Risk and benefit of direct oral anticoagulants or PAR-1 antagonists in addition to antiplatelet therapy in patients with acute coronary syndrome

Background: The overall risk-benefit profile of direct oral anticoagulants (DOACs) or PAR-1 antagonists in addition to antiplatelet therapy for patients with acute coronary syndrome (ACS) has not been clearly established. Methods: Studies evaluating clinical outcomes of DOACs (including direct Xa inhibitors and direct thrombin inhibitors) or PAR-1 antagonists in addition to standard antiplatelet therapy in patients with recent ACS, published before Nov 2014, were screen. Eleven double blind, placebo-controlled, randomized clinical studies including 46782 patients were identified. Results: The study revealed an up to 3-fold increased risk of hemorrhagic stroke in patients receiving DOACs (OR 3.45, 95% CI 1.62 to 7.37, P = 0.001, and I-2 = 0%) or PAR-1 antagonists (OR 2.60, 95% CI 1.18 to 5.69, P = 0.02, and I-2 = 0%) in addition to antiplatelet therapy compared to those with antiplatelet therapy alone. Despite amoderate but significant reduction of composite death/MI/stroke was observed in patients with additional DOACs (OR 0.86, 95% CI 0.78 to 0.94, P = 0.002, and I-2 = 0%) or PAR-1 antagonists (OR 0.89, 95% CI 0.80 to 0.98, P = 0.02, and I-2 = 0%), due to the remarkably increased major bleeding risks, overall net clinical outcomes (death/MI/stroke/major bleeding) did not differ between patients with or without additional DOACs (OR 0.99, 95% CI 0.91 to 1.09, P = 0.88, and I-2 = 0%) or PAR-1 antagonists (OR 0.98, 95% CI 0.91 to 1.05, P = 0.55, and I-2 = 0%). Conclusions: In patients with ACS, the addition of DOACs or PAR-1 antagonists to antiplatelet therapy led to a modest but significant reduction in composite efficacy outcome at the cost of a substantial increase in hemorrhagic stroke and major bleeding events. (C) 2015 Elsevier Ltd. All rights reserved.