Author + information
- Received June 7, 2013
- Accepted June 20, 2013
- Published online November 1, 2013.
- Jolanta M. Siller-Matula, MD, PhD∗∗ (, )
- Dietmar Trenk, PhD†,
- Karsten Schrör, MD‡,
- Meinrad Gawaz, MD§,
- Steen D. Kristensen, MD‖,
- Robert F. Storey, MD¶,
- Kurt Huber, MD#,
- EPA (European Platelet Academy)
- ∗Department of Cardiology, Medical University of Vienna, Vienna, Austria
- †Clinics of Cardiology and Angiology II, Universitäts-Herzzentrum Freiburg Bad Krozingen, Bad Krozingen, Germany
- ‡Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany
- §Medizinische Klinik III, Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University, Tübingen, Germany
- ‖Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
- ¶Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom
- #3rd Medical Department, Cardiology and Emergency Medicine, Wilhelminenhospital, Vienna, Austria
- ↵∗Reprint requests and correspondence:
Dr. Jolanta M. Siller-Matula, Department of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
P2Y12 inhibitors are widely used in patients with acute coronary syndromes and in the secondary prevention of thrombotic events in vascular diseases. Within the past few years, several pharmacological, genetic, and clinical limitations of the second-generation thienopyridine clopidogrel have raised major concerns. High on-treatment platelet reactivity, which is common in clopidogrel-treated patients, and its clinical implications led to the development of the more effective platelet P2Y12 inhibitors prasugrel (a third-generation thienopyridine) and ticagrelor (a cyclopentyl-triazolo-pyrimidine). The pharmacokinetics and pharmacodynamics of prasugrel and ticagrelor indicate that they provide more consistent, more rapid, and more potent platelet inhibition than clopidogrel, which translates into improved ischemic outcomes. Nevertheless, higher efficacy, which is reflected by low on-treatment platelet reactivity, increases the risk of major bleeding events. Therefore, cardiologists might be facing a new challenge in the future: to individualize the level of platelet inhibition in order to decrease thrombotic events without increasing bleeding. The current review focuses on the use of platelet function testing and pharmacogenomic testing in order to identify patients who either do not respond to or are at risk of not responding sufficiently to P2Y12 inhibitors. Moreover, this paper discusses randomized trials, which so far have failed to show that tailored antiplatelet therapy improves clinical outcome, and treatment options for patients with high on-treatment platelet reactivity.
Dr. Siller-Matula has received lecture or consultant fees from AstraZeneca, Daiichi Sankyo, and Eli Lilly and Company; and a research grant from Roche. Prof. Trenk has received consultant fees or advisory board fees from Eli Lilly and Company, Daiichi Sankyo, and AstraZeneca; and lecture fees from Eli Lilly and Company Daiichi Sankyo, AstraZeneca, Boehringer Ingelheim KG, and Bayer. Prof. Schrör has received lecture or consultant fees from AstraZeneca, Bayer, Eli Lilly and Company/Daiichi Sankyo, and Iroko Pharmaceuticals; and is on the advisory boards of Eli Lilly and Company and Bayer. Prof. Gawaz has received lecture fees from AstraZeneca, Bayer Vital, Boehringer Ingelheim, Daiichi Sankyo, and Eli Lilly and Company. Prof. Kristensen has received lecture fees from AstraZeneca, Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, Eli Lilly and Company, Iroko Pharmaceuticals, Merck & Co., Pfizer, Sanofi, and The Medicines Company. Prof. Storey has received honoraria, consultanct fees, and/or institutional grants from AstraZeneca, Merck & Co., Accumetrics, Eli Lilly and Company/Daiichi Sankyo, sanofi-aventis/Regeneron, Bristol-Myers Squibb, Iroko Pharmaceuticals, Medscape, Eisai, Novartis, and Roche. Prof. Huber has received lecture and consultant fees from AstraZeneca, Daiichi Sankyo, Eli Lilly and Company, sanofi-aventis, Bristol-Myers Squibb, Pfizer, Iroko Pharmaceuticals, and The Medicines Company.
- Received June 7, 2013.
- Accepted June 20, 2013.
- American College of Cardiology Foundation
- Platelet Activation
- P2Y12 Receptor
- P2Y12 Receptor Antagonism
- Phenotyping: Test Systems Used for Assessment of the Effect of Antiplatelet Drugs
- Genotyping: Genes Associated With the Response Variability to Clopidogrel
- Assays for Bedside Genotyping
- Potent P2Y12 Inhibitors
- Tailored Antiplatelet Treatment