Potential role of oral anticoagulants in the treatment of patients with coronary artery disease: focus on dabigatran

Abstract

The pharmacologic management of patients with high-risk coronary artery disease consists of aspirin and a P2Y₁₂ receptor inhibitor. Chronic oral anticoagulation with warfarin is the major treatment strategy to attenuate thromboembolism or stroke in patients with deep vein thrombosis, pulmonary embolism, heart failure and atrial fibrillation. A substantial percentage of the latter group of patients have coronary artery disease and may require stenting with long-term dual antiplatelet therapy in addition to therapy with warfarin to reduce arterial ischemic events in addition to stroke. These new oral anticoagulants have been developed for long-term therapy to overcome the limitations of warfarin. Dabigatran is a direct thrombin inhibitor and its role in patients with acute coronary syndrome is being explored.

Keywords::

• acute coronary syndromes
• antiplatelet agents
• apixaban
• aspirin
• clopidogrel
• dabigatran
• oral anticoagulants
• P2Y₁₂ receptor blockers
• rivaroxaban
• warfarin

Financial & competing interests disclosure

PA Gurbel serves as a consultant for Daiichi Sankyo, Sankyo, Lilly, Pozen, Novartis, Bayer, AstraZeneca, Accumetrics, Nanosphere, Sanofi-Aventis, Boehringer Ingelheim, Merck, Medtronic, Iverson Genetics, CSL and Haemonetics; receiving grants from the National Institutes of Health, Daiichi Sankyo, Lilly, Pozen, CSL, AstraZeneca, Sanofi-Aventis, Haemoscope, Medtronic, Harvard Clinical Research Institute and Duke Clinical Research Institute; receiving payment for lectures, including service on speakers’ bureaus, from Lilly, Daiichi Sankyo, Nanosphere, Sanofi-Aventis, Merck and Iverson Genetics; receiving payment for development of educational presentations from Merck, the Discovery Channel and Pri-Med; holding stock or stock options in Merck, Medtronic and Pfizer; and holding patents in the area of personalized antiplatelet therapy and interventional cardiology. MJ Slepian serves as a consultant to Merck, Sanofi-Aventis, Pfizer, Lily, Otsuka and Jannsen: receiving grant support from the National Institutes of Health, is a founder of SynCardia, MC10, and PolyNova, holding stock or stock options in Arsenal and 480 BioMedical; and holding patents in the area of biodegradable stents and scaffolds, novel biomaterials, prosthetic heart valves and mechanical circulatory support. 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • In acute coronary syndrome (ACS) patients with an indication for long-term treatment with oral anticoagulant therapy in addition to dual antiplatelet therapy (TRIPLE therapy), newer anticoagulants are promising as credible alternatives to warfarin.

• • The new oral anticoagulants have been developed for long-term therapy to overcome the limitations of warfarin.

• • Although enhanced bleeding can be expected with the addition of any new anticoagulant to dual antiplatelet therapy, it may not be significantly worse than warfarin.

• • With the absence of any antidote to oral anticoagulants at this time, monitoring and reversal of effects are big challenges for widespread treatment of oral anticoagulants.

• • Dabigatran is a direct thrombin inhibitor and its role in patients with ACS is being explored. At this time, there are no conclusive data to support the use of dabigatran over warfarin in ACS patients.

• • Large-scale prospective studies are required to assess the utility of ‘guided TRIPLE therapy’ based on platelet function testing and oral anticoagulant therapy monitoring to maximize the efficacy and safety.

Notes