Treatment with direct oral anticoagulants or warfarin and the risk for incident diabetes among patients with atrial fibrillation: a population‐based cohort study

Abstract

Background Diabetes mellitus is a common comorbidity of atrial fibrillation (AF), which can complicate the management of AF. The pharmacology of oral anticoagulants (OACs) have been implicated in pathogenesis of diabetes, but the relationship between different OACs and risk of diabetes remains unexamined. This study aimed to evaluate the risk of diabetes with use of different OACs in AF patients. Methods Population-based retrospective cohort study using an electronic healthcare database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with AF from 2014 through 2018 and prescribed OACs were included and followed till December 31, 2019. Inverse probability of treatment weighting based on the propensity score (PS) is used to address potential bias due to nonrandomized allocation of treatment. The risks ofdiabetes were compared between different new OAC users using propensity score-weighted cumulative incidence differences (CID). Results There were 13,688 new users of OACs (warfarin: n = 3454; apixaban: n = 3335; dabigatran: n = 4210; rivaroxaban: n = 2689). The mean age was 75.0 (SD, 11.2), and 6,550 (47.9%) were women. After a median follow-up of 0.93 years (interquartile range, 0.21–1.92 years), 698 incident diabetes cases were observed. In Cox-regression analysis, dabigatran use was significantly associated with reduced risk of diabetes when compared with warfarin use [HR 0.69 (95% CI 0.56–0.86; P < 0.001)], with statistically insignificant associations observed for use of apixaban and rivaroxaban. The corresponding adjusted CIDs at 2 years after treatment with apixaban, dabigatran, and rivaroxaban users when compared with warfarin were − 2.06% (95% CI − 4.08 to 0.16%); − 3.06% (95% CI − 4.79 to − 1.15%); and − 1.8% (− 3.62 to 0.23%). In head-to-head comparisons between women DOAC users, dabigatran was also associated with a lower risk of diabetes when compared with apixaban and rivaroxaban. Conclusions Among adults with AF receiving OACs, the use of dabigatran had the lowest risk of diabetes when compared with warfarin use.

Is the Risk of Diabetes Lower in Patients With Atrial Fibrillation Treated With Direct Oral Anticoagulant Compared to Warfarin?

“…Our study was based on two cohort studies with a total sample size of 24,434, which is the most comprehensive and latest study according to the risk of DOACs vs. warfarin in inducing new-onset diabetes in AF patients. The result in the cohort study from Cheung et al ( 15 ) proposed that only dabigatran was significantly associated with incident diabetes risk reduction, our results support that three of existing approved DOAC dabigatran, apixaban, and rivaroxaban with the function of reducing incident diabetic risk. At the same time, this effect in factor Xa inhibitors rivaroxaban and apixaban were not obvious, and our findings confirmed that all of these three drugs with the risk reduction ability.…”

“…Then 10 studies were evaluated in detail. On the basis of predefined criteria, finally, two eligible cohort studies were included in our meta-analysis ( 9 , 15 ). Exhibited in Table 1 was the baseline information of patients in the included studies.…”

“…Both included studies have reported the adjusted data of new-onset DM in AF patients treated by DOACs vs warfarin ( 9 , 15 ). The outcomes displayed in Figure 2 were able to confirm that compared with warfarin, DOACs can reduce the risk of diabetes in AF patients (HR = 0.75, 95%CI: 0.68–0.82).…”

“…Due to the different effects of warfarin and DOACs on vitamin K, the use of DOACs was considered with the potential of reducing DM risk in AF patients. Two cohort studies have been conducted to compare the risk of DM induction in AF patients treated by warfarin and DOACs ( 9 , 15 ). The study of Cheung et al included the data of 13,688 DOACs new users from the Clinical Data Analysis and Reporting System (CDARS) managed by the Hong Kong Hospital Authority (HA).…”

effect of warfarin on tail bleeding time of male wistar rats model type 2 diabetes mellitus

“…Disruption of this pathway causes the formation of fibrin threads that function to close wounds and capture blood cells to help blood clot. An increase in bleeding duration, prothrombin time (PT) and activated partial thromboplastin time (APTT) is one indication of the active mechanism of warfarin in the body (Cheung et al, 2021).…”