title: Causes of late mortality with dual antiplatelet therapy after coronary stents.
abstract: OBJECTIVE
  In the dual antiplatelet therapy (DAPT) study, continued thienopyridine beyond 12 months after drug-eluting stent placement was associated with increased mortality compared with placebo. We sought to evaluate factors related to mortality in randomized patients receiving either drug-eluting or bare metal stents in the DAPT study.
  
  
  RESULTS
  Patients were enrolled after coronary stenting, given thienopyridine and aspirin for 12 months, randomly assigned to continued thienopyridine or placebo for an additional 18 months (while taking aspirin), and subsequently treated with aspirin alone for another 3 months. A blinded independent adjudication committee evaluated deaths. Among 11 648 randomized patients, rates of all-cause mortality rates were 1.9 vs. 1.5% (continued thienopyridine vs. placebo, P = 0.07), cardiovascular mortality, 1.0 vs. 1.0% (P = 0.97), and non-cardiovascular mortality, 0.9 vs. 0.5% (P = 0.01) over the randomized period (Months 12-30). Rates of fatal bleeding were 0.2 vs. 0.1% (P = 0.81), and deaths related to any prior bleeding were 0.3 vs. 0.2% (P = 0.36), Months 12-33). Cancer incidence did not differ (2.0 vs. 1.6%, P = 0.12). Cancer-related deaths occurred in 0.6 vs. 0.3% (P = 0.02) and were rarely related to bleeding (0.1 vs. 0, P = 0.25). After excluding those occurring in patients with cancer diagnosed before enrolment, rates were 0.4 vs. 0.3% (P = 0.16).
  
  
  CONCLUSIONS
  Bleeding accounted for a minority of deaths among patients treated with continued thienopyridine. Cancer-related death in association with thienopyridine therapy was mainly not related to bleeding and may be a chance finding. Caution is warranted when considering extended thienopyridine in patients with advanced cancer.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00977938.
authors.affiliation: Harvard Clinical Research Institute, Boston, USA Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA Harvard Medical School , Boston, USA lmauri1@partners.org.
authors.forename: Laura
authors.initials: L
authors.lastname: Mauri
authors.affiliation: Harvard Clinical Research Institute, Boston, USA Harvard Medical School , Boston, USA Massachusetts General Hospital, Boston, USA.
authors.forename: Sammy
authors.initials: S
authors.lastname: Elmariah
authors.affiliation: Harvard Clinical Research Institute, Boston, USA Harvard Medical School , Boston, USA Massachusetts General Hospital, Boston, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Yeh
authors.affiliation: Harvard Clinical Research Institute, Boston, USA Harvard Medical School , Boston, USA Beth Israel Deaconess Medical Center, Boston, USA.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Cutlip
authors.affiliation: Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique - Hôpitaux de Paris, Paris, France National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, UK.
authors.forename: P Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Bern University Hospital, Bern, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Windecker
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA Harvard Medical School , Boston, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wiviott
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, MO, USA University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Cohen
authors.affiliation: Harvard Clinical Research Institute, Boston, USA Boston University School of Public Health, Boston, USA Université Paris-Diderot, INSERM U-1148, Hôpital Bichat, Paris, France.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.affiliation: Harvard Clinical Research Institute, Boston, USA Boston University School of Public Health, Boston, USA.
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA Harvard Medical School , Boston, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: The Christ Hospital Heart and Vascular Center, The Lindner Center for Research and Education, Cincinnati, OH, USA.
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Kereiakes
mesh_terms: D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D002423:Cause of Death; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D009369:Neoplasms / Q000150:complications / Q000401:mortality; D062645:Percutaneous Coronary Intervention / Q000379:methods / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C446540:thienopyridine; D001241:Aspirin
keywords: Cancer; Dual antiplatelet therapy; Mortality; Thienopyridine