Poor Quality of Warfarin Treatment Increases the Risk of All Types of Intracranial Hemorrhage in Atrial Fibrillation

BACKGROUND: Intracranial hemorrhage (ICH) is a devastating complication of oral anticoagulation. The aim of this study was to describe the spectrum of ICH and to evaluate the association of warfarin control with the risk of ICH in a nationwide cohort of unselected atrial fibrillation (AF) patients. Methods and Results: The FinWAF is a retrospective registry-linkage study. Data were collected from several nationwide Finnish health-care registers and laboratory databases. The primary outcome was any ICH (traumatic or non-traumatic). The quality of warfarin therapy was assessed continuously by calculating the time in therapeutic range in a 60-day window (TTR60). Adjusted Cox proportional hazard models were used. A total of 53,953 patients were included (53% men; mean age, 73 years; mean follow-up, 2.94 years; mean TTR, 63%). In 129,684 patient-years, 1,196 patients had ICH (non-traumatic, 53.5%; traumatic, 43.6%; traumatic subdural, 38.6%); crude annual rate, 0.92%; 95% CI: 0.87-0.98). A lower TTR60 was significantly associated with higher risk of ICH (TTR60 ≤40% vs. TTR60 >80%; adjusted hazard ratio, 2.16; 95% CI: 1.83-2.54). Other variables independently associated with ICH included age >65 years, previous stroke, male sex, low hemoglobin, thrombocytopenia, elevated alanine aminotransferase, and previous bleeding other than ICH. CONCLUSIONS: Poor control of warfarin treatment was associated with elevated risk of ICH. Approximately half of the ICH were traumatic, mainly subdural.