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  • Efficacy and safety of sodium‑glucose cotransporter 2 inhibitors initiation in patients with acute heart failure, with and without type 2 diabetes: a systematic review and meta‑analysis

Efficacy and safety of sodium‑glucose cotransporter 2 inhibitors initiation in patients with acute heart failure, with and without type 2 diabetes: a systematic review and meta‑analysis

What was known?

Regardless of diabetes status, patients with chronic heart failure (HF) across a varied spectrum of left ventricular ejection fraction have shown positive results in improving cardiovascular outcomes with sodium-glucose cotransporter 2 (SGLT2) inhibitors.

Objective(s):

This systematic review and meta-analysis aim to provide a reliable estimate of the efficacy and safety of SGLT2 inhibitors initiated in patients hospitalised due to acute heart failure (AHF).

What this study adds:

This study provides valuable data regarding initiation of SGLT2 inhibitors among patients hospitalised with AHF to inform treatment decisions for optimal management of patients in the outpatient setting.

Clinical implications:

These data suggest that initiation of SGLT2 inhibitors in patients who were hospitalised due to AHF, before or within 3 days of discharge could reduce the risk of rehospitalisation and improve patient-reported outcomes, with no increase in the risk of adverse effects.

Study design:

PubMed/Medline, Embase, and Cochrane library were searched using the following terms: (“sglt2" and "acute heart failure") and (“sglt2" and "worsening heart failure") up to November 15th, 2021 for randomised control trials (RCTs) comparing the efficacy and safety of initiating an SGLT2 inhibitor compared with placebo in patients with AHF. Key cardiovascular and diabetes scientific meetings in 2021 were also searched for unpublished studies.

Primary endpoints:

  • Prespecified efficacy outcomes were all-cause mortality, rehospitalisation for HF, and improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) scale score

Secondary endpoints:

  • Prespecified safety outcomes were acute kidney injury (AKI), hypotension, and hypoglycaemia

Inclusion criteria:

  • RCTs
  • Trials with an active arm in which an SGLT2 inhibitor was started in patients hospitalised due to AHF
  • Trials with selected prespecified efficacy and safety outcomes
    • Efficacy outcomes were selected based on previous studies showing decrease in the risk of all-cause mortality and hospitalisation for HF and improvement in KCCQ scale score in patients on SGLT2 inhibitors without AHF
    • Safety outcomes were selected based on tolerability concerns related to AKI, hypotension, and hypoglycaemia in patients with AHF initiating SGLT2 inhibitors  

Notable exclusion criteria:

No other restrictions were applied

Findings:

  • A total of 1831 patients within 3 RCTs were included
  • All selected studies were considered to have a low risk of bias
  • The initiation of SGLT2 inhibitors in patients hospitalised for AHF resulted in:
  • Reduced risk of rehospitalisation for HF (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.42–0.65; I2= 0%; certainty: high)
    • Improved Kansas City Cardiomyopathy Questionnaire scores (mean difference, 4.12; 95% CI, 0.1.89–6.53; I2= 0%; certainty: high)
    • No significant effects in all-cause mortality (OR, 0.70; 95% CI, 0.46–1.08; I2= 18%; certainty: high).
    • No increase in the acute kidney injury (OR, 0.76; 95% CI, 0.50–1.16; I2= 10%; certainty: high), hypotension (OR, 1.17; 95% CI, 0.80–1.71; I2= 0%; certainty: high), or hypoglycaemia (OR, 1.51; 95% CI, 0.86–2.65; I2= 0%; certainty: high)

Interpretation:

In patients hospitalised for AHF, initiation of SGLT2 inhibitors during hospitalisation or within 3 days of discharge reduces the odds of rehospitalisation for HF by 48% and significantly improves patient-reported outcomes with no rise in the risk of adverse effects such as AKI, hypotension, or hypoglycaemia. Failure to do so, not only could have negative effects on AHF patients’ quality of life and risk of rehospitalisation, but also could increase the hospitalisation rates in patients with AHF as observed in recent years.

Limitations:

  • Published summary data rather than individual patient level data were used
  • Included trials used different versions of KCCQ (KCCQ-total vs. KCCQ-12)
  • Included trials had different follow-up periods ranging from 60 days to > 9 months
  • Two of the trials initiated treatment with SGLT2 prior to discharge in all patients, however another trial allowed inclusion of patients receiving the first dose of SGLT2 inhibitor ≤ 3 days after discharge

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