Heart failure outcomes among reduced and preserved ejection fraction patients on sodium-glucose cotransporter-2 inhibitors with different dosing patterns of diuretics: a systematic review and meta-analysis

The current review was conducted to provide information on the best dosing strategy of background loop diuretics with sodium-glucose cotransporter-2 inhibitors (SGLT2i) for heart failure and safety outcomes among reduced and preserved ejection fraction patients with comorbid conditions. The search was conducted in four databases. Study eligibility was evaluated independently, and a total of four randomized controlled trials were included in this review. Data extraction was performed using the Cochrane-modified extraction template. Statistical analyses and risk of bias assessment were conducted with RevMan version 5.4.1, while the certainty of evidence was appraised using the GRADEpro tool. The primary composite outcomes and hospitalization or urgent heart failure (HF) with SGLT2i and placebo were consistent across all the doses of loop diuretics. The primary composite outcome when loop diuretics were dosed at 40 mg [hazard ratio (HR): 0.77 and HR: 0.81] and showed high significance (p=0.0002), similar for hospitalization and urgent HF (HR: 0.73 and HR: 0.81) with (p=0.0007 and p=0.002). However, when the loop diuretics were dosed at 40 mg, they showed highly significant (p