Altered Fibrin Clot Properties Predict Stroke and Bleedings in Patients with Atrial Fibrillation on Rivaroxaban

Abstract

Background and Purpose - We investigated whether clot permeability can predict clinically relevant outcomes in patients with atrial fibrillation (AF) treated with rivaroxaban. Methods - In the cohort study, we enrolled 232 consecutive patients with AF on rivaroxaban 20 mg/d (76.3%) or 15 mg/d (23.7%) for at least 3 months. Plasma clot permeability (Ks), a measure of fibrin network density, was determined 24 to 30 hours since the intake of rivaroxaban at undetectable drug's levels. Ischemic cerebrovascular events and bleedings were recorded. Results - During a median follow-up of 48 months, patients with Ks below median (6.8 cm2·10-9) had higher prevalence of stroke (5.84 versus 0.88% per year; P<0.0001) and relevant bleeding (7.06 versus 0.88% per year; P<0.0001) compared with those above median. The mortality rate was 1.53% per year and was not associated with Ks. Lower Ks predicted cerebrovascular ischemic events (hazard ratio, 6.64; 95% CI, 2.2-20.1) and relevant bleedings (hazard ratio, 7.38; 95% CI, 2.58-21.10). Minor bleeds (32.8% of patients) were observed more often in patients with Ks above median (50.9 versus 14.7%; P<0.0001). Multivariate Cox regression analysis showed that in AF patients on rivaroxaban lower Ks increased the risk of stroke (hazard ratio, 6.51; 95% CI, 2.14-19.75) and relevant bleedings (hazard ratio, 9.68; 95% CI, 3.21-29.18). Conclusions - Decreased clot permeability in AF patients can predict thromboembolic and clinically relevant bleeding events during therapy with rivaroxaban, while looser clot networks predispose to minor bleeds.