title: Safety and efficacy of protease-activated receptor-1 antagonists in patients with coronary artery disease: a meta-analysis of randomized clinical trials.
abstract: BACKGROUND
  Thrombin receptor antagonists blocking protease-activated receptor-1 (PAR-1) on platelets represent a new class of oral antiplatelet agents for patients with atherothrombotic disease manifestations.
  
  
  OBJECTIVE
  We investigated the safety and efficacy of PAR-1 antagonists in patients with coronary artery disease (CAD).
  
  
  METHODS
  Randomized, placebo-controlled trials of the PAR-1 antagonists atopaxar or vorapaxar in CAD patients were identified. The primary safety endpoint was the composite of Thrombolysis In Myocardial Infarction (TIMI) clinically significant bleeding. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke.
  
  
  RESULTS
  A total of 41 647 patients from eight trials were included. PAR-1 antagonists were associated with higher risks of TIMI clinically significant (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.39-1.57, P < 0.001), major (OR 1.46, 95% CI 1.28-1.67, P < 0.001) and minor (OR 1.67, 95% CI 1.40-2.00, P < 0.001) bleeding than placebo in the fixed-effects model. PAR-1 antagonists reduced the composite of death, MI or stroke as compared with placebo (OR 0.87, 95% CI 0.81-0.92, P < 0.001), driven by a lower risk of MI (OR 0.85, 95% CI 0.78-0.92, P < 0.001). Conversely, PAR-1 antagonists and placebo did not differ in terms of risk of death (OR 0.99, 95% CI 0.90-1.09, P = 0.81) or stroke (OR 0.96, 95% CI 0.84-1.10, P = 0.59).
  
  
  CONCLUSIONS
  PAR-1 antagonists decrease ischemic events in patients with CAD as compared with placebo, mainly driven by a reduction in MI, at the cost of an increased risk of clinically significant bleeding.
authors: Ferrarotto Hospital, Catania, Italy.
authors: D
authors: D
authors: Capodanno
authors: D L
authors: DL
authors: Bhatt
authors: S
authors: S
authors: Goto
authors: M L
authors: ML
authors: O'Donoghue
authors: D J
authors: DJ
authors: Moliterno
authors: C
authors: C
authors: Tamburino
authors: D J
authors: DJ
authors: Angiolillo
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D019317:Evidence-Based Medicine; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007097:Imines / Q000009:adverse effects / Q000627:therapeutic use*; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D044463:Receptor, PAR-1 / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: C540445:E 5555; D007097:Imines; D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D044463:Receptor, PAR-1; C530299:vorapaxar