Causes of late mortality with dual antiplatelet therapy after coronary stents

Eur Heart J. 2016 Jan 21;37(4):378-85. doi: 10.1093/eurheartj/ehv614. Epub 2015 Nov 18.

Abstract

Aims: 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.

Methods and 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).

Conclusion: 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.

Trial registration: clinicaltrials.gov Identifier: NCT00977938.

Keywords: Cancer; Dual antiplatelet therapy; Mortality; Thienopyridine.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Cause of Death
  • Drug Therapy, Combination
  • Drug-Eluting Stents*
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality
  • Neoplasms / complications
  • Neoplasms / mortality
  • Percutaneous Coronary Intervention / methods
  • Percutaneous Coronary Intervention / mortality
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Pyridines
  • thienopyridine
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00977938