Mortality predictors and effects of antithrombotic therapies in atrial fibrillation: insights from ACTIVE-W

To assess the risk of death after the occurrence of different types of non-fatal events in patients with atrial fibrillation (AF). Antithrombotic therapies in AF have primarily focused on stroke prevention and bleeding. However, strokes and bleeds differ in severity, and the level of severity may differently impact mortality. We analysed the risk of subsequent mortality after the occurrence of non-fatal vascular and bleeding events in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE)-W trial. In the 3371 patients randomized to vitamin K antagonists and the 3335 patients randomized to clopidogrel plus aspirin in ACTIVE-W, the hazard ratio (HR) and 95% confidence intervals (95% CIs) for subsequent death associated with the occurrence of non-fatal stroke was 5.58 (95% CI 3.84-8.10, P < 0.0001). Both ischaemic (HR 5.29, 95% CI 3.53-7.93, P < 0.0001) and haemorrhagic strokes (HR 7.38, 95% CI 2.74-19.9, P < 0.0001) increased mortality, but transient ischaemic attacks did not. Disabling strokes (Rankin's score >= 3) increased mortality (HR 9.54; 95% CI 6.42-14.2, P < 0.0001), but non-disabling strokes did not. Severe bleeding increased mortality (HR 3.35, 95% CI 2.12-5.27, P < 0.0001), but major bleeding that was not severe according to the study definitions did not. Non-fatal strokes increased mortality in ACTIVE-W, but non-disabling strokes did not. Among major bleeding events, only those also classified as severe increased mortality. Future research should emphasize the prevention of disabling strokes and severe bleeds and place less emphasis on non-disabling stroke or major bleeds that are not severe.