Association Between Statins Use and Major Bleeding in Patients Using Direct Oral Anticoagulants for Atrial Fibrillation

BACKGROUND: Direct oral anticoagulants (DOAC) were developed as an alternative to vitamin K antagonists in the treatment of NVAF. Statins are frequently prescribed drugs for the prevention of atherosclerotic cardiovascular disease. A potential interaction between DOACs and statins has been described, suggesting that their concomitant use may increase the risk of major bleeding (MB). PURPOSE: To estimate the risk of MB associated with concomitant use of DOACs and statins to assess potential safety issues. METHODS: A case-control study nested in a cohort of new users of DOACs was performed in BIFAP. Cases were defined as MB events and matched to four controls by risk-set sampling. Treatment episodes were built to define the participants' exposure according to their use at index date as current, recent, past, or no use. Exposure was also assessed in relation to its continuity and duration. Variables were created based on the concomitant use of DOACs and statins to study the interaction, using conditional logistic regression to estimate the risk of MB. RESULTS: aOR (95% CI) for current use of DOAC or statin use were 1.35 (0.96-1.9) and 0.72 (0.59-0.88). aOR for their concomitant use was 1.31 (0.83-2.07) compared to nonuse of either of them. DOAC continuous use (1.27; 0.8-2.03) and long-term (1.11; 0.67-1.81) treatment was associated with smaller risks than noncontinuous (1.40; 0.85-2.32) and short-term treatment (1.43; 0.94-2.45). Analyses by individual DOACs and statins showed similar results except for edoxaban, which had low numbers. CONCLUSIONS: There was no evidence to suggest an interaction between DOACs and statins and the risk of MB. Regular use of DOACs is important to minimize their impact on MB onset.