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TRA 2°P-TIMI 50 Trial : Vorapaxar for Secondary Prevention after Myocardial Infarction


Presenter: Benjamin Morgan Scirica | see Discussant report




Vorapaxar inhibits platelet activation by antagonising thrombin-mediated activation of the protease activated receptor 1 on human platelets. The effect of adding other antiplatelet drugs to aspirin for long-term secondary prevention of thrombotic events in stable patients with previous myocardial infarction is uncertain. We tested this effect in a subgroup of patients from the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-TIMI 50 trial.

In TRA 2°P-TIMI 50—a randomised, placebo-controlled, parallel trial—we randomly assigned patients with a history of atherothrombosis to receive vorapaxar (2·5 mg daily) or matching placebo in a 1:1 ratio. Patients, and those giving treatment, assessing outcomes, and analysing results were masked to treatment allocation. Patients with a qualifying myocardial infarction within the previous 2 weeks to 12 months were analysed as a pre-defined subgroup. The primary efficacy endpoint was cardiovascular death, myocardial infarction, or stroke, analysed by intention to treat. We analysed events by Kaplan-Meier analysis and compared groups with a Cox proportional hazard model.
TRA 2°P-TIMI 50 is registered at (NCT00526474).

17 779 of 26 449 patients had a qualifying myocardial infarction and were assigned treatment (8898 to vorapaxar and 8881 to placebo). Median follow-up was 2·5 years (IQR 2·0–2·9). Cardiovascular death, myocardial infarction, or stroke occurred in 610 of 8898 patients in the vorapaxar group and 750 of 8881 in the placebo group (3-year Kaplan-Meier estimates 8·1% vs 9·7%, HR 0·80, 95% CI 0·72–0·89; p<0·0001). Moderate or severe bleeding was more common in the vorapaxar group versus the placebo group (241/8880 [3·4%, 3-year Kaplan-Meier estimate] vs 151/8849 [2·1%, 3-year Kaplan-Meier estimate], HR 1·61, 95% CI 1·31–1·97; p<0·0001). Intracranial haemorrhage occurred in 43 of 8880 patients (0·6%, 3-year Kaplan-Meier estimate) with vorapaxar versus 28 of 8849 (0·4%, 3-year Kaplan-Meier estimate) with placebo (p=0·076). Other serious adverse events were equally distributed between groups.

Patients aged younger than 75 years, with no history of transient ischaemic attack or stroke, and bodyweight at least 60 kg might have the best potential for net clinical benefit with intense antiplatelet therapy.In such patients (n=14 909, 84% of previous myocardial infarction population), cardiovascular death, myocardial infarction, or stroke was less common in the vorapaxar than in the placebo group (431/7449 [6.8%, 3-year Kaplan-Meier estimate] vs 570/7460 [8.6%, 3-year Kaplan-Meier estimate], HR 0.75, 95% CI 0.66–0.85; p<0.0001), as was cardiovascular death (92/7449 [1.5%, 3-year Kaplan-
Meier estimate] vs 126/7460 [2.0%, 3-year Kaplan-Meier estimate], HR 0.73, 0.56–0.95; p=0.020).

For patients with a history of myocardial infarction, inhibition of protease-activated receptor 1 with vorapaxar reduces the risk of cardiovascular death or ischaemic events when added to standard antiplatelet treatment, including aspirin, and increases the risk of moderate or severe bleeding.

Discussant: Christoph Bode | see Presenter abstract 



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Clinical Trial & Registry Update I: Updates on Prevention and Markers

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.