PAR-1 Antagonists: An Emerging Antiplatelet Drug Class

Review
In: CADTH Issues in Emerging Health Technologies. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016. 148.
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Excerpt

  1. Protease-activated receptor-1 (PAR-1) antagonists are known to be potent antiplatelet agents that are also complementary to other antiplatelet therapies. Vorapaxar and atopaxar are currently the two PAR-1 antagonist antiplatelet agents that have undergone extensive clinical development.

  2. Phase 3 clinical evidence is available for vorapaxar and supports its use for the reduction of thrombotic cardiovascular events in higher-risk patients with a history of myocardial infarction (MI) or peripheral artery disease (PAD). The trials examined the addition of vorapaxar to acetylsalicylic acid (ASA) and/or P2Y12 receptor antagonists (dual and triple antiplatelet therapy) to reduce the combined end point of cardiovascular death, MI, stroke, and urgent coronary revascularization. Bleeding risk remains a concern, according to the available clinical data. In order keep a positive balance between the clinical effect and the bleeding risks, careful patient selection will be needed.

  3. Phase 2 clinical evidence is available for atopaxar administered in combination with ASA and/or P2Y12 receptor antagonists. These trials reported an increased bleeding risk, although such risk seems to be limited to less severe bleeding complications. Other adverse events such as liver and cardiac toxicities may affect the future development of this drug.

  4. Although current available evidence limits the use of vorapaxar to a subgroup of patients with a history of MI or PAD, more clinical studies are planned for the near future; these may potentially lead to additional indications.

Publication types

  • Review