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Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Heart Failure : A Systematic Review and Meta-analysis
Xinyu Zou1, Qingyang Shi1, Per Olav Vandvik2
1Department of Endocrinology and Metabolism, Division of Guideline and Rapid Recommendation, Cochrane China Center, MAGIC China Center, Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China (X.Z., Q.S., Y.Zhou, H.T.).
Background:
Randomized controlled trials established the cardiac protection of sodium-glucose cotransporter-2 (SGLT2) inhibitors among adults with type 2 diabetes. New evidence suggests that these results could extend to people without diabetes.
Purpose:
To evaluate the effect of SGLT2 inhibitors in patients with heart failure, regardless of the presence of type 2 diabetes.
Data Sources:
PubMed, Web of Science, Cochrane Library, and Embase (OVID interface).
Study Selection:
Eligible trials randomly assigned adults with heart failure to SGLT2 inhibitors or control.
Data Extraction:
Time-to-event individual patient data were reconstructed from published Kaplan-Meier plots; time-varying risk ratios (RRs) were calculated in half-, 1-, and 2-year time frames; and anticipated absolute benefits were calculated using simple models applying relative effects to baseline risks.
Data Synthesis:
Sodium-glucose cotransporter-2 inhibitors reduce hospitalization for heart failure by 37% (95% CI, 25% to 47%) at 6 months, 32% (CI, 20% to 42%) at 1 year, and 26% (CI, 10% to 40%) at 2 years (all high certainty) and reduce cardiovascular death by 14% (CI, 1% to 25%) at 1 year (high certainty). Nevertheless, low-certainty evidence did not indicate protection against all-cause death, kidney disease progression, or kidney failure. Anticipated absolute benefits are greater for patients treated in the first year and for those with poorer prognoses, such as those newly diagnosed with heart failure in the hospital. In addition, SGLT2 inhibitors doubled the risk for genital infections (RR, 2.69 [CI, 1.61 to 4.52]; high certainty).
Limitation:
Covariates were unavailable in meta-analyses with reconstructed individual patient data.
Conclusion:
Among people with heart failure, SGLT2 inhibitors reduce hospitalizations for heart failure regardless of the presence of diabetes; absolute benefits are most pronounced in first-year treatment and vary with prognostic factors. Clinicians should note the increased risk for genital infection in patients receiving SGLT2 inhibitors.
Primary Funding Source:
1.3.5 Project for Disciplines of Excellence, West China Hospital of Sichuan University. (PROSPERO: CRD42021255544).
Insights
Sodium-glucose cotransporter-2 (SGLT2) inhibitors significantly reduce heart failure hospitalizations and cardiovascular death in patients with heart failure, irrespective of diabetes status. Benefits are greatest in the first year of treatment, but genital infections risk increases.
Area of Science:
- Cardiology
- Pharmacology
- Nephrology
Background:
- Sodium-glucose cotransporter-2 (SGLT2) inhibitors are established cardioprotective agents in type 2 diabetes.
- Emerging evidence suggests SGLT2 inhibitors may benefit patients without diabetes.
Purpose of the Study:
- To assess the efficacy of SGLT2 inhibitors in heart failure patients, with or without type 2 diabetes.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials.
- Reconstruction of individual patient data from Kaplan-Meier plots.
- Calculation of time-varying risk ratios and anticipated absolute benefits.
Main Results:
- SGLT2 inhibitors reduced heart failure hospitalizations by 37% at 6 months and 32% at 1 year (high certainty).
- Cardiovascular death was reduced by 14% at 1 year (high certainty).
- No significant effect on all-cause death or kidney disease progression was observed. Genital infection risk doubled.
Conclusions:
- SGLT2 inhibitors are effective in reducing heart failure hospitalizations and cardiovascular death in heart failure patients, regardless of diabetes.
- Absolute benefits are most significant in the first year and for high-risk patients.
- Increased risk of genital infections necessitates clinical consideration.
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