Combination oral antithrombotic therapy for the treatment of myocardial infarction: recent developments

ABSTRACT

Introduction: There have been significant new developments in the treatment of patients with myocardial infarction with respect to oral antithrombotic agents over the past decade. Recent studies have explored the potential utility of targeting the dual pathway inhibition of platelet function with single or dual antiplatelet agents and the thrombin pathway with direct thrombin inhibitors or factor Xa inhibitors.

Areas covered: In this review, the authors focus on the recent developments of oral antithrombotic agents including antiplatelet and antithrombin agents. It is based on literature covering: aspirin, P2Y₁₂ receptor blockers, PAR-1 inhibitors, direct thrombin inhibitors and factor Xa inhibitors from PubMed since 2008.

Expert opinion: Since thrombus formation involves multiple pathways including platelet activation and aggregation and coagulation, simultaneous and optimal blockade of these pathways is essential to prevent thrombotic complications and to avoid excessive bleeding in the myocardial infraction setting. Despite an improved anti-ischemic effect associated with potent P2Y₁₂ inhibitors plus aspirin, the degree of adverse event reduction compared to clopidogrel therapy in large scale trials is modest along with significantly greater bleeding. Recent studies suggest that targeting the thrombin pathway in addition to antiplatelet agents in high risk patients may further mitigate the risk of ischemic event occurrences with improved safety profiles.

KEYWORDS:

• Myocardial infarction
• platelet
• aspirin
• P2Y12 receptor inhibitor
• thrombin
• direct oral anticoagulant
• rivaroxaban

Article highlights

• The current standard of care for long term antiplatelet therapy in patients with myocardial infarction focus on the inhibition of the cyclooxygenase-1 pathway by aspirin and adenosine diphosphate-P2Y₁₂ pathways by P2Y₁₂ receptor inhibitors (clopidogrel, prasugrel, ticagrelor).

• However, despite high levels of blockade of these pathways by current therapy, treatment failure occurs in at least 10% of patients within a year of the index event and bleeding remains a serious side effect of therapy. These facts suggest that above strategy has reached a ceiling of net clinical benefit and spawned interest in targeting another pathway - ‘the thrombin pathway’.

• In addition to targeting platelet thrombin receptor (protease activated receptor −1) by vorapaxar, recent studies have focused on the safety and efficacy of direct oral anticoagulants for long term treatment in patients with myocardial infraction. The latter include direct thrombin inhibitor such as dabigatran or factor Xa inhibitors such as betrixaban, apixaban, and rivaroxaban.

• A very low dose of the Xa inhibitor, rivaroxaban, when added to aspirin and clopidogrel appears effective in reducing subsequent ischemic event occurrence with an acceptable bleeding rate to treat the stabilized ACS patient.

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Declaration of interest

P Gurbel reports receiving grants from the National Institutes of Health, Bayer Healthcare, Medicure, Instrumentation Labs, Haemonetics, Amgen Inc, Ionis, Idorsia, Janssen Pharmaceuticals and Merck & Co. He has also received honoraria and payment for lectures, consultations and for serving on speaker's bureaus from Bayer Healthcare, Janssen Pharmaceuticals, Merck & Co., Medicure and WorldMedicals. He also declares that he holds patents in personalized antiplatelet therapy and interventional cardiology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by Inova heart and Vascular Institute.