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Review
. 2015 Aug 3:11:1133-8.
doi: 10.2147/TCRM.S55469. eCollection 2015.

Clinical potential of vorapaxar in cardiovascular risk reduction in patients with atherosclerosis

Philipp Diehl  1 , Christoph Bode  1 , Daniel Duerschmied  1
Affiliations
Review

Clinical potential of vorapaxar in cardiovascular risk reduction in patients with atherosclerosis

Philipp Diehl et al. Ther Clin Risk Manag. .

Abstract

Vorapaxar (ZONTIVITY™, formerly known as SCH 530348) is a specific, orally active antagonist of the protease-activated receptor-1 (PAR-1) on platelets. It inhibits thrombin-induced platelet activation by binding to the ectodomain of PAR-1. After animal studies and Phase II studies showed that vorapaxar sufficiently inhibits platelet activation without significantly increasing bleeding complications, safety and efficacy of vorapaxar were assessed in two large multicenter trials in patients with coronary artery disease and atherosclerosis. The Thrombin-Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndromes (TRACER) trial investigated safety and efficacy of vorapaxar in patients with an acute coronary syndrome without ST-segment elevation. The Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis In Myocardial Infarction 50 (TRA 2°P-TIMI 50) investigated atherothrombotic events in patients with stable atherosclerosis. Results of both studies suggested that vorapaxar given in addition to standard antiplatelet therapy can reduce atherothrombotic events, but increases the risk of mild and moderate bleeding complications. This review article summarizes the main results of TRACER and TRA 2°P-TIMI 50 and suggests patient cohorts that might benefit from treatment with vorapaxar in addition to standard antiplatelet therapy.

Keywords: antiplatelet therapy; atherosclerosis; myocardial infarction; vorapaxar.

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Figures

Figure 1
Figure 1
Mechanistic illustration of the PAR-1 and PAR-4. Notes: Thrombin cleaves a silencing domain of the proteinase activated receptor. The new receptors’ N-terminus can now bind to a second receptor ectodomain resulting in an outside-in signaling of PAR. Vorapaxar specifically inhibits cleavage of the silencing peptide of PAR-1. However, higher concentrations of thrombin still can induce platelet activation via PAR-4. Abbreviations: PAR, protease activated receptor; ADP, adenosine diphosphate.
See this image and copyright information in PMC

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