Dabigatran may interact with BP meds in patients with afib and normal kidney function

U.S. guidance currently recommends a lower dabigatran dose in those taking P-glycoprotein inhibitors only if kidney function is impaired.

Patients with normal kidney function may experience higher bleeding risk when taking verapamil or diltiazem and the direct-acting oral anticoagulant (DOAC) dabigatran, despite U.S. guidance recommending prescribing changes only in those whose kidney function is impaired.

Researchers used population-based U.S. data to perform a comparative effectiveness active comparator study among patients with nonvalvular atrial fibrillation who had received an index prescription of dabigatran, rivaroxaban, or apixaban from Oct. 19, 2010, through June 30, 2015. Patients were included only if they had no history of kidney disease and were receiving standard doses of DOACs. Those taking verapamil or diltiazem, combined P-glycoprotein and CYP3A4 inhibitors, were compared with those taking amlodipine, a dihydropyridine calcium-channel blocker, or metoprolol, a beta-blocker. The main outcomes were overall and GI major, moderate, and minor bleeding. Results of the study, which was funded by an unrestricted research grant from the PhRMA Foundation, were published April 24 by JAMA Network Open.

Overall, 1,764 patients receiving DOACs with verapamil or diltiazem were compared with 3,105 receiving amlodipine, and 1,793 patients receiving DOACs with verapamil or diltiazem were compared with 3,224 receiving metoprolol. No association with increased bleeding rates was seen for rivaroxaban and apixaban in patients taking verapamil or diltiazem versus amlodipine or metoprolol. For dabigatran, overall bleeding rate was 52% higher (hazard ratio, 1.52; 95% CI, 1.05 to 2.20) among patients also taking verapamil or diltiazem versus amlodipine and 43% higher (hazard ratio, 1.43; 95% CI, 1.02 to 2.00) among those also taking metoprolol. Risk for overall GI bleeding, minor bleeding, and minor GI bleeding was also higher for patients taking dabigatran with verapamil or diltiazem (adjusted hazard ratios, 2.16 [95% CI, 1.30 to 3.60], 1.56 [95% CI, 1.07 to 2.27], and 2.16 [95% CI, 1.29 to 3.63], respectively). In sensitivity analyses, results were consistent for dabigatran plus verapamil or diltiazem, but no significant results were seen for apixaban or rivaroxaban.

The researchers noted that their study was observational and that data on verapamil and diltiazem were combined due to the small sample size, among other limitations. They concluded that due to a drug-drug interaction, bleeding risk is increased in patients taking dabigatran with verapamil or diltiazem, even if their kidney function is normal. This effect was not seen with apixaban or rivaroxaban. “To our knowledge, this is the first real-world study to show this outcome and the findings contrast with current US prescribing recommendations,” the authors wrote. “Clinicians and patients may need to consider alternative DOAC therapy other than dabigatran during concomitant use of moderate to strong [P-glycoprotein] inhibitors regardless of kidney function or find medications that do not interact if dabigatran must be used.”