title: Ischaemic and bleeding complications with new, compared to standard, ADP-antagonist regimens in acute coronary syndromes: a meta-analysis of randomized trials.
abstract: BACKGROUND
  Platelets play a pivotal role in the pathogenesis of acute coronary syndromes (ACS) and their inhibition remains a mainstay therapy in this setting. We aimed to perform a meta-analysis of randomized trials to evaluate the benefits of new oral antiplatelet regimens to block platelet ADP-receptors compared to standard-dose clopidogrel (300 mg loading dose followed by 75 mg/daily).
  
  
  METHODS
  We obtained results from all randomized trials enrolling patients with ACS. Primary endpoint was mortality. Secondary endpoints were myocardial infarction and definite in-stent thrombosis. Safety endpoint was the risk of major bleeding complications. We prespecified subanalyses according to new antiplatelet drugs (prasugrel/ticagrelor), high-dose clopidogrel (600 mg) and patients undergoing percutaneous coronary intervention.
  
  
  RESULTS
  A total of seven randomized trials were finally included in the meta-analysis (n = 58 591). We observed a significant reduction in mortality (2.9% vs. 3.4%, OR = 0.87, 95% CI 0.79-0.95, P = 0.002), recurrent myocardial infarction (4.2% vs. 5.2%, OR = 0.80, 95% CI 0.74-0.87, P < 0.0001), definite in-stent thrombosis (0.9% vs. 1.7%, OR = 0.52, 95% CI 0.43-0.63, P < 0.0001). The benefits in mortality and reinfarction were driven by the treatment with prasugrel or ticagrelor, without a significant difference in terms of major bleeding complications as compared to standard-dose clopidogrel (5% vs. 4.7%, OR = 1.06 95% CI 0.96-1.17, P = 0.25).
  
  
  CONCLUSIONS
  This meta-analysis showed that new oral antiplatelet regimens are associated with a significant reduction in mortality, reinfarction and in-stent thrombosis in ACS patients without an overall increase of major bleeding when treated with new antiplatelet drugs.
authors.affiliation: Maggiore della Carità Hospital, Università del Piemonte Orientale, Novara, Italy.
authors.forename: E P
authors.initials: EP
authors.lastname: Navarese
authors.forename: M
authors.initials: M
authors.lastname: Verdoia
authors.forename: A
authors.initials: A
authors.lastname: Schaffer
authors.forename: P
authors.initials: P
authors.lastname: Suriano
authors.forename: M
authors.initials: M
authors.lastname: Kozinski
authors.forename: F
authors.initials: F
authors.lastname: Castriota
authors.forename: S
authors.initials: S
authors.lastname: De Servi
authors.forename: J
authors.initials: J
authors.lastname: Kubica
authors.forename: G
authors.initials: G
authors.lastname: De Luca
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives; D000284:Administration, Oral; D000077144:Clopidogrel; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D007511:Ischemia / Q000139:chemically induced*; D010879:Piperazines / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D000068799:Prasugrel Hydrochloride; D016032:Randomized Controlled Trials as Topic; D013876:Thiophenes / Q000009:adverse effects; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine