title: Risk and benefit of direct oral anticoagulants or PAR-1 antagonists in addition to antiplatelet therapy in patients with acute coronary syndrome.
abstract: 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 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 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.
authors.affiliation: Department of Cardiology, An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Cardiology, An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Cardiology, An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhi Jian
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Department of Cardiology, An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Shi Wei
authors.initials: SW
authors.lastname: Yang
authors.affiliation: Department of Cardiology, An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Liu
authors.affiliation: Department of Cardiology, An Zhen Hospital, Capital Medical University, Beijing, China. Electronic address: azzyj12@163.com.
authors.forename: Yu Jie
authors.initials: YJ
authors.lastname: Zhou
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000284:Administration, Oral; D000925:Anticoagulants / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors
keywords: Acute coronary syndrome; Direct Xa inhibitors; Direct thrombin inhibitors; PAR-1 antagonist