Antiplatelet options for secondary prevention in acute coronary syndromes

Abstract

Current guidelines recommend dual antiplatelet therapy, a combination of aspirin and a P2Y₁₂ inhibitor, for 6–12 months after percutaneous coronary intervention with drug-eluting stent implantation in all patients and for 1 year in all patients after an acute coronary syndrome (ACS), irrespective of revascularization strategy. Clopidogrel has a pharmacokinetic and pharmacodynamic profile that results in a delayed and/or subtherapeutic antiplatelet effect, and wide variability in antiplatelet response. New P2Y₁₂ inhibitors, such as prasugrel and ticagrelor, have favorable pharmacodynamics and clinical efficacy over clopidogrel and offer an alternative antiplatelet treatment strategy in specific patients. Prasugrel has more potent, rapid, and consistent effects on inhibiting ADP-induced platelet aggregation than clopidogrel. Ticagrelor also appears to have more rapid and consistent antiplatelet effects than clopidogrel. The higher levels of antiplatelet inhibition provided by prasugrel and ticagrelor compared with standard-dose clopidogrel result in improved ischemic outcomes in patients with ACS. Despite an increase in bleeding risk, prasugrel and ticagrelor appear to have a better net clinical benefit, especially in higher-risk patients with ACS.

Keywords::

• acute coronary syndrome
• antiplatelet therapy
• clopidogrel
• prasugrel
• ticagrelor

Financial & competing interests disclosure

Johanne Silvain has received research grants from sanofi-aventis, Daiichi-Sankyo, Eli Lilly, INSERM, Fédération Française de Cardiologie and Société Française de Cardiologie, consultant fees from Daiichi-Sankyo and Eli Lilly and lecture fees from AstraZeneca, Daiichi-Sankyo and Eli Lilly. Guillaume Cayla has received research grants from sanofi-aventis and Fédération Française de Cardiologie, has served as a consultant to Eli Lilly and Daiichi Sankyo and has received lecture fees from Eli Lilly, Daiichi Sankyo, Servier and Abbott. Stephen A O’Connor has received research grant support from A Menarini and the European Society of Cardiology. Jean-Philippe Collet has received research grants from Bristol-Myers Squibb, sanofi-aventis, Eli Lilly, Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, Centocor, Fondation de France, INSERM, Fédération Française de Cardiologie, and Société Française de Cardiologie has received consulting fees from sanofi-aventis, Eli Lilly and Bristol-Myers Squibb and lecture fees from Bristol-Myers Squibb, sanofi-aventis and Eli Lilly. Gilles Montalescot has received research grants from Abbott Vascular, AstraZeneca, Bristol-Myers Squibb, Boston Scientific, Cordis, Eli Lilly, Fédération Française de Cardiologie, Fondation de France, Guerbet Medical, INSERM, ITC Edison, Medtronic, Pfizer, sanofi-aventis, Servier, Société Française de Cardiologie, Stago and consulting or lectures fees from AstraZeneca, Bayer, Boehringer Ingelheim, Cardiovascular Research Foundation, Cleveland Clinic Research Foundation, Daiichi-Sankyo, Duke Institute, Eli Lilly, Europa, Lead-Up, GlaxoSmithKline, Institut de Cardiologie de Montréal, Menarini, Nanospheres, Novartis, Pfizer, Portola, sanofi-aventis, The Medicines Company and Thrombolysis in Myocardial Infarction study group. 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.

Medical writing assistance was provided by Raelene Simpson, Blair Jarvis, and Mary Hines of Adis Communications through financial support from Daiichi Sankyo, Inc., and Eli Lilly and Company.