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Effect of vorapaxar on myocardial infarction in the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRA·CER) trial
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2013 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 23, 1723-1731 p.Article in journal (Refereed) Published
Abstract [en]


The TRA·CER trial compared vorapaxar, a novel platelet protease-activated receptor (PAR)-1 antagonist, with placebo in 12 944 patients with high-risk non–ST-segment elevation acute coronary syndromes (NSTE ACS). In this analysis, we explored the effect of vorapaxar on myocardial infarction (MI).

Methods and results

A blinded, independent central endpoint adjudication committee prospectively defined and classified MI according to the universal MI definition, including peak cardiac marker value (creatine kinase-MB [CK-MB] and/or troponin). Because the trial failed to meet its primary endpoint, these analyses are considered exploratory. During a median follow-up of 502 days, 1580 MIs occurred in 1319 patients. The majority (n = 1025, 64.9%) were type 1 (spontaneous) MI, followed by type 4a [percutaneous coronary intervention (PCI)-related] MI (n = 352; 22.3%). Compared with placebo, vorapaxar reduced the hazard of a first MI of any type by 12% [hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.79–0.98; P = 0.021] and the hazard of total number of MIs (first and subsequent) by 14% (HR, 0.86; 95% CI, 0.77–0.97; P = 0.014), an effect that was sustained over time. Vorapaxar reduced type 1 MI by 17% (HR, 0.83; 95% CI, 0.73–0.95; P = 0.007). Type 4a MIs were not significantly reduced by vorapaxar (HR, 0.90; 95% CI, 0.73–1.12; P = 0.35). Vorapaxar effect was consistent across MI sizes defined by peak cardiac marker elevations and across key clinical subgroups; however, in patients not treated with thienopyridine at baseline (HR, 0.65; 95% CI, 0.46–0.92) compared with patients who received thienopyridine (HR, 0.91; 95% CI, 0.81–1.02), there was a trend towards a higher effect (Pint = 0.077).


The PAR-1 antagonist vorapaxar was associated with a reduction of MI, including total number of infarctions. This reduction was sustained over time and was mostly evident in type 1 MI, the most common type of MI observed.

Place, publisher, year, edition, pages
2013. Vol. 34, no 23, 1723-1731 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-198306DOI: 10.1093/eurheartj/eht104ISI: 000320408500009PubMedID: 23530022OAI: oai:DiVA.org:uu-198306DiVA: diva2:615706
Available from: 2013-04-11 Created: 2013-04-11 Last updated: 2013-07-22Bibliographically approved

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Wallentin, LarsHeld, Claes
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UCR-Uppsala Clinical Research CenterCardiologyDepartment of Medical Sciences
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