Data Analyst Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy Gainesville, United States
Background: Comorbidity of diabetes and atrial fibrillation (AF) is associated with worse cardiovascular outcomes and higher all-cause mortality. There is a lack of consensus on the clinical evidence for the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the risk of AF in type 2 diabetes (T2D) patients.
Objectives: We aimed to compare the risk of AF in SGLT2i users to dipeptidyl peptidase-4 inhibitors (DPP4i) users with T2D and determine the effect in different subgroups.
Methods: Using claims data from 15% random samples of national Medicare beneficiaries, we identified individuals with type 2 diabetes and no preexisting AF, and initiated SGLT2i or DPP4i between 01/01/2017, and 12/31/2018. The index date was defined as the date of the first filled prescription of SGLT2i or DPP4i. The outcome was the first incident AF event ever since index date. We followed individuals until outcome, death or 12/31/2018, whichever occurred first. Inverse probability treatment weighting (IPTW) was used to balance the baseline covariates, including sociodemographic, prior comorbidities and medications. Cox regression models were used for analyses.
Results: Of the 97,660 eligible individuals (age 71.2±9.8 years, 54.6% women), 1.01% (n=989) had incident AF over a median follow-up of 361 days. After IPTW, the two groups were well balanced in baseline characteristics. The crude incidence rate was 8.39 (95% confidence interval [CI]: 6.67-9.99) and 11.70 (95% CI: 10.9-12.55) event per 1000 person-years in the SGLT2i group and DPP4i group, respectively. SGLT2i were associated with a significantly lower risk of incident AF compared with DPP4i (hazard ratio [HR] 0.72; 95% CI 0.56-0.89). Subgroup analysis demonstrated that the use of SGLT2i was statistically associated with a lower risk of incident AF compared with the use of DPP4i among males (HR 0.65; 95% CI 0.47-0.89), non-Hispanic white (NHW)(HR 0.71; 95% CI 0.55-0.92) and Hispanic individuals (HR 0.36; 95% CI 0.15-0.87). Strikingly, the observed benefit of SGLT2i on AF was apparent among subgroups with existing cardiovascular (CV) conditions (HR 0.72; 95% CI 0.56-0.93) and chronic renal disease (HR 0.67; 95% CI 0.68-0.86).
Conclusions: Use of SGLT2i versus DPP4i was associated with a lower risk of AF, and the effectiveness was evident among males, NHW and Hispanic individuals, and patients with existing CV and renal conditions. Our results add valuable insight into the impact of SGLT2i on AF in real-world settings and suggest a more precise therapeutic approach to individuals with T2D.
