Related Experiment Video
Updated: Oct 26, 2025
In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
SGLT2 inhibitors decrease cardiovascular death and heart failure hospitalizations in patients with heart failure: A
Rhanderson Cardoso1, Fabrissio P Graffunder2, Caique M P Ternes2,3
1Heart and Vascular Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Insights
Sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly lower mortality in heart failure (HF) patients. These drugs also reduce cardiovascular events and hospitalizations across diverse HF patient subgroups, demonstrating broad efficacy.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors are known to reduce heart failure (HF) hospitalizations and cardiovascular mortality.
- However, their effectiveness in secondary trial endpoints and specific HF patient subgroups requires further investigation.
Purpose of the Study:
- To systematically review and meta-analyze the efficacy of SGLT2 inhibitors in patients with heart failure.
- To evaluate their impact on primary endpoints (all-cause and cardiovascular mortality) and secondary endpoints across various subgroups.
Main Methods:
- A systematic review and meta-analysis of placebo-controlled, randomized trials of SGLT2 inhibitors in HF patients.
- Searched PubMed, Embase, and Cochrane databases up to January 21, 2021.
- Pooled hazard ratios (HRs) for mortality endpoints, with quality assessment performed per Cochrane recommendations.
Main Results:
- Fifteen trials involving 20,241 patients were included; 10,594 received SGLT2 inhibitors.
- SGLT2 inhibitors significantly reduced all-cause mortality (HR 0.86; 95% CI 0.79-0.94) and cardiovascular mortality (HR 0.86; 95% CI 0.78-0.96).
- The composite of cardiovascular mortality, HF hospitalizations, or urgent HF visits was significantly reduced across subgroups including sex, age, race, eGFR, NYHA class, and ejection fraction.
Conclusions:
- SGLT2 inhibitors offer significant reductions in all-cause and cardiovascular mortality in heart failure patients compared to placebo.
- The benefits extend to reducing a composite of cardiovascular mortality or HF hospitalizations/urgent visits across a wide range of patient characteristics and HF classifications.
Background:
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the composite of heart failure (HF) hospitalizations or cardiovascular mortality among patients with HF. However, the efficacy of SGLT2 inhibitors in secondary endpoints of randomized trials and in subgroups of HF patients is not well known.
Methods:
We performed a systematic review and meta-analysis of placebo-controlled, randomized trials of SGLT2 inhibitors in patients with HF. PubMed, Embase, and Cochrane databases were searched for trials published up to January 21, 2021. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Hazard ratios (HRs) with 95% CI were pooled across trials. The primary endpoints of interest were all-cause and cardiovascular mortality.
Results:
Out of 3969 database results, 15 randomized trials and 20,241 patients were included; 10,594 (52·3%) received SGLT2 inhibitors. All-cause mortality (HR 0·86; 95% CI 0·79-0·94; p = 0·0007; I2=0%) and cardiovascular mortality (HR 0·86; 95% CI 0·78-0·96; p = 0·006; I2=0%) were significantly lower in patients treated with SGLT2 inhibitors compared with placebo. The composite of cardiovascular mortality, HF hospitalizations, or urgent visits for HF was significantly reduced with SGLT2 inhibitors in all the following subgroups: male, female, age < 65, age ≥ 65, race - Black and White, estimated glomerular filtration rate (eGFR) <60, eGFR ≥60, New York Heart Association (NYHA) class II, NYHA ≥III, and HF with preserved ejection fraction.
Interpretation:
In patients with HF, SGLT2 inhibitors significantly reduce all-cause and cardiovascular mortality compared with placebo. In addition, the composite of cardiovascular mortality or HF hospitalizations/urgent visits is reduced with SGLT2 inhibitors across subgroups of sex, age, race, eGFR, HF functional class, and ejection fraction.
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