Curriculum in CardiologyOral antiplatelet therapy for atherothrombotic disease: Current evidence and new directions
Section snippets
Aspirin
Trials with aspirin have demonstrated a reduction of ischemic events in patients with ACS6 and those scheduled for percutaneous coronary intervention (PCI).6, 16 A meta-analysis of 16 randomized trials (43,000 patient-years) that evaluated aspirin versus no treatment for secondary prevention demonstrated a significant, approximately 20% reduction in major coronary events in patients receiving aspirin (risk ratio 0.87, 95% CI 0.78-0.98).17 The risk of major extracranial bleeding, including
Clopidogrel
The CAPRIE trial evaluated the efficacy of clopidogrel monotherapy versus aspirin monotherapy in secondary prevention of atherothrombotic disease. Monotherapy with clopidogrel demonstrated modestly greater efficacy versus aspirin monotherapy (Table I7, 8, 9, 10, 18, 19, 20, 21, 22, 23, 24), whereas the bleeding rates were comparable among the groups (Table II7, 8, 9, 10, 19, 20, 21, 22, 23, 24).7 Treatment with aspirin alone led to a higher rate of intracranial hemorrhage versus clopidogrel
Prasugrel
Prasugrel (Figure 1, Figure 4) is an oral, irreversible thienopyridine P2Y12 antagonist (Table III10, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36) with a faster onset of action time and greater potency versus clopidogrel.37 In TRITON-TIMI 38, which enrolled 13,608 patients with ACS undergoing PCI, the combination of prasugrel plus aspirin significantly reduced the risk of the composite end point of death from CV causes, nonfatal MI, or nonfatal stroke versus the combination of clopidogrel plus
Ticagrelor
Ticagrelor (Figure 1, Figure 4) is a nonthienopyridine, direct-acting, and selective inhibitor of the P2Y12 ADP receptor with rapid onset of action (2 hours to peak platelet inhibition) (Table III).43 Importantly, ticagrelor binding to the P2Y12 ADP receptor is reversible (Figure 4), with partial recovery of platelet aggregation within 12 hours after discontinuation of treatment.37 This feature of ticagrelor may be advantageous because rapid reversal of platelet inhibition after discontinuation
Conclusion
Single antiplatelet therapy with aspirin and dual antiplatelet therapy with aspirin and a P2Y12 antagonist (clopidogrel or prasugrel) have documented efficacy in the prevention and treatment of atherothrombotic disease. Dual antiplatelet therapy has been associated with improved efficacy over single-agent therapy, but bleeding rates are increased, and there remains an unmet need in continuing high ischemic event rates. Ticagrelor has been shown to reduce mortality versus clopidogrel, although
Acknowledgements
The author would like to thank Charlene Nell, team support administrator, Green Lane Cardiovascular Research Unit, for excellent secretarial assistance.
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Cited by (0)
Dr White has received research grants from Sanofi-Aventis, Eli Lilly, Medicines Company, NIH, Pfizer, Roche, Johnson & Johnson, Schering Plough, Merck Sharp & Dohme, AstraZeneca, GlaxoSmithKline, Daiichi-Sankyo Pharma Development, and Bristol-Myers Squibb. He has also received a consultancy fee from Regado Biosciences.