{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:58:57Z","timestamp":1791302337789,"version":"4.1.0"},"reference-count":19,"publisher":"Royal College of General Practitioners","issue":"756","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Gen Pract"],"accepted":{"date-parts":[[2024,11,11]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate the association between co-prescribed DOACs and atorvastatin\/simvastatin and bleeding, cardiovascular disease, and mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and setting<\/jats:title>\n                    <jats:p>Cohort and case-crossover study using data from English general practices in the Clinical Practice Research Datalink Aurum from 1 January 2011 to 31 December 2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>A cohort design was used to estimate hazard ratios for clinically relevant pharmacological interaction safety outcomes (intracranial bleeding, gastrointestinal bleeding, and other bleeding) comparing DOACs and atorvastatin\/simvastatin with DOACs and other statins (fluvastatin, pravastatin, and rosuvastatin that are not anticipated to interact with DOACs). Effectiveness outcomes (ischaemic stroke, myocardial infarction, venous thromboembolism, cardiovascular mortality, and all-cause mortality) were also included. In addition, a case-crossover design was used to compare the odds of exposure to different drug initiation patterns in the hazard window versus the referent window within an individual.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 397 459 patients who were prescribed DOACs, 70 318 people co-prescribed atorvastatin and 38 724 co-prescribed simvastatin were selected. The cohort analysis showed no difference in risk of all outcomes comparing patients prescribed DOACs and atorvastatin\/simvastatin versus those prescribed DOACs and other statins. In the case-crossover analysis, odds ratios (ORs) for other bleeding (OR 5.06, 99% confidence interval [CI] = 3.79 to 6.76) among those initiating DOACs while taking atorvastatin and the ORs for gastrointestinal bleeding (OR 6.05, 99% CI = 4.28 to 8.54) and other bleeding (OR 6.81, 99% CI = 4.74 to 9.78) among 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study shows no evidence of interaction between DOACs and atorvastatin\/simvastatin. However, people starting a DOAC while taking atorvastatin\/simvastatin were at high risk of bleeding and mortality, likely because of temporal clinical vulnerability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3399\/bjgp.2024.0349","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T11:30:51Z","timestamp":1732793451000},"page":"e466-e473","source":"Crossref","is-referenced-by-count":6,"title":["Potential interactions between direct oral anticoagulants and atorvastatin\/simvastatin: a cohort and case-crossover study"],"prefix":"10.3399","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8618-7333","authenticated-orcid":false,"given":"Angel YS","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Warren-Gash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan","family":"Bhaskaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mence","family":"Leyrat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitava","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Smeeth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J","family":"Douglas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1987","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"2026100608352440000_75.756.e466.1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i2868"},{"key":"2026100608352440000_75.756.e466.2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.018544"},{"key":"2026100608352440000_75.756.e466.3","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-015-0936-y"},{"key":"2026100608352440000_75.756.e466.4","unstructured":"National Institute for Health and Care Excellence (NICE) British National Formulary (BNF). Simvastatin (NICE, London) https:\/\/bnf.nice.org.uk\/drugs\/simvastatin . accessed 8 May 2025."},{"key":"2026100608352440000_75.756.e466.5","unstructured":"NICE BNF. 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