Photo courtesy of
St. Michael’s Hospital
Two commonly used statins, lovastatin and simvastatin, can increase the risk of major hemorrhage in patients receiving the anticoagulant dabigatran etexilate, according to research published in the Canadian Medical Association Journal.
“We found no difference in the risk of stroke in patients receiving dabigatran who were prescribed lovastatin or simvastatin versus other statins,” said study author Tony Antoniou, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.
“However, an increase in the risk of bleeding requiring hospital admission or emergency department visits was seen with lovastatin and simvastatin compared with the other statins.”
Dr Antoniou and his colleagues made these discoveries by conducting 2 population-based, nested case-control studies.
The studies included patients older than 65 years of age who started treatment with dabigatran etexilate between 2012 and 2014. All patients had nonvalvular atrial fibrillation and were receiving dabigatran etexilate for the prevention of stroke and systemic embolism.
In the first study, the cases were patients with ischemic stroke. In the second study, the cases were patients with major hemorrhage. Each case had up to 4 age- and sex-matched controls.
Both cases and controls received a statin. And the researchers set out to determine the association between each outcome and the use of simvastatin or lovastatin compared to other statins.
In the 45,991 patients studied, there were 397 cases of ischemic stroke and 1117 cases of major hemorrhage.
Multivariable analysis suggested that use of simvastatin or lovastatin was not associated with an increased risk of stroke or transient ischemic attack
relative to other statins. The adjusted odds ratio was 1.33.
However, the use of simvastatin and lovastatin was associated with an increased risk of major hemorrhage. The adjusted odds ratio was 1.46.
Dr Antoniou and his colleagues believe simvastatin and lovastatin increase the risk of bleeding by increasing the amount of dabigatran absorbed by the body.
The team noted that dabigatran etexilate is metabolized to dabigatran by carboxylesterase enzymes, intestinal absorption of the prodrug is opposed by P-glycoprotein, and simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase.
The researchers said the fact that the statins inhibit P-glycoprotein appears to explain the increased risk of bleeding they observed. And the fact that simvastatin and lovastatin were not associated with an increased risk of stroke suggests carboxylesterase inhibition is of little clinical relevance in this setting.
On the other hand, the researchers also noted that the number of cases receiving lovastatin and simvastatin was small. This may have influenced the team’s power to detect an association between these drugs and stroke.
Regardless, the researchers said the results of these studies suggest there is a clinically important drug interaction between dabigatran etexilate and both simvastatin and lovastatin. Therefore, other statins should be considered in patients receiving dabigatran etexilate.
