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.

Document Type

Article

Publication Date

12-18-2018

Notes/Citation Information

Published in Journal of the American Heart Association, v. 7, issue 24, e009609, p. 1-10.

© 2018 The Authors. Published on behalf of the American Heart Association,Inc., by Wiley.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Digital Object Identifier (DOI)

https://doi.org/10.1161/JAHA.118.009609

Funding Information

The TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial was funded by Merck & Co.

Related Content

An accompanying Figure S1 is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.118.009609.

Melloni had full access to all the data in the study and takes responsibility for its integrity and the data analysis.

jah33709-sup-0001-figs1.pdf (396 kB)
Supplemental Material: Figure S1.

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