Sodium-glucose cotransporter 2 (SGLT2) inhibitors are ineffective for preventing atrial fibrillation in patients with heart failure, according to results published in Cardiovascular Diabetology.
Individuals with heart failure (HF) frequently have atrial fibrillation (AF) as a comorbidity, which increases risk for adverse events and complicates treatment. SGLT2 inhibitors are a promising first line treatment for HF; however, their risk reduction for AF is not yet conclusive. Researchers aimed to conduct a meta-analysis to examine conflicting results regarding the effect SGLT2 inhibitors on AF in HF patients with reduced or preserved ejection fraction (HFrEF and HFpEF).
The meta-analysis was conducted using PubMed and ClinicalTrials.gov. The researchers used key search words including SGLT2 inhibitor-related terms, “heart failure,” and “atrial fibrillation.” Studies selected included randomized controlled trials (RCTs), participants with a confirmed diagnosis of HFrEF or HFpEF, SGLT2 inhibitor and placebo use as the intervention, and data on adverse outcomes that include AF. Studies using other drug interventions besides SGLT2 inhibitors and incomplete RCTs were excluded from the study.
The primary outcome was incidence of AF, defined as AF reported as a serious adverse event or other adverse events.
A total of 10 eligible studies that compared use of SGLT2 inhibitors and placebo in a total of 16,579 patients were included in the study. Of these studies, 5 used dapagliflozin and 5 used empagliflozin. Mean age ranged from 61.3 to 73.5 years and mean follow-up time was from 12 to 26.2 weeks.
Of the patients treated with an SGLT2 inhibitor (n=8292), 348 experienced AF, while 379 AF events occurred in the participants in the placebo group (n=8287). SGLT2 inhibitor use did not significantly affect risk for AF when compared to placebo (risk ratio (RR), 0.92; 95% CI, 0.80-1.06; P =.23).
Subgroup analysis found that neither dapagliflozin or empagliflozin therapy reduced risk for AF (RR, 0.97; 95% CI, 0.73-1.28; P =.82; RR, 0.90; 95% CI, 0.76-1.06; P =.20, respectively).
Subgroup analysis was conducted using follow-up times, as they varied between studies. No significance was found in the subgroups, regardless of duration of follow-up (≤1 year: RR, 1.23; 95% CI, 0.48-3.16; P =.66; >1 year: RR, 0.85; 95% CI, 0.66-1.11; P =.24).
No significant heterogeneity was found across trials when adjusting for type of HF (HFpEF: P =.56; I2=0%; HFrEF: P =.51; I2=0%) and there was no difference in AF observed in any type of HF (HFpEF: RR, 0.99; 95% CI, 0.83-1.17; P =.87; HFrEF: RR, 0.80; 95% CI, 0.63-1.02; P =.07).
Limitations of the study include using trial studies which did not include AF as a primary endpoint, which may lead to inconsistent results. Additionally, trials could not be grouped according to comorbidities as patient-level data is not available.
“…this analysis suggests that SGLT2i [inhibitors] may not prevent the occurrence of AF in patients with HF,” the study authors wrote. “Therefore, more studies should be conducted in patients with HF to demonstrate the effects of SGLT2i on AF.”
Ouyang X, Wang J, Chen Q, Peng L, Li S, Tang X. Sodium-glucose cotransporter 2 inhibitor may not prevent atrial fibrillation in patients with heart failure: a systematic review. Cardiovasc Diabetol. Published online May 24, 2023. doi:10.1186/s12933-023-01860-1