27 Nov Association Between Statin Use and Ischemic Stroke or Hemorrhage in Patients Taking Dabigatran for A Fib
MedicalResearch.com Interview with:
Dr. Tony Antoniou, PhD Research Scholar
Department of Family and Community Medicine and a Scientist
Keenan Research Centre of the Li Ka Shing Knowledge Institute
St. Michael’s Hospital
Assistant Professor in the Department of Family and Community Medicine and
Leslie Dan Faculty of Pharmacy
University of Toronto, Toronto, Ontario
MedicalResearch.com: What is the background for this study?
What are the main findings?
Response: Dabigatran etexilate is an anticoagulant that is commonly used for stroke prevention in patients with atrial fibrillation. Absorption of dabigatran etexilate is opposed by intestinal P-glycoprotein, an efflux transporter. Once absorbed, dabigatran etexilate is converted to its active form by carboxylesterase enzymes. Unlike other statins, simvastatin and lovastatin can inhibit P-glycoprotein and carboxylesterase. This may result in increased absorption of dabigatran etexilate, thereby increasing the risk of bleeding. Conversely, inhibition of carboxylesterase may decrease the effectiveness of dabigatran etexilate.
MedicalResearch.com: What are the main findings?
Response: The study examined the association between statin use and subsequent hospital admission or emergency department room visits for ischemic stroke or hemorrhage in two population-based studies of older patients (> 66 years) with atrial fibrillation treated with dabigatran etexilate between May 1, 2012 and March 31, 2014. Owing to their effects on P-glycoprotein and carboxylesterase, we reasoned that simvastatin and lovastatin would be associated with higher risks of each outcome relative to other statins (pravastatin, rosuvastatin, atorvastatin, fluvastatin).
Among 45,991 patients taking dabigatran etexilate, we identified 397 cases with ischemic stroke and 1117 cases with hemorrhage. After multivariable adjustment, use of lovastatin or simvastatin was not associated with an increased risk of stroke relative to other statins (odds ratio 1.33; 95% confidence interval 0.88 to 2.01).
In contrast, use of lovastatin and simvastatin was associated with a higher risk of bleeding requiring an emergency department visit or hospital admission (odds ratio 1.46; 95% confidence interval 1.17 to 1.82) than comparator statins.
MedicalResearch.com: What should readers take away from your report?
Response: In patients treated with dabigatran etexilate, simvastatin and lovastatin were associated with a higher risk of bleeding required a visit to the emergency department or admission to hospital relative to other statins. Preferential use of other statins should be considered in these patients.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Future research examining outcomes following the combined use of P-glycoprotein inhibitors and dabigatran etexilate are needed to help inform clinical practice and safe prescribing of this drug.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
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Association between statin use and ischemic stroke or major hemorrhage in patients taking dabigatran for atrial fibrillationCMAJ cmaj.160303; published ahead of print November 21, 2016,doi:10.1503/cmaj.160303
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