Abstract 12458: Pharmacodynamic Effects of Dabigatran in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and Clopidogrel
Background:The use of vitamin K antagonists (VKAs) in patients on dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is associated with an increased risk of bleeding, myocardial infarction and mortality. Moreover, VKAs interfere with clopidogrel metabolism via the cytochrome P450 (CYP) system leading to increased platelet reactivity. The direct thrombin inhibitor dabigatran does not interfere with the CYP system and has a favorable safety and efficacy profile compared with VKAs. However, the pharmacodynamic (PD) effects of adjunctive dabigatran therapy in patients on DAPT is unknown.
Methods: This was a prospective, randomized, double-blind PD study conducted in patients on maintenance (>30 days) DAPT with aspirin (81mg/qd) and clopidogrel (75mg/qd). Patients (n=30) were randomized to receive either dabigatran 150mg bid or matching placebo for 7 days. PD testing was performed before and after treatment using 3 different assays: kaolin-activated thromboelastography (TEG); light transmission aggregometry (LTA); and multiple electrode aggregometry (MEA). TEG was also performed using platelet mapping software following AA and ADP stimuli; in addition to AA and ADP, LTA and MEA were also performed following stimuli with collagen and TRAP.
Results: All results were adjusted for baseline PD measures. Dabigatran significantly increased the TEG parameters indicative of the rate of coagulation initiation related to plasma factors (12.2±2.6 min vs 6.8±1.1 min; p<0.001) and time to maximum rate of thrombin generation (14.3±3 min vs 8.4±1.6 min; p<0.001), while it did not affect platelet-dependent clot strength (maximum amplitude), even with AA and ADP as agonists. No differences between groups in all PD measures, as assessed by LTA and MEA, were observed (Figure).
Conclusions: In patients on DAPT with aspirin and clopidogrel, adjunctive dabigatran therapy significantly interferes with thrombin activity without affecting platelet aggregation.
Author Disclosures: F. Franchi: None. F. Rollini: None. J. Cho: None. M. Bhatti: None. C. DeGroat: None. A. Tello-Montoliu: None. V. Duarte: None. E. Thano: None. G. Faz: None. M.M. Zenni: None. L.A. Guzman: None. R. Ajjan: None. T.A. Bass: None. D.J. Angiolillo: Research Grant; Significant; Bristol Myers Squibb, Sanofi-Aventis, Glaxo Smith Kline, Otsuka, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Evolva, and Gilead.. Honoraria; Significant; Bristol Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck, Evolva, Abbott Vascular, Bayer, and PLx Pharma. Consultant/Advisory Board; Significant; Johnson & Johnson, St. Jude, Sunovion, and CeloNova.
- © 2014 by American Heart Association, Inc.