title: Efficacy and safety of prolonged dual antiplatelet therapy: a meta-analysis of 15 randomized trials enrolling 85 265 patients.
abstract: OBJECTIVE
  The optimal duration of dual antiplatelet therapy (DAPT) in patients with ischaemic cardiovascular (CV) disease is still debated. Previous meta-analyses reported conflicting results about prolonged DAPT on mortality and major CV events. Aim of this study was to assess the effects of prolonged vs. no/short-term DAPT on myocardial infarction (MI), stroke, bleeding, and mortality.
  
  
  RESULTS
  Trial inclusion criteria were: randomization to prolonged duration vs. no/short DAPT; reporting of at least one outcome among overall and CV death, MI, stroke, major non-fatal, fatal, and intracranial bleeding. Fifteen randomized studies including 85 265 patients were included. Prolonged DAPT, compared with no or short DAPT, significantly reduced MI (RR: 0.785, 95% CI: 0.729-0.845, P < 0.001) and stroke (RR: 0.851, 95% CI: 0.754-0.959, P = 0.008), but had no effect on overall (RR: 0.989, 95% CI: 0.921-1.061, P = 0.751) or CV (RR: 0.951, 95% CI: 0.872-1.037, P = 0.258) mortality. Prolonged DAPT significantly increased major non-fatal (RR: 1.690, CI: 1.322-2.159, P < 0.001), but not intracranial or fatal bleeding (RR: 1.236, CI: 0.899-1.698, P = 0.192, RR: 1.069, CI: 0.760-1.503, P = 0.703; respectively). The effects of DAPT were similar to those reported in the overall analysis in patients with stable CV disease, whereas in those with unstable CV disease only the significant reduction of stroke was not confirmed. Dual antiplatelet therapy prolonged beyond 1 year significantly reduced MI but not stroke, all-cause, or CV death. It significantly increased the risk of major non-fatal bleeding, with no difference in intracranial and fatal bleeding.
  
  
  CONCLUSIONS
  Prolonged DAPT significantly reduced ischaemic CV events but not mortality. Even if a significant increase of major non-fatal bleeding was detected, no increased risks of intracranial and fatal bleeding were observed.
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Via S. Pansini 5, 80131 Naples, Italy Department of Medicine, Unit of Cardiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Savarese
authors.affiliation: Division of Cardiology, Ospedale Manzoni, Lecco, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Savonitto
authors.affiliation: Department of Medicine, Unit of Cardiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lund
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Via S. Pansini 5, 80131 Naples, Italy IRCCS SDN, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Paolillo
authors.affiliation: Istituto Diagnostico Varelli, Naples, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Marciano
authors.affiliation: Villa dei Fiori, Acerra, Naples, Italy Mount Sinai Medical School, New York, USA.
authors.forename: Santo
authors.initials: S
authors.lastname: Dellegrottaglie
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Parente
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.affiliation: University Heart Center, Zurich, Switzerland.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Luscher
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Via S. Pansini 5, 80131 Naples, Italy fpperron@unina.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Perrone-Filardi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors
keywords: Dual antiplatelet therapy; acute coronary syndrome; meta-analysis; randomized clinical trials; stable coronary artery disease