Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study

J Am Coll Cardiol. 2004 Oct 19;44(8):1557-66. doi: 10.1016/j.jacc.2004.05.084.

Abstract

Objectives: This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis.

Background: Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated.

Methods: We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism.

Results: Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy.

Conclusions: The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients.

Publication types

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

MeSH terms

  • Acenocoumarol / adverse effects
  • Acenocoumarol / therapeutic use*
  • Aged
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / mortality
  • Cause of Death
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Embolism / mortality
  • Embolism / prevention & control
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced
  • Hemorrhage / mortality
  • Humans
  • International Normalized Ratio
  • Intracranial Embolism / mortality
  • Intracranial Embolism / prevention & control
  • Male
  • Middle Aged
  • Mitral Valve Stenosis / drug therapy*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Proportional Hazards Models
  • Salicylates / adverse effects
  • Salicylates / therapeutic use*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Salicylates
  • triflusal
  • Acenocoumarol