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

- The value of triple antithrombotic therapy in ACS was evaluated.
- Triple therapy had an up to 3-fold increased risk of intracranial hemorrhage.
- Triple therapy did not improve net clinical outcome.

BackgroundThe 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.MethodsStudies 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.ResultsThe 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 I2 = 0%) or PAR-1 antagonists (OR 2.60, 95% CI 1.18 to 5.69, P = 0.02, and I2 = 0%) in addition to antiplatelet therapy compared to those with antiplatelet therapy alone. Despite a moderate 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 I2 = 0%) or PAR-1 antagonists (OR 0.89, 95% CI 0.80 to 0.98, P = 0.02, and I2 = 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 I2 = 0%) or PAR-1 antagonists (OR 0.98, 95% CI 0.91 to 1.05, P = 0.55, and I2 = 0%).ConclusionsIn 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.