Stroke Outcomes With Vorapaxar Versus Placebo in Patients With Acute Coronary Syndromes: Insights From the TRACER Trial.

Abstract

Background Vorapaxar, a protease-activated receptor-1 antagonist, is approved for secondary prevention of cardiovascular events but is associated with increased intracranial hemorrhage. Methods and Results TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) was a trial of vorapaxar versus placebo among patients with acute coronary syndrome. Strokes were adjudicated by a central events committee. Of 12 944 patients, 199 (1.5%) had ≥1 stroke during the study period (median follow-up, 477 days). Four patients had a single stroke of unknown type; 195 patients had ≥1 stroke classified as hemorrhagic or nonhemorrhagic (165 nonhemorrhagic, 28 hemorrhagic, and 2 both). Strokes occurred in 96 of 6473 patients (1.5%) assigned vorapaxar and 103 of 6471 patients (1.6%) assigned placebo. Kaplan-Meier incidence of stroke for vorapaxar versus placebo was higher for hemorrhagic stroke (0.45% versus 0.14% [hazard ratio, 2.74; 95% confidence interval, 1.22-6.15]), lower but not significantly different for nonhemorrhagic stroke (1.53% versus 1.98% at 2 years [hazard ratio, 0.79; 95% confidence interval, 0.58-1.07]), and similar for stroke overall (1.93% versus 2.13% at 2 years [hazard ratio, 0.94; 95% confidence interval, 0.71-1.24]). Conclusions Stroke occurred in <2% of patients. Vorapaxar-assigned patients had increased hemorrhagic stroke but a nonsignificant trend toward lower nonhemorrhagic stroke. Overall stroke frequency was similar with vorapaxar versus placebo.

• Authors: Leo Ungar, Robert M Clare, Fatima Rodriguez, Bradley J Kolls, Paul W Armstrong, Philip Aylward, Claes Held, David J Moliterno, John Strony, Frans Van de Werf, Lars Wallentin, Harvey D White, Pierluigi Tricoci, Robert A Harrington, Kenneth W Mahaffey, Chiara Melloni
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 7 Issue 24 Pg. e009609 (12 18 2018) ISSN: 2047-9980 [Electronic] England
• PMID: 30526198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lactones
• Platelet Aggregation Inhibitors
• Pyridines
• vorapaxar

Topics

• Acute Coronary Syndrome (diagnosis, drug therapy, epidemiology)
• Aged
• Clinical Trials, Phase III as Topic
• Female
• Humans
• Incidence
• Intracranial Hemorrhages (chemically induced, diagnostic imaging, epidemiology)
• Lactones (adverse effects)
• Male
• Middle Aged
• Multicenter Studies as Topic
• Platelet Aggregation Inhibitors (adverse effects)
• Pyridines (adverse effects)
• Randomized Controlled Trials as Topic
• Recurrence
• Risk Assessment
• Risk Factors
• Secondary Prevention (methods)
• Stroke (chemically induced, diagnostic imaging, epidemiology)
• Treatment Outcome