2014) ISSN: 2048-8734 [Electronic] England
• PMID: 24627331 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The European Society of Cardiology 2014.

Chemical References

• Lactones
• Platelet Aggregation Inhibitors
• Pyridines
• vorapaxar

Topics

• Acute Coronary Syndrome (drug therapy)
• Aged
• Double-Blind Method
• Female
• Hemorrhage (etiology)
• Humans
• Lactones (therapeutic use)
• Male
• Middle Aged
• Myocardial Infarction (etiology)
• Platelet Aggregation Inhibitors (therapeutic use)
• Pyridines (therapeutic use)
• Recurrence
• Risk Factors
• Stroke (etiology)
• Treatment Outcome