1. SGLT-2 inhibitors reduced time to first hospitalization and cardiovascular death among patients with preserved, mildly reduced, and reduced ejection fractions.

2. The number needed to treat (NNT) to prevent a first hospitalization was 28 in patients receiving SGLT-2 inhibitors.

Evidence Rating Level: 1 (Excellent)

Study Rundown: SGLT-2 inhibitors have been used to manage heart failure patients with reduced ejection fractions. However, their efficacy in patients with mixed or preserved ejection fraction remains unclear. The current study includes patients from two large-scale trials, DELIVER and EMPEROR-Preserved, with mildly reduced or preserved ejection fraction. This meta-analysis aimed to assess the safety and efficacy of SGLT-2 inhibitors on heart failure-related hospitalization and cardiovascular mortality. Primary outcome was the time to admission or cardiovascular death, while key secondary outcomes included worsening heart failure event and all-cause mortality. According to study results, SGLT-2 inhibitors decreased the rate of cardiovascular mortality and heart failure-related hospitalization. The benefits seen with SGLT-2 inhibitors was demonstrated across various levels of ejection fractions. A major strength of this study was that it aggregated data from five well-conducted randomized controlled trials, thus adding to its validity.

Click to read the study in The Lancet

Relevant Reading: Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure

In-depth [meta-analysis]: This study comprised of patients from 5 large-scale trials (DAPA-HF, DELIVER, EMPEROR-Reduced, EMPEROR-Preserved, and SOLOIST-WHF) conducted between 2017 and 2021. Each of the included trials compared an SGLT-2 inhibitor (dapagliflozin, empagliflozin, and sotagliflozin) to placebo control. Included were patients with reduced (HFrEF) and preserved (HFpEF) ejection fraction, and those admitted for worsening heart failure. The primary composite outcome (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.73-0.87) was significantly reduced in patients receiving SGLT-2 inhibitors. The benefits of SGLT-2 inhibitors were further demonstrated with improvements in first admission for heart failure (HR 0.74, 95% CI 0.67-0.83) and cardiovascular death (HR 0.88, 95% CI 0.77-1.00) among patients with HFpEF (n=12251). This was also the case for patients in all 5 trials, regardless of ejection fraction: hospitalization for health failure (HR 0.72, 95% CI 0.67-0.78), cardiovascular death (HR 0.87, 95% CI 0.79-0.95), and all-cause mortality (HR 0.92, 95% CI 0.86-0.99). Treatment with SGLT-2 inhibitors reduced the risk of first hospitalization for heart failure with a NNT of 28. Overall, findings from this study recommend the routine use of SGLT-2 inhibitors in patients with heart failure with both reduced and preserved ejection fraction.

Image: PD

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