Eight-year follow-up of the Clopidogrel After Surgery for Coronary Artery Disease (CASCADE) trial

J Thorac Cardiovasc Surg. 2018 Jan;155(1):212-222.e2. doi: 10.1016/j.jtcvs.2017.06.039. Epub 2017 Jun 24.

Abstract

Objective: In this 8 years' follow-up study, we evaluated the long-term outcomes of the addition of clopidogrel to aspirin during the first year after coronary artery bypass grafting, versus aspirin plus placebo, with respect to survival, major adverse cardiac, or major cerebrovascular events, including revascularization, functional status, graft patency, and native coronary artery disease progression.

Methods: In the initial Clopidogrel After Surgery for Coronary Artery Disease trial, 113 patients were randomized to receive either daily clopidogrel (n = 56) or placebo (n = 57), in addition to aspirin, in a double-blind fashion for 1 year after coronary artery bypass grafting. All patients were re-evaluated to collect long-term clinical data. Surviving patients with a glomerular filtration rate > 30 mL/min were asked to undergo a coronary computed tomography angiogram to evaluate the late saphenous vein graft patency and native coronary artery disease progression.

Results: At a median follow-up of 7.6 years, survival rate was 85.5% ± 3.8% (P = .23 between the 2 groups). A trend toward enhanced freedom from all-cause death or major adverse cardiac or cerebrovascular events, including revascularization, was observed in the aspirin-clopidogrel group (P = .11). No difference in functional status or freedom from angina was observed between the 2 groups (P > .57). The long-term patency of saphenous vein graft was 89.11% in the aspirin-clopidogrel group versus 91.23% in the aspirin-placebo group (P = .79). A lower incidence of moderate to severe native disease progression was observed in the aspirin-clopidogrel group versus the aspirin-placebo group (7 out of 122 vs 13 out of 78 coronary segments that showed progression, respectively [odds ratio, 0.3 ± 0.2; 95% confidence interval, 0.1-0.8; P = .02]).

Conclusions: At 8 years' follow-up, the addition of clopidogrel to aspirin during the first year after coronary artery bypass grafting exhibited a lower incidence of moderate to severe progression of native coronary artery disease and a trend toward higher freedom from major adverse cardiac or cerebrovascular events, including revascularization, or death in the aspirin-clopidogrel group.

Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT00228423.

Keywords: antiplatelet drugs; coronary artery bypass graft; coronary disease.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aspirin / administration & dosage
  • Aspirin / adverse effects
  • Clopidogrel* / administration & dosage
  • Clopidogrel* / adverse effects
  • Computed Tomography Angiography / methods
  • Coronary Angiography / methods
  • Coronary Artery Bypass / adverse effects*
  • Coronary Artery Bypass / methods
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / surgery*
  • Coronary Restenosis / etiology
  • Coronary Restenosis / prevention & control*
  • Double-Blind Method
  • Drug Therapy, Combination / methods*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Outcome and Process Assessment, Health Care
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Survival Analysis
  • Vascular Patency / drug effects

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00228423