Clot Lysis Time Predicts Stroke During Anticoagulant Therapy in Patients with Atrial Fibrillation

Formation of dense fibrin clots has been reported in both atrial fibrillation (AF) and ischemic stroke. We have previously demonstrated that such clot properties can predict thromboembolism and major bleeding in AF patients treated with vitamin K antagonists (VKAs). In this longitudinal cohort study, we evaluated whether impaired fibrinolysis is associated with clinical outcomes in AF.

In 236 patients with AF receiving VKAs, we measured ex vivo plasma clot lysis time (CLT), a measure of global fibrinolysis along, with von Willebrand factor antigen (vWF), plasminogen activator inhibitor 1 antigen (PAI-1), and other fibrinolysis modulators. The primary outcome were ischemic cerebrovascular events. Secondary end points were death and major bleeding.

During a median follow-up time of 4.3 (interquartile range 3.7-4.8) years, annual rates of death, ischemic cerebrovascular events, and major bleeding were 1.48%, 2.96%, and 3.45%, respectively. Patients with CLT in the fourth quartile (> 115 min) had 8-fold higher stroke or transient ischemic attack (TIA) rates compared with the other patients (8.67% vs 1.1%; P < 0.0001). CLT correlated with PAI-1 and vWF (r = 0.59; P < 0.0001 for both). In the multivariate Cox regression analysis adjusted for potential confounders, the independent predictors of stroke or TIA were CLT > 115 minutes (hazard ratio [HR] 7.67, 95% confidence interval [CI] 2.78-21.17; P < 0.0001), PAI-1 (HR 1.16, 95% 1.05-1.28; P = 0.003), and CHA₂DS₂-VASc score ≥3 (HR 5.18, 95% 1.76-15.29; P = 0.003). CLT was not associated with death or major and minor bleeding events.

Impaired fibrinolysis may predict thromboembolic events in AF patients receiving VKA.