Drug-drug interactions compromise DOAC efficacy, aggravate bleeding risk in atrial fibrillation

In atrial fibrillation (AF) patients on direct oral anticoagulants (DOACs), drug-drug interactions (DDIs) can weaken the antithrombotic efficacy of DOACs and can worsen bleeding risk, a recent study has found.

The researchers enrolled 1,938 AF patients who were new DOAC users (median age 72 years, 61.8 percent men). Electronic health records were accessed for relevant data, including concomitant use of 45 medications that could potentially trigger DDIs with DOACs. Outcomes included hospitalization for major and gastrointestinal bleeding, ischaemic stroke (IS), and intracranial haemorrhage.

DOAC-associated IS events occurred in 29 patients, yielding an overall rate of 1.5 percent. The risk of such events was significantly elevated among those taking one (odds ratio [OR], 6.22, 95 percent confidence interval [CI], 2.65–15.67; p<0.0001) and ≥2 (OR, 12.22, 95 percent CI, 4.21–34.72; p<0.001) concomitant medications that could cause DDIs.

DDIs had a similar effect on DOAC-linked hospitalization for major bleeding, increasing its likelihood by nearly three times (OR, 2.81, 95 percent CI, 1.20–6.60; p=0.016). Such risk tended to grow with increasing number of DDIs.

Multiple logistic regression further confirmed that regardless of comorbidities, taking ≥2 drugs with potential DDIs with DOACs strongly increased the risk of both IS (OR, 18.68, 95 percent CI, 6.22–55.27; p<0.001) and hospitalization for major bleeding (OR, 5.01, 95 percent CI, 1.11–16.62; p<0.001).

“Although DOACs have comparable efficacy and enhanced safety compared to warfarin, the appropriateness and accuracy of prescribing medications are important to prevent increased risk of bleeding or reduced antithrombotic efficacy,” the researchers said.

“In the current study, we found that potential DDIs were associated with a substantially high risk for both ischemic stroke and hospitalization for major bleeding regardless of comorbidities,” they added.