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Risks and Benefits of Triple Oral Anti-Thrombotic Therapies After Acute Coronary Syndromes and Percutaneous Coronary Intervention

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Abstract

The key pathophysiological process underlying symptomatic coronary artery disease, including acute coronary syndromes (ACS), is usually a rupture or an erosion of an atherosclerotic plaque, followed by platelet activation and subsequent thrombus formation. Early clinical trials showed benefit with long-term aspirin treatment, and later—based on large clinical trials—dual anti-platelet therapy (DAPT), initially with clopidogrel, and more recently with prasugrel or ticagrelor, has become the established treatment in the post-ACS setting and after percutaneous coronary intervention (PCI). Treatment with DAPT is recommended for both ST-elevation myocardial infarction and non-ST-elevation ACS, as well as after PCI with stenting, in American and European clinical guidelines. Notwithstanding the benefits observed with DAPT, including third-generation P2Y12 receptor inhibitors plus aspirin, ACS patients remain at high risk for a recurrent cardiovascular event, suggesting that other treatment strategies, including the addition of a third oral anti-platelet agent or a novel oral anticoagulant (NOAC) to standard DAPT regimens, may provide additional benefit for post-ACS patients and for patients undergoing PCI. Adding a third anti-thrombotic agent to DAPT after an ACS event or a PCI procedure has been shown to have modest benefit in terms of ischemic event reduction, but has consistently been associated with increased bleeding complications. Therefore, the quest to optimize anti-thrombotic therapies post-ACS and post-PCI continues unabated but is tempered by the historical experiences to date that indicate that careful patient and dose selection will be critical features of future randomized trials.

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Acknowledgments

This manuscript was co-written entirely by the authors with no external funding support. Dr. Joakim Alfredsson has consulted for Bristol-Meyers Squibb, Sanofi-Aventis, and Eli-Lilly and has received lecture fees from Astra-Zeneca, Novartis, Merck, Sharp & Dome, and Sanofi-Aventis. Dr. Matthew Roe has received research funding from Eli Lilly, Sanofi-Aventis, Amgen, Daiichi-Sanko, Janssen Pharmaceuticals, Ferring Pharmaceuticals, the ACC, the AHA, and the Familial Hypercholesterolemia Foundation, and has consulted for or received honoraria from Astra Zeneca, Boehringer-Ingelheim, Merck, Amgen, and Elsevier Publishers. All conflicts of interest are listed online at https://www.dcri.org/about-us/conflict-of-interest.

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  1. Department of Cardiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden

    Joakim Alfredsson

  2. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA

    Joakim Alfredsson & Matthew T. Roe

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Correspondence to Joakim Alfredsson.

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Alfredsson, J., Roe, M.T. Risks and Benefits of Triple Oral Anti-Thrombotic Therapies After Acute Coronary Syndromes and Percutaneous Coronary Intervention. Drug Saf 38, 481–491 (2015). https://doi.org/10.1007/s40264-015-0286-8

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