The Canadian Drug Safety and Effectiveness Research Network team identified 397 cases of ischaemic stroke and 1117 cases of major haemorrhage in 45 991 patients > 65 years with non-valvular atrial fibrillation who started dabigatran etexilate for prevention of stroke and systemic embolism. The use of simvastatin or lovastatin was not associated with an increased risk of stroke or transient ischaemic attack relative to other statins in patients taking dabigatran etexilate (OR 1.33 (95% CI 0.88 to 2.01)). In contrast, use of simvastatin and lovastatin was associated with a higher risk of major haemorrhage than comparator statins in the same patients (OR 1.46 (1.17 to 1.82)).
The authors noted that emerging evidence from in vitro studies suggests that statins administered in their lactone forms (simvastatin and lovastatin) are potent inhibitors of P-glycoprotein and carboxylesterase enzyme activity. They hypothesised that simvastatin and lovastatin might increase the absorption of dabigatran and cause an elevated risk of haemorrhage.