Preliminary Report of the Stroke Prevention in Atrial Fibrillation Study

Abstract

Atrial fibrillation, even in the absence of rheumatic valvular disease, predisposes patients to embolic complications, but the role of antithrombotic therapy in the prevention of such complications has not been fully clarified. We therefore performed a randomized, placebo-controlled trial to evaluate warfarin and aspirin individually as prophylaxis against ischemic stroke and systemic embolism (the primary events) in such patients. Patients eligible to receive warfarin (group 1) were assigned to warfarin (open label), aspirin (325 mg per day), or placebo (aspirin and placebo were given in a doubleblind fashion). Those who were not eligible for warfarin (group 2) received either aspirin or placebo in a double-blind fashion. The placebo arm of group 1 was recently terminated, when evidence emerged that each active agent was superior to placebo. In this paper we report preliminary data on active therapy (with either warfarin or aspirin) as compared with placebo in group 1, and on aspirin as compared with placebo in groups 1 and 2 combined. By November 1989, 1244 patients had been followed for a mean of 1.13 years. The event rates were 1.6 percent per year in the 393 patients who made up the two active treatment arms (warfarin and aspirin) of group 1, and 8.3 percent per year in the 195 patients who made up the placebo arm (P less than 0.00005) (risk reduction, 81 percent; 95 percent confidence interval, 56 to 91). In all 517 patients given aspirin, the rate of primary events (3.2 percent per year) was lower than that in the 528 patients given placebo (6.3 percent per year; P = 0.014) (risk reduction, 49 percent; 95 percent confidence interval, 15 to 69). However, we were unable to show a benefit of aspirin in patients over 75 years of age. These preliminary data indicate that antithrombotic therapy with warfarin or aspirin is effective in the short term in reducing the risk of stroke and systemic embolism in patients with atrial fibrillation due to causes other than rheumatic valvular disease. The relative benefits of aspirin and warfarin remain unclear, and the trial is continuing in order to address this issue.

Atrial high-rate episodes: prevalence, stroke risk, implications for management, and clinical gaps in evidence

“…Prospective randomized studies from the late 1980s reported a dramatic and highly significant reduction in stroke in patients with AF treated with warfarin. The randomized AFASAK, 50 SPAF, 51 and BAATAF 52 studies were among the first to demonstrate that dose-adjusted warfarin prevented strokes effectively in patients with AF, confirmed in a later meta-analysis 53 …”

Long-Term Oral Anticoagulation Therapy and the Risk of Hip Fracture in Patients with Previous Hemispheric Infarction and Nonrheumatic Atrial Fibrillation

“…In those who already had sustained a fracture, especially at the hip, serum vitamin K concentrations have been found to be lower than in age-matched controls [16,17,18,19]. However, warfarin therapy has been demonstrated to reduce the risk of both primary and secondary ischemic strokes from nonrheumatic atrial fibrillation (NRAF) [20,21,22,23,24,25,26,27]. Such oral anticoagulation would seem likely to affect bone metabolism by interference with γ-carboxylated glutamyl acid protein synthesis in bone.…”

Antithrombotic Medication for Cardioembolic Stroke Prevention

“…In each of these situations, INR should be maintained between (2.0 and 3.0). In MVP patients with AF, warfarin therapy is indicated in patients aged greater than 65 years and in those with mitral regurgitation, hypertension, or a history of heart failure (INR 2.0 to 3.0) [105, 106]. Daily aspirin therapy is often recommended for patients with high-risk echocardiographic characteristics.…”