Abstract
Background:Direct oral anticoagulants (DOACs) are commonly co-prescribed with statins. Although biologically plausible, whether there is a drug interaction between DOACs and atorvastatin/simvastatin is unclear. Aim:To investigate the association between co-prescribed DOACs and atorvastatin/simvastatin and bleeding, cardiovascular disease and mortality. Design and Setting:Clinical Practice Research Datalink Aurum(1/1/2011-31/12/2019). Method: We used a cohort design to estimate hazard ratios for clinically relevant pharmacological interaction safety outcomes (intracranial bleeding, gastrointestinal bleeding, other bleeding) comparing DOACs+atorvastatin/simvastatin with DOACs+other statins (fluvastatin, pravastatin and rosuvastatin which are not anticipated to interact with DOACs). Effectiveness outcomes (ischaemic stroke, myocardial infarction, venous thromboembolism, cardiovascular mortality, and all-cause mortality) were also included. A case-crossover design comparing odds of exposure to different drug initiation patterns in hazard window versus referent window within an individual was also conducted. Results:Of 397,459 DOAC users, we selected 70,318 people co-prescribed atorvastatin, and 38,724 co-prescribed simvastatin. The cohort analysis showed no difference in risk of all outcomes comparing DOACs+atorvastatin/simvastatin versus DOACs+other statins. In case-crossover analysis, ORs for other bleeding (OR:4.04; 99%CI:3.07–5.31) amongst those initiating DOACs while taking atorvastatin, and the ORs for gastrointestinal bleeding (OR:5.16; 99%CI:3.66–7.28) and other bleeding (OR:5.12; 99%CI:3.61–7.26) amongst those initiating DOACs while taking simvastatin were greater than those initiating DOAC monotherapy. Similar patterns were also observed for cardiovascular mortality and all-cause mortality. Conclusion:This study shows no evidence of interaction between DOACs and atorvastatin/simvastatin. However, people starting a DOAC whilst taking atorvastatin/simvastatin, were at high risk of bleeding and mortality, likely due to temporal clinical vulnerability.
- Received June 18, 2024.
- Accepted November 11, 2024.
- Copyright © 2024, The Authors
