Association between sodium-glucose cotransporter-2 inhibitors and incident atrial fibrillation/atrial flutter in heart failure patients with reduced ejection fraction: a meta-analysis of randomized controlled trials

Heart Fail Rev. 2023 Jul;28(4):925-936. doi: 10.1007/s10741-022-10281-3. Epub 2022 Oct 25.

Abstract

Atrial fibrillation (AF) and atrial flutter (AFL) are associated with adverse outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We investigated the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the incidence of AF and/or AFL in HFrEF patients. PubMed and ClinicalTrials.gov were systematically searched until March 2022 for randomized controlled trials (RCTs) that enrolled patients with HFrEF. A total of six RCTs with 9467 patients were included (N = 4731 in the SGLT2i arms; N = 4736 in the placebo arms). Compared to placebo, SGLT2i treatment was associated with a significant reduction in the risk of AF [relative risk (RR) 0.62, 95% confidence interval CI 0.44-0.86; P = 0.005] and AF/AFL (RR 0.64, 95% CI 0.47-0.87; P = 0.004). Subgroup analysis showed that empagliflozin use resulted in a significant reduction in the risk of AF (RR 0.55, 95% CI 0.34-0.89; P = 0.01) and AF/AFL (RR 0.50, 95% CI 0.32-0.77; P = 0.002). By contrast, dapagliflozin use was not associated with a significant reduction in the risk of AF (RR 0.69, 95% CI 0.43-1.11; P = 0.12) or AF/AFL (RR 0.82, 95% CI 0.53-1.27; P = 0.38). Additionally, a "shorter" duration (< 1.5 years) of treatment with SGLT2i remained associated with a reduction in the risk of AF (< 1.5 years; RR 0.58, 95% CI 0.36-0.91; P = 0.02) and AF/AFL (< 1.5 years; RR 0.52, 95% CI 0.34-0.80; P = 0.003). In conclusion, SGLT2i therapy was associated with a significant reduction in the risk of AF and AF/AFL in patients with HFrEF. These results reinforce the value of using SGLT2i in this setting.

Keywords: Atrial fibrillation; Atrial flutter; Heart failure; SGLT2 inhibitors.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Atrial Fibrillation* / epidemiology
  • Atrial Flutter* / complications
  • Atrial Flutter* / drug therapy
  • Atrial Flutter* / epidemiology
  • Glucose
  • Heart Failure* / complications
  • Heart Failure* / drug therapy
  • Heart Failure* / epidemiology
  • Humans
  • Randomized Controlled Trials as Topic
  • Sodium
  • Treatment Outcome
  • Ventricular Dysfunction, Left* / complications

Substances

  • Glucose
  • Sodium