• Tony Antoniou, Erin M Macdonald, Zhan Yao, Simon Hollands, Tara Gomes, Mina Tadrous, Muhammad M Mamdani, David N Juurlink, and Canadian Drug Safety and Effectiveness Research Network.
• Department of Family and Community Medicine (Antoniou), St. Michael's Hospital and University of Toronto; Li Ka Shing Knowledge Institute (Gomes) and Li Ka Shing Centre for Healthcare Analytics Research and Training (Mamdani), St. Michael's Hospital; Leslie Dan Faculty of Pharmacy (Gomes, Tadrous, Mamdani) and Department of Medicine (Juurlink), University of Toronto; Institute for Clinical Evaluative Sciences (Antoniou, Macdonald, Yao, Hollands, Gomes, Tadrous, Mamdani, Juurlink); Applied Health Research Centre (Tadrous), St. Michael's Hospital; Sunnybrook Research Institute (Juurlink), Toronto, Ont. tantoniou@smh.ca.
• CMAJ. 2017 Jan 9; 189 (1): E4-E10.

BackgroundDabigatran etexilate is a prodrug whose absorption is opposed by intestinal P-glycoprotein and which is converted by carboxylesterase to its active form, dabigatran. Unlike other statins, simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase, and might either increase the risk of hemorrhage with dabigatran etexilate or decrease its effectiveness.MethodsWe conducted 2 population-based, nested case-control studies involving Ontario residents 66 years of age and older who started dabigatran etexilate between May 1, 2012, and Mar. 31, 2014. In the first study, cases were patients with ischemic stroke; in the second, cases were patients with major hemorrhage. Each case was matched with up to 4 controls by age and sex. All cases and controls received a single statin in the 60 days preceding the index date. We determined the association between each outcome and the use of simvastatin or lovastatin, relative to other statins.ResultsAmong 45 991 patients taking dabigatran etexilate, we identified 397 cases with ischemic stroke and 1117 cases with major hemorrhage. After multivariable adjustment, use of simvastatin or lovastatin was not associated with an increased risk of stroke (adjusted odds ratio [OR] 1.33, 95% confidence interval [CI] 0.88 to 2.01). In contrast, use of simvastatin and lovastatin were associated with a higher risk of major hemorrhage (adjusted OR 1.46, 95% CI 1.17 to 1.82).InterpretationIn patients receiving dabigatran etexilate, simvastatin and lovastatin were associated with a higher risk of major hemorrhage relative to other statins. Preferential use of the other statins should be considered in these patients.© 2017 Canadian Medical Association or its licensors.

35 keywords...

hide…