Prevention of thromboembolism in atrial fibrillation. A meta-analysis of trials of anticoagulants and antiplatelet drugs

Abstract

Objective: Appropriate use of drugs to prevent thromboembolism in patients with atrial fibrillation (AF) involves comparing the patient's risk of stroke and risk of hemorrhage. This review summarizes the evidence regarding the efficacy of these medications.

Methods: We conducted a meta-analysis of randomized controlled trials of drugs used to prevent thromboembolism in adults with nonpostoperative AF. Articles were identified through the Cochrane Collaboration's CENTRAL database and MEDLINE until May 1998.

Main results: Eleven articles met criteria for inclusion in this review. Warfarin was more efficacious than placebo for primary stroke prevention (aggregate odds ratio [OR] of stroke = 0.30, 95% confidence interval [CI] 0.19, 0.48), with moderate evidence of more major bleeding (OR 1.90; 95% CI 0.89, 4.04). Aspirin was inconclusively more efficacious than placebo for stroke prevention (OR 0.56, 95% CI 0.19, 1.65), with inconclusive evidence regarding more major bleeds (OR 0.81, 95% CI 0.37, 1.77). For primary prevention, assuming a baseline risk of 45 strokes per 1,000 patient-years, warfarin could prevent 30 strokes at the expense of only 6 additional major bleeds. Aspirin could prevent 17 strokes, without increasing major hemorrhage. In direct comparison, there was evidence suggesting fewer strokes among patients on warfarin than among patients on aspirin (aggregate OR 0.64, 95% CI 0.43, 0.96), with only suggestive evidence for more major hemorrhage (OR 1.60, 95% CI 0.77,3.35). However, in younger patients, with a mean age of 65 years, the absolute reduction in stroke rate with warfarin compared with aspirin was low (5.5 per 1,000 person-years) compared with an older group (15 per 1,000 person-years).

Conclusion: In general, the evidence strongly supports warfarin for patients with AF at average or greater risk of stroke. Aspirin may prove to be useful in subgroups with a low risk of stroke, although this is not definitively supported by the evidence.

FIGURE 1

(a)Rates of stroke and hemorrhage: trials of warfarin versus placebo for patients with atrial fibrillation. ¹CAFA indicates Canadian Atrial Fibrillation Anticoagulation study: EAFT, European Atrial Fibrillation Trial; SPAF, Stroke Prevention in Atrial Fibrillation; SPINAF, Stroke Prevention in Nonrheumatic Atrial Fibrillation; BAATAF, Boston Area Anticoagulation Trial in Atrial Fibrillation. ²EAFT was a secondary prevention trial. ³Line of equivalency is the line where points would fall if there was no difference in rates between the two treatment arms. *Vertical lines represent 95% confidence intervals for the rates of stroke and hemorrhage on warfarin. **SPAF II >75 is the group over 75 years old. ***SPAFII < 75 is the group under 75 years old. Bars with diamonds (♦) indicate rates of stroke; bars with squares (▪) indicate rates of hemorrhage. (b).Rates of stroke and hemorrhage: trials of aspirin versus placebo for patients with atrial fibrillation. Abbreviations and symbols are explained in the legend to Figure 1a. (c).Rates of stroke and hemorrhage: trials of warfarin versus aspirin for patients with atrial fibrillation. Abbreviations and symbols are explained in the legend to Figure 1a. AFASAK I: data unavailable for yearly hemorrhage rate.

FIGURE 1

(a)Rates of stroke and hemorrhage: trials of warfarin versus placebo for patients with atrial fibrillation. ¹CAFA indicates Canadian Atrial Fibrillation Anticoagulation study: EAFT, European Atrial Fibrillation Trial; SPAF, Stroke Prevention in Atrial Fibrillation; SPINAF, Stroke Prevention in Nonrheumatic Atrial Fibrillation; BAATAF, Boston Area Anticoagulation Trial in Atrial Fibrillation. ²EAFT was a secondary prevention trial. ³Line of equivalency is the line where points would fall if there was no difference in rates between the two treatment arms. *Vertical lines represent 95% confidence intervals for the rates of stroke and hemorrhage on warfarin. **SPAF II >75 is the group over 75 years old. ***SPAFII < 75 is the group under 75 years old. Bars with diamonds (♦) indicate rates of stroke; bars with squares (▪) indicate rates of hemorrhage. (b).Rates of stroke and hemorrhage: trials of aspirin versus placebo for patients with atrial fibrillation. Abbreviations and symbols are explained in the legend to Figure 1a. (c).Rates of stroke and hemorrhage: trials of warfarin versus aspirin for patients with atrial fibrillation. Abbreviations and symbols are explained in the legend to Figure 1a. AFASAK I: data unavailable for yearly hemorrhage rate.

FIGURE 1

(a)Rates of stroke and hemorrhage: trials of warfarin versus placebo for patients with atrial fibrillation. ¹CAFA indicates Canadian Atrial Fibrillation Anticoagulation study: EAFT, European Atrial Fibrillation Trial; SPAF, Stroke Prevention in Atrial Fibrillation; SPINAF, Stroke Prevention in Nonrheumatic Atrial Fibrillation; BAATAF, Boston Area Anticoagulation Trial in Atrial Fibrillation. ²EAFT was a secondary prevention trial. ³Line of equivalency is the line where points would fall if there was no difference in rates between the two treatment arms. *Vertical lines represent 95% confidence intervals for the rates of stroke and hemorrhage on warfarin. **SPAF II >75 is the group over 75 years old. ***SPAFII < 75 is the group under 75 years old. Bars with diamonds (♦) indicate rates of stroke; bars with squares (▪) indicate rates of hemorrhage. (b).Rates of stroke and hemorrhage: trials of aspirin versus placebo for patients with atrial fibrillation. Abbreviations and symbols are explained in the legend to Figure 1a. (c).Rates of stroke and hemorrhage: trials of warfarin versus aspirin for patients with atrial fibrillation. Abbreviations and symbols are explained in the legend to Figure 1a. AFASAK I: data unavailable for yearly hemorrhage rate.

FIGURE 2

(a)Trials of warfarin versus placebo for patients with atrial fibrillation; odds ratios for stroke and hemorrhage. ¹CAFA indicates Canadian Atrial Fibrillation Anticoagulation study: EAFT, European Atrial Fibrillation Trial; SPAF, Stroke Prevention in Atrial Fibrillation; SPINAF, Stroke Prevention in Nonrheumatic Atrial Fibrillation; BAATAF, Boston Area Anticoagulation Trial in Atrial Fibrillation. *Horizontal bars represent 95% confidence intervals surrounding the point estimates of the odds ratios. (b).Trials of aspirin versus placebo for patients with atrial fibrillation; odds ratios for stroke and hemorrhage. Abbreviations and symbols are explained in the legend to Figure 2a. (c).Trials of warfarin versus aspirin for patients with atrial fibrillation; odds ratios for stroke and hemorrhage. Abbreviations and symbols are explained in the legend to Figure 2a.

FIGURE 2

(a)Trials of warfarin versus placebo for patients with atrial fibrillation; odds ratios for stroke and hemorrhage. ¹CAFA indicates Canadian Atrial Fibrillation Anticoagulation study: EAFT, European Atrial Fibrillation Trial; SPAF, Stroke Prevention in Atrial Fibrillation; SPINAF, Stroke Prevention in Nonrheumatic Atrial Fibrillation; BAATAF, Boston Area Anticoagulation Trial in Atrial Fibrillation. *Horizontal bars represent 95% confidence intervals surrounding the point estimates of the odds ratios. (b).Trials of aspirin versus placebo for patients with atrial fibrillation; odds ratios for stroke and hemorrhage. Abbreviations and symbols are explained in the legend to Figure 2a. (c).Trials of warfarin versus aspirin for patients with atrial fibrillation; odds ratios for stroke and hemorrhage. Abbreviations and symbols are explained in the legend to Figure 2a.

FIGURE 2

(a)Trials of warfarin versus placebo for patients with atrial fibrillation; odds ratios for stroke and hemorrhage. ¹CAFA indicates Canadian Atrial Fibrillation Anticoagulation study: EAFT, European Atrial Fibrillation Trial; SPAF, Stroke Prevention in Atrial Fibrillation; SPINAF, Stroke Prevention in Nonrheumatic Atrial Fibrillation; BAATAF, Boston Area Anticoagulation Trial in Atrial Fibrillation. *Horizontal bars represent 95% confidence intervals surrounding the point estimates of the odds ratios. (b).Trials of aspirin versus placebo for patients with atrial fibrillation; odds ratios for stroke and hemorrhage. Abbreviations and symbols are explained in the legend to Figure 2a. (c).Trials of warfarin versus aspirin for patients with atrial fibrillation; odds ratios for stroke and hemorrhage. Abbreviations and symbols are explained in the legend to Figure 2a.