Canadian atrial fibrillation anticoaguiation (CAFA) study

Abstract

The Canadian Atrial Fibrillation Anticoagulation Study was a randomized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage. As a result of the publication of two other "positive" studies of similar design and objective, this study was stopped early before completion of its planned recruitment of 630 patients. There were 187 patients randomized to warfarin and 191 to placebo. Permanent discontinuation of study medication occurred in 26% of warfarin-treated and 23% of placebo-treated patients. The target range of the international normalized ratio was 2 to 3. For the warfarin-treated patients, the international normalized ratio was in the target range 43.7% of the study days, above it 16.6% of the study days and below it 39.6% of the study days. Fatal or major bleeding occurred at annual rates of 2.5% in warfarin-treated and 0.5% in placebo-treated patients. Minor bleeding occurred in 16% of patients receiving warfarin and 9% receiving placebo. The primary outcome event cluster was nonlacunar stroke, noncentral nervous systemic embolism and fatal or intracranial hemorrhage. Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication. The annual rates of the primary outcome event cluster were 3.5% in warfarin-treated and 5.2% in placebo-treated patients, with a relative risk reduction of 37% (95% confidence limits, -63.5%, 75.5%, p = 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of Cardioembolic Stroke

“…Multiple studies have identified these risk factors for stroke in patients with AF. These include the Atrial Fibrillation Investigators (AFI), the Boston Area Anticoagulation Trial of Atrial Fibrillation Investigators (BAATAF) [40], Stroke Prevention in Atrial Fibrillation (SPAF) [41,42], Stroke Prevention in Nonrheumatic Atrial Fibrillation (SPINAF), Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study (AFA-SAK) [43], and Canadian Atrial Fibrillation Anticoagulation (CAFA) study [44]. Several stroke risk stratification schemes have been proposed [45,46], and one scheme has not been definitely proven superior to another scheme or 100% predictive of ischemic stroke risk [45,46].…”

The decision to anticoagulate: Assessing whether benefits outweigh the risks for patients with atrial fibrillation

“…10,11 Randomized controlled trials have consistently demonstrated that long-term anticoagulant prophylaxis reduces stroke risk in patients with nonvalvular atrial fibrillation (NVAF). [12][13][14][15][16][17] A formal meta-analysis of five primary prevention trials (Atrial , 50-79%) reduction in risk for stroke with warfarin therapy versus placebo over an observational period of nearly 3,700 patient years. 18 The efficacy of warfarin was consistent across all studies and patient subgroups.…”

The cost-effectiveness of different management strategies for patients on chronic warfarin therapy

“…For example, if frequency of testing for patient self-testing increases to 57 times a year (base 52), then moving from anticoagulation testing to patient self-testing would no longer be cost saving when all costs are included, although the cost would still be a modest $608 per event avoided or $3,758 per QALY. Converseley, overall model results were not sensitive to the discount rate used (range, 0%-10%), or assumptions regarding the percentage of patients discontinuing therapy after a permanent disability (range, 20%-80%), the wage rate used to value patient and caregiver time (range, $11-$17 per hour), and the annual number of tests that would occur during routine visits (range, [4][5][6][7][8][9][10][11][12][13][14]. A multi-way sensitivity analysis, in which all assumptions within the model were allowed to vary within their specified ranges, confirmed overall results.…”

“…Using the average of these values, we assumed patients receiving usual care spend 33% of their time (range, 15%-50%) below and 17% of their time (range, 10%-25%) above therapeutic range. For anticoagulation clinic testing, we assumed that patients spend 26% percent of their time (range, 8%-40%) below and 9% of their time (range, 1%-17%) above therapeutic range to reflect the averages of those reported by a number of large anticoagulation clinical trials, [13][14][15][16][17][18][19][20][21] as well as data from four observational studies. 3,6,22,23 For patient self-testing, patients were assumed to spend 6% of their time (range, 5%-15%) below and 5% of their time (range, 1%-7%) above therapeutic range, reflecting the average of those reported by White et al, 23 Anderson et al, 9 Ansell et al, 6 and Hasenkam et al 7 Associated with these estimates of time spent below, in, and above therapeutic range are first and subsequent thromboembolic and hemorrhagic event rates (Table 1).…”