Key result
Vorapaxar reduced the composite of cardiovascular death, myocardial infarction, or stroke by 13% compared to placebo in patients with a history of myocardial infarction, ischemic stroke, or peripheral artery disease.
Why the study?
Does vorapaxar reduce thrombotic cardiovascular events in patients with prior myocardial infarction or peripheral artery disease?
Does vorapaxar reduce thrombotic cardiovascular events in patients with prior myocardial infarction or peripheral artery disease?
Effect estimate: HR 0.87 (95% CI 0.80-0.94)
Absolute Event Rate: 9.3% vs 10.5%
p-value: p=<0.001
Vorapaxar reduces thrombotic cardiovascular events in patients with prior MI or PAD but increases bleeding risk, necessitating careful patient selection.
Requires careful patient selection due to bleeding risk; leaves open net benefit questions in contemporary regimens.
Vorapaxar specifically and effectively inhibits protease activated receptor-1 and may reduce thrombin-mediated ischemic events without interfering primary hemostasis. In the TRA-2P-TIMI 50 trial, vorapaxar reduced the risk of primary ischemic outcome but with increased bleeding risk. In the post hoc analysis, in patients with a history of myocardial infarction, peripheral artery disease, the net clinical outcome favored vorapaxar therapy with 10% reduction in cardiovascular death, myocardial infarction, stroke, urgent coronary revascularization and moderate or severe bleeding. Based on these favorable results, vorapaxar was approved for the reduction of thrombotic cardiovascular events in patients with prior myocardial infarction or with peripheral artery disease on top of standard antiplatelet therapy. A careful patient selection is needed to balance efficacy versus safety.
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Tantry et al. (2020) conducted a review in Stable disease with a history of myocardial infarction, ischemic stroke, or peripheral artery disease (n=26,449). Vorapaxar vs. Placebo was evaluated on Composite of cardiovascular death, myocardial infarction, or stroke (HR 0.87, 95% CI 0.80-0.94, p=<0.001). Vorapaxar reduced the composite of cardiovascular death, myocardial infarction, or stroke by 13% compared to placebo in patients with a history of myocardial infarction, ischemic stroke, or peripheral artery disease.
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