Low incidence of thromboembolism with Fiix monitored warfarin compared to conventional warfarin and DOACs in atrial fibrillation patients

• Fiix-monitored warfarin has been associated with reduced thromboembolism versus PT-monitored warfarin, but has not been compared to DOACs.

• This real-world study found lowest composite thromboembolism and death rate without increased bleeding with Fiix-warfarin in AF patients.

Mixed population studies suggest that monitoring only coagulation factors II and X (Fiix) instead of conventional prothrombin time improves clinical outcomes in patients on warfarin. We hypothesized that Fiix-monitored warfarin (Fiix-warfarin) provides better real-world clinical outcomes than PT-INR monitored warfarin (PT-warfarin), apixaban, dabigatran, and rivaroxaban in non-valvular atrial fibrillation (AF) patients.

Retrospective population cohort study over a 5-year period including all long-term orally anticoagulated adult AF patients residing in the Greater Reykjavik Area. Differences in baseline characteristics were adjusted using inverse probability of treatment weighting. The principal outcomes were rates of total thromboembolism (TE), all-cause death, and major bleeding. Outcomes with Fiix-warfarin were used as reference.

6,417 patients were anticoagulated long-term for 12,914 person-years (py), i.e., Fiix-warfarin (n=1,257/py=2,514), PT-warfarin (n=1,904/py=3,998), apixaban (n=1,171/py=1,639), rivaroxaban (n=1,536/py=3,226) or dabigatran (n=549/py=1,537). PT-warfarin (1.9% per person-year (%py); hazard ratio (HR) 1.86;95% CI 1.19-2.91; P=0.007), apixaban (1.9% py;HR 1.94;1.13-3.32; P=0.02), and dabigatran (2.2% py;HR 2.19;1.18-4.06; P=0.01) had higher rates of TE compared to Fiix-warfarin (1.1% py). Similarly, rivaroxaban trended towards higher TE rates than Fiix-warfarin (1.6% py vs 1.1% py;HR 1.58;0.96-2.61; P=0.07). Rivaroxaban had significantly higher all-cause mortality rate compared to Fiix-warfarin (3.0% py vs 2.0%py;HR 1.48; 1.02-2.14;P=0.04). Major bleeding rates did not differ. Warfarin anticoagulation variability was lower with Fiix-monitoring than with PT-monitoring.

Fiix-monitored warfarin could be the most effective long-term oral anticoagulant in patients with AF. The PT-INR warfarin monitoring method should possibly be replaced.