Stroke Prevention in Atrial Fibrillation Study. Final results. Aspirin in the prevention of progressing stroke: a randomized controlled study. Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized trial.
Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke.
                The Stroke Prevention in Atrial Fibrillation Study, a multicenter, randomized trial, compared 325 mg/day aspirin (double-blind) or warfarin with placebo for prevention of ischemic stroke and systemic embolism (primary events), and included 1,330 inpatients and outpatients with constant or intermittent atrial fibrillation. During a mean follow-up of 1.3 years, the rate of primary events in patients assigned to placebo was 6.3% per year and was reduced by 42% in those assigned to aspirin (3.6% per year; p = 0.02; 95% confidence interval, 9-63%). In the subgroup of warfarin-eligible patients (most less than 76 years old), warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67% (warfarin versus placebo, 2.3% versus 7.4% per year; p = 0.01; 95% confidence interval, 27-85%). Primary events or death were reduced 58% (p = 0.01) by warfarin and 32% (p = 0.02) by aspirin. The risk of significant bleeding was 1.5%, 1.4%, and 1.6% per year in patients assigned to warfarin, aspirin, and placebo, respectively.
                Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation. Because warfarin-eligible patients composed a subset of all aspirin-eligible patients, the magnitude of reduction in events by warfarin versus aspirin cannot be compared. Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin, and the trial is continuing to address this issue. Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke. In acute stroke, progression has a severe impact on patient outcome and no effective treatment is known. The main objective was to evaluate the efficacy of aspirin for prevention of stroke progression thereby improving outcome.
                The trial was randomized, double-blind and placebo-controlled.
                The patients were treated in stroke units of four hospitals in Sweden.
                Patients with ischaemic stroke but not complete paresis were included. No antiplatelet drugs were allowed within the last 72 h before onset. Delay until first trial dosage was maximized to 48 h. The trial was designed to detect a 20% reduction of the rate of stroke progression, which was estimated to take place in 20% of cases. Totally, 441 patients (220 aspirin, 221 placebo) completed the trial. Baseline comparisons between the groups showed no differences.
                Aspirin (325 mg) or placebo was given once daily for five consecutive days.
                Neurological assessments were carried out three times daily during the treatment period to detect progression of at least two points in the Scandinavian Stroke Supervision Scale. Patient outcome was followed up at discharge and at 3 months.
                Aspirin treatment did not significantly reduce the frequency of stroke progression. Amongst aspirin-treated patients, stroke progression occurred in 15.9% as compared with 16.7% in the placebo group, which is less frequent than expected. The relative risk was 0.95 (95% CI 0.62-1.45) in the treatment group. As regards patient outcome at discharge and after 3 months, aspirin treatment did not show any difference.
                No positive effect of aspirin, of the expected size, could be shown on the frequency of stroke progression or patient outcome. Blacks are disproportionately affected by stroke, and they are about 2 times more likely than most other individuals in the United States to die of or experience stroke.
                To determine the efficacy and safety of aspirin and ticlopidine to prevent recurrent stroke in black patients.
                Randomized, double-blind, investigator-initiated, multicenter trial of 1809 black men and women who recently had a noncardioembolic ischemic stroke and who were recruited between December 1992 and October 2001 from 62 academic and community hospitals in the United States and followed up for up to 2 years.
                A total of 902 patients received 500 mg/d of ticlopidine and 907 received 650 mg/d of aspirin.
                Recurrent stroke, myocardial infarction, or vascular death was the composite primary end point (according to intention-to-treat analysis). The secondary outcome was fatal or nonfatal stroke.
                The blinded phase of the study was halted after about 6.5 years when futility analyses revealed a less than 1% probability of ticlopidine being shown superior to aspirin in the prevention of the primary outcome end point. The primary outcome of recurrent stroke, myocardial infarction, or vascular death was reached by 133 (14.7%) of 902 patients assigned to ticlopidine and 112 (12.3%) of 907 patients assigned to aspirin (hazard ratio, 1.22; 95% confidence interval, 0.94-1.57). Kaplan-Meier curves for time to event for the primary outcome did not differ significantly (P =.12 by log-rank test). Kaplan-Meier curves for time to the secondary outcome of fatal or nonfatal stroke approached a statistically significant reduction favoring aspirin over ticlopidine (P =.08 by log-rank test). The frequency of laboratory-determined serious neutropenia was 3.4% for patients receiving ticlopdine vs 2.2% for patients receiving aspirin (P =.12) and 0.3% vs 0.2% for thrombocytopenia, respectively (P =.69). One ticlopidine-treated patient developed thrombocytopenia, which was thought to be a case of possible thrombotic thrombocytopenia purpura, and recovered after therapy with plasmapheresis.
                During a 2-year follow-up, we found no statistically significant difference between ticlopidine and aspirin in the prevention of recurrent stroke, myocardial infarction, or vascular death. However, there was a nonsignificant trend for reduction of fatal or nonfatal stroke among those in the aspirin group. Based on these data and the risk of serious adverse events with ticlopidine, we regard aspirin as a better treatment for aspirin-tolerant black patients with noncardioembolic ischemic stroke.
Aspirin appears to reduce stroke and major vascular events in patients with non-valvular AF similar to its effect in other high-risk patients (i.e. by about 25%). For primary prevention among AF patients with an average stroke rate of 4% per year, about 10 strokes would likely be prevented yearly for every 1000 AF patients given aspirin.