• Angel Ys Wong, Charlotte Warren-Gash, Krishnan Bhaskaran, Clemence Leyrat, Amitava Banerjee, Liam Smeeth, and Ian Douglas.
• London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population Health, Department of Non-communicable Disease Epidemiology, London, United Kingdom angel.wong@lshtm.ac.uk.
• Br J Gen Pract. 2024 Nov 28.

BackgroundDirect 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.AimTo investigate the association between co-prescribed DOACs and atorvastatin/simvastatin and bleeding, cardiovascular disease and mortality.Design And SettingClinical Practice Research Datalink Aurum(1/1/2011-31/12/2019).MethodWe 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.ResultsOf 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.ConclusionThis 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.Copyright © 2024, The Authors.

3 keywords...

hide…