6- versus 24-month dual antiplatelet therapy after implantation of drug-eluting stents in patients nonresistant to aspirin: the randomized, multicenter ITALIC trial

J Am Coll Cardiol. 2015 Mar 3;65(8):777-786. doi: 10.1016/j.jacc.2014.11.008. Epub 2014 Nov 16.

Abstract

Background: The currently recommended duration of dual antiplatelet therapy (DAPT) in drug-eluting stent (DES) recipients is 12 months to reduce the risk of late stent thrombosis, particularly in those with acute coronary syndrome (ACS).

Objectives: This study hypothesized that antiplatelet treatment with DAPT for 6 months may be noninferior to 24-month DAPT in aspirin-sensitive patients.

Methods: A multicenter, randomized study assigned patients undergoing implantation of everolimus-eluting stents with confirmed nonresistance to aspirin to receive 6- or 24-month DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-stenting.

Results: A total of 2,031 patients were enrolled in 70 European and Middle Eastern centers. The trial was prematurely terminated due to recruitment problems, leaving 941 patients randomized to 24-month DAPT and 953 to 6-month DAPT. The 2 treatment groups had similar baseline and procedural characteristics. There was no significant difference in the primary endpoint (24-month: 1.5% vs. 6-month: 1.6%; p = 0.85). Noninferiority was demonstrated for 6- versus 24-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: -1.04% to 1.26%; p for noninferiority = 0.0002). There were no significant differences in stent thrombosis or bleeding complications. In the 792 (44%) high-risk patients with ACS, primary and secondary endpoints did not significantly differ (hazard ratio: 1.7 [95% confidence interval: 0.519 to 6.057; p = 0.361]).

Conclusions: Rates of bleeding and thrombotic events were not significantly different according to 6- versus 24-month DAPT after PCI with new-generation DES in good aspirin responders. (Is There A LIfe for DES After Discontinuation of Clopidogrel [ITALICplus]; NCT01476020).

Keywords: double antiplatelet duration; percutaneous coronary angioplasty.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin* / administration & dosage
  • Aspirin* / adverse effects
  • Clopidogrel
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / physiopathology
  • Coronary Artery Disease / therapy*
  • Coronary Restenosis* / diagnosis
  • Coronary Restenosis* / etiology
  • Coronary Restenosis* / prevention & control
  • Coronary Vessels / pathology
  • Coronary Vessels / surgery
  • Drug-Eluting Stents / adverse effects*
  • Early Termination of Clinical Trials
  • Europe
  • Everolimus
  • Female
  • Hemorrhage* / etiology
  • Hemorrhage* / prevention & control
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Middle East
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / methods
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Postoperative Complications / diagnosis
  • Postoperative Complications / prevention & control
  • Sirolimus / analogs & derivatives
  • Sirolimus / therapeutic use
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Platelet Aggregation Inhibitors
  • Everolimus
  • Clopidogrel
  • Ticlopidine
  • Aspirin
  • Sirolimus

Associated data

  • ClinicalTrials.gov/NCT01476020