Wong, Angel YS;
Warren-Gash, Charlotte;
Bhaskaran, Krishnan;
Leyrat, Clemence;
Banerjee, Amitava;
Smeeth, Liam;
Douglas, Ian;
(2024)
Potential interactions between direct oral anticoagulants and atorvastatin/simvastatin: cohort and case-crossover study.
British Journal of General Practice
, Article BJGP.2024.0349. 10.3399/BJGP.2024.0349.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Potential interactions between direct oral anticoagulants and atorvastatin/simvastatin: cohort and case-crossover study |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3399/BJGP.2024.0349 |
| Publisher version: | https://doi.org/10.3399/bjgp.2024.0349 |
| Language: | English |
| Additional information: | Copyright © 2024 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License (http://creativecommons.org/licenses/by/4.0/). Published by British Journal of General Practice. For editorial process and policies, see: https://bjgp.org/authors/bjgp-editorial-process-and-policies. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10207069 |
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