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DOACs Associated with Fewer Diabetic Complications than Warfarin in Atrial Fibrillation

Data from a national research database in Taiwan provides insight into the apparent reductions in risk associated with DOAC use compared to warfarin in patients with atrial fibrillation and diabetes.

New data from an analysis of patients with atrial fibrillation suggests direct oral anticoagulants (DOACs) were associated with a lower risk of complications than warfarin among patients with diabetes.

A retrospective cohort study of more than 30,000 patients, results demonstrated users of DOACs were at a 16% lower risk of developing macrovascular complications, a 21% lower risk of microvascular complications, and a 22% lower risk of mortality compared with warfarin among a population of patients with diabetes and atrial fibrillation.

“This nationwide cohort study showed that, compared with warfarin use, NOAC use was associated with lower hazards of diabetes-related complications and mortality among patients with AF and DM and without ESRD. Therefore, NOAC may be a better therapeutic choice than warfarin for decreasing these complications and mortality in patients with AF and DM requiring oral anticoagulant treatment,” wrote investigators.

As the popularity of DOACs as a treatment for atrial fibrillation has grown, so has the interest in efficacy and safety in particular subgroups. In the current study, investigators sought to explore the association between DOACs and warfarin on risk of diabetes complication in patients with atrial fibrillation and diabetes, but without chronic kidney disease. To do so, investigators designed the current analysis as a retrospective cohort study of data from Taiwan’s National Health Insurance Research Database.

Performing a search of the database from 2012-2017, investigators identified 30,219 patients for inclusion in their study. This included 19,909 DOAC users and 10,300 warfarin users. The mean age of patients was 73.8 years, 45.8% were female, and the mean follow-up duration was 2.9 years. Investigators noted propensity score-matching resulted in cohorts of 7677 patients for both the DOAC and warfarin groups.

Outcomes of interest were hazards of diabetes complications and mortality in the DOAC versus warfarin group. For the purpose of analysis, diabetes complications included macrovascular complications, microvascular compilations, and glycemic emergency. Investigators noted cause-specific Cox proportional hazards models were used to estimate hazard ratios and propensity score methods with stabilized inverse probability of treatment weighting (IPTW) were applied to balance confounders between the study groups.

Overall, the cumulative incidences of macrovascular complication, microvascular complication, glycemic emergency, and mortality were lower in DOAC users than users of warfarin after stabilized IPTW. Upon analysis, results demonstrated users of DOACs had a significant lower risk of macrovascular complications (HR, 0.84 [95% CI, 0.78-0.91]; P <.001), microvascular complications (HR, 0.79 [95% CI, 0.73-0.85]; P <.001), glycemic emergency (HR, 0.91 [95% CI, 0.83-0.99]; P=.043), and mortality (HR, 0.78 [95% CI, 0.75-0.82]; P <.001) than warfarin users in analyses with stabilized IPTW. When assessing individual complications, results suggested DOAC users had significantly lower risk of coronary artery disease, stroke, dialysis, lower-extremity amputation, and both cardiovascular and noncardiovascular mortality than warfarin users.

In further analyses stratified by age, sex, and hospital level, similar results were observed in each subgroup as in the overall analyses. In sensitivity analyses using on-treatment design, DOAC users had a lower risk of macrovascular complications (HR, 0.83 [95% CI, 0.75-0.92]; P <.001), microvascular complications (HR, 0.68 [95% CI, 0.61-0.75]; P <.001), glycemic emergency (HR, 0.81 [95% CI, 0.71-0.93]; P=.003), and mortality (HR, 0.63 [95% CI, 0.59-0.68]; P <.001). In their conclusion, investigators noted the need for further study to understand potential mechanisms behind these associations.

“Future prospective studies and randomized controlled trials are necessary to determine the causal relations,” wrote investigators.

This study, “Diabetes-Related Complications and Mortality in Patients With Atrial Fibrillation Receiving Different Oral Anticoagulants,” was published in the Annals of Internal Medicine.