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Association between statin use and ischemic stroke or major hemorrhage in patients taking dabigatran for atrial fibrillation


Background — Dabigatran etexilate is a pro-drug whose absorption is opposed by intestinal P-glycoprotein and which is converted by carboxylesterases 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.

Methods — We conducted two population-based, nested case-control studies of Ontario residents 66 years of age and older who initiated dabigatran etexilate between May 1, 2012 and March 31, 2014. In the first study, cases were subjects with ischemic stroke; in the second, cases were patients with major hemorrhage. Each case was matched with up to four controls on 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.

Results — Among 45,991 patients treated with dabigatran etexilate, we identified 397 cases with ischemic stroke and 1117 cases with hemorrhage. Following multivariable adjustment, use of simvastatin or lovastatin was not associated with an increased risk of stroke (adjusted odds ratio 1.33; 95% confidence interval 0.88 to 2.01). In contrast, simvastatin and lovastatin were associated with a higher risk of hemorrhage (adjusted odds ratio 1.46; 95% confidence interval 1.17 to 1.82).

Interpretation — In patients receiving dabigatran etexilate, simvastatin and lovastatin are associated with a higher risk of hemorrhage relative to other statins. Preferential use of alternate agents may be advisable in these patients.



Antoniou T, Macdonald EM, Yao Z, Hollands S. Gomes T, Tadrous M, Mamdani MM, Juurlink DN; Canadian Drug Safety and Effectiveness Research Network. CMAJ. 2017; 184(1):E4-10. Epub 2016 Nov 21.

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