Extended Duration Dual Antiplatelet Therapy After Coronary Stenting Among Patients With Peripheral Arterial Disease: A Subanalysis of the Dual Antiplatelet Therapy Study

JACC Cardiovasc Interv. 2017 May 8;10(9):942-954. doi: 10.1016/j.jcin.2017.02.013.

Abstract

Objectives: This study sought to determine whether patients with peripheral arterial disease (PAD) experience different reductions in ischemic event and increases in bleeding events with extended duration dual antiplatelet therapy versus those without PAD.

Background: Patients with PAD have increased ischemic and bleeding risks after coronary stenting.

Methods: The DAPT (Dual Antiplatelet Therapy) study randomized 11,648 patients free from ischemic and bleeding events 12 months after coronary stenting to continued thienopyridine plus aspirin therapy for an additional 18 months versus aspirin therapy alone. The effects of continued thienopyridine on myocardial infarction (MI) or stent thrombosis, major adverse cardiovascular and cerebrovascular events (death, MI, or stroke) and bleeding (GUSTO [Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries] moderate or severe) were assessed among those with versus without PAD.

Results: Among 11,648 randomized patients, 649 (5.57%) had PAD. Between 12 and 30 months, randomized patients with PAD had higher rates of MI/stent thrombosis (6.03% vs. 2.92%; p < 0.001), major adverse cardiovascular and cerebrovascular events (11.65% vs. 4.62%; p < 0.001), and bleeding (4.86% vs. 1.74%; p < 0.001). Continued thienopyridine versus placebo was associated with consistent treatment effects for MI/stent thrombosis (with PAD, HR: 0.63; 95% CI: 0.32 to 1.22; without PAD, HR: 0.53; 95% CI: 0.42, 0.66; interaction p = 0.631), major adverse cardiovascular and cerebrovascular events (with PAD, HR: 1.06; 95% CI: 0.67 to 1.67; without PAD, HR: 0.70; 95% CI: 0.59 to 0.84; interaction p = 0.103), and bleeding (with PAD, HR, 1.82; 95% CI: 0.87 to 3.83; without PAD, HR: 1.66; 95% CI: 1.23 to 2.24; interaction p = 0.811).

Conclusions: Among patients undergoing coronary stenting, those with PAD have more ischemic and bleeding events versus those without PAD. Extended duration dual antiplatelet therapy is associated with consistent ischemic benefit and bleeding harm among patients with and without PAD.

Keywords: bleeding; dual antiplatelet therapy; ischemia; peripheral arterial disease.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Clopidogrel
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / therapy*
  • Coronary Thrombosis / etiology
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Percutaneous Coronary Intervention / adverse effects
  • Percutaneous Coronary Intervention / instrumentation*
  • Percutaneous Coronary Intervention / mortality
  • Peripheral Arterial Disease / complications*
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / mortality
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Prasugrel Hydrochloride / administration & dosage*
  • Prasugrel Hydrochloride / adverse effects
  • Proportional Hazards Models
  • Risk Factors
  • Stents*
  • Stroke / etiology
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine
  • Aspirin