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Review
. 2025 Jun 9;17(6):e85669.
doi: 10.7759/cureus.85669. eCollection 2025 Jun.

Effect of Empagliflozin on Cardiovascular Mortality and Heart Failure Hospitalizations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Uzma Rauf  1 , Farrukh Ansar  2 , Muhammad Shazib Ali  3 , Fizza Chudhary  4 , Muhammad Haris Zafar  5 , Abdullah Azzam  2 , Muhammad Adeel Amjad  5 , Mehak Qmar Siddique  5 , Mohammad S Rauf  6 , Muhammad Bilal Ahmad  7
Affiliations
Review

Effect of Empagliflozin on Cardiovascular Mortality and Heart Failure Hospitalizations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Uzma Rauf et al. Cureus. .

Abstract

Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has demonstrated clinically meaningful benefits in patients with heart failure (HF). This systematic review and meta-analysis aimed to assess the effect of empagliflozin on cardiovascular mortality and hospitalization for heart failure (HHF) across randomized controlled trials (RCTs). A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Google Scholar, identifying five eligible RCTs. Studies were included if they evaluated empagliflozin's impact on cardiovascular mortality and HHF. A meta-analysis was performed using hazard ratios (HRs) for cardiovascular death and HHF. Data were synthesized using fixed- or random-effects models based on the degree of heterogeneity. The meta-analysis included 23,344 patients, of whom 12,849 received empagliflozin. Cardiovascular mortality was significantly reduced with empagliflozin (HR 0.86; 95% CI: 0.78-0.96). For HHF, empagliflozin reduced the risk by 30% (HR 0.70; 95% CI: 0.64-0.77) across all trials. Sensitivity analysis confirmed the robustness of these results. Empagliflozin significantly reduces cardiovascular mortality and HHF, supporting its use as a cornerstone therapy in heart failure management, especially in patients at high cardiovascular risk. These findings highlight the potential of empagliflozin as a key therapeutic intervention in heart failure care.

Keywords: cardiovascular mortality; empagliflozin; heart failure; heart failure hospitalizations; sodium-glucose co-transporter-2 (sglt2) inhibitors.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Flowchart of study selection process
Figure 2
Figure 2. Forest plot for cardiovascular death
[6,7,8,10] EMPEROR-Reduced: Empagliflozin Outcome Trial in Patients With Chronic Heart Failure and a Reduced Ejection Fraction; EMPA-REG OUTCOME: Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; EMPEROR-Preserved: Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction; EMPACT-MI: Empagliflozin in Patients With Acute Myocardial Infarction
Figure 3
Figure 3. Forest plot for hospitalization for heart failure
[6,7,8,10] EMPEROR-Reduced: Empagliflozin Outcome Trial in Patients With Chronic Heart Failure and a Reduced Ejection Fraction; EMPA-REG OUTCOME: Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; EMPEROR-Preserved: Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction; EMPACT-MI: Empagliflozin in Patients With Acute Myocardial Infarction
Figure 4
Figure 4. Forest plot for cardiovascular death (sensitivity analysis)
[6,7,8,10,11] EMPEROR-Reduced: Empagliflozin Outcome Trial in Patients With Chronic Heart Failure and a Reduced Ejection Fraction; EMPA-TROPISM: Effects of Empagliflozin on Cardiac Structure, Function, and Clinical Status in Patients With Heart Failure With Reduced Ejection Fraction Without Diabetes; EMPA-REG OUTCOME: Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; EMPEROR-Preserved: Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction; EMPACT-MI: Empagliflozin in Patients With Acute Myocardial Infarction
Figure 5
Figure 5. Forest plot of hospitalization for heart failure (sensitivity analysis)
[6,7,8,10,11] EMPEROR-Reduced: Empagliflozin Outcome Trial in Patients With Chronic Heart Failure and a Reduced Ejection Fraction; EMPA-TROPISM: Effects of Empagliflozin on Cardiac Structure, Function, and Clinical Status in Patients With Heart Failure With Reduced Ejection Fraction Without Diabetes; EMPA-REG OUTCOME: Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; EMPEROR-Preserved: Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction; EMPACT-MI: Empagliflozin in Patients With Acute Myocardial Infarction
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References

    1. Global public health burden of heart failure: an updated review. Shahim B, Kapelios CJ, Savarese G, Lund LH. Card Fail Rev. 2023;9:0. - PMC - PubMed
    1. Advancements in heart failure management: a comprehensive narrative review of emerging therapies. Sapna F, Raveena F, Chandio M, et al. Cureus. 2023;15:0. - PMC - PubMed
    1. Mortality and heart failure hospitalization among young adults with and without cardiogenic shock after acute myocardial infarction. Siddiqi HK, Defilippis EM, Biery DW, et al. J Card Fail. 2023;29:18–29. - PMC - PubMed
    1. Exploring the cardiovascular benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors: expanding horizons beyond diabetes management. Fatima A, Rasool S, Devi S, et al. Cureus. 2023;15:0. - PMC - PubMed
    1. Empagliflozin in the treatment of heart failure. Shafiq A, Hameed I, Biegus J, Fudim M, Khan MS. Future Cardiol. 2024;20:251–261. - PMC - PubMed

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