Vol. 53 | No. 1 | January-June 2025 Back

Open Access

Sodium-Glucose Cotransporter-2 Inhibitors and Health-Related Quality of Life Outcomes in All Types of Heart Failure: A Systematic Review and Meta-Analysis

Billy Joseph David, Bea Christine Joyce Buot, Reynald Evan Tugade, Ferdinand R. Gerodias Jr.
May 2025 DOI 10.69944/pjc.69d1d8143d

Abstract

Introduction: Exercise intolerance in patients with heart failure (HF) leads to a lower quality of life. An increasing number of studies suggest that early initiation of guided-directed medical therapy (GDMT) leads to better outcomes. Sodium-glucose cotransporter-2 (SGLT-2) inhibitor is one of the cornerstones in HF treatment, but its effectiveness in improving quality of life remains uncertain.

Methods: A comprehensive search of randomized controlled trials (RCT) was conducted. Outcome measures for cardiovascular death and HF symptoms using the Kansas City Cardiomyopathy Questionnaire - Total Symptom Score (KCCQ-TSS) in the early phase of treatment and at 8 months were analyzed using the Review Manager V5.4. The KCCQ-TSS ranges from 0 to 100, with higher scores indicating fewer symptoms and physical limitations associated with HF. The treatment effect was shown as a win ratio, in which a value greater than 1 indicates superiority.

Results: Five RCTs were included in the meta-analysis. There was improvement in HF symptoms based on the KCCQ-TSS (HR 3.39 [95%CI: 2.95-3.89]I2 = 68%, p<0.00001) with substantial heterogeneity. The major source of heterogeneity identified was the interval when the KCCQ-TSS was performed, hence a subgroup analysis that specifically monitored patients during the eighth month of treatment was done, which showed improvement in HF symptoms (HR 3.16 [95%CI: 2.98-3.36)I2 = 8%, p<0.00001) in SGLT-2 inhibitors compared to placebo.

Conclusion: The meta-analysis showed that initiation of SGLT-2 inhibitors resulted in improvement of HF symptoms which may lead to improvement of patients’ quality of life. Therefore, SGLT-2 inhibitors in all types of HF are effective in promoting better quality of life.

Keywords: Sodium-glucose cotransporter-2 inhibitor, heart failure, quality of life

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Tables and Figures

Tables

Table 1. Review of Studies on SGLT-2 Inhibitors

Study

Design

Number of Participants

Type of Heart Failure

Intervention

Control

Follow-up period

Outcomes

DAPA-HF

201911

RCT

4,744

HFrEF

Dapagliflozin 10 mg once daily

Placebo

18.2 months

1)Worsening HF

2)CV mortality

3)KCCQ symptoms

4)Worsening renal function

DELIVER

20229

RCT

6,263

 

HFmrEF, HFpEF

Dapagliflozin 10 mg once daily

Placebo

2.3 years

1)Worsening HF

2)CV mortality

3)KCCQ symptoms

EMPEROR

PRESERVED

202110

RCT

5,988

HFpEF

Empagliflozin 10 mg once daily

Placebo

26.2 months

1)Hospitalization

2)CV mortality

3)KCCQ symptoms

4)Change in eGFR

EMPEROR

REDUCED

20205

RCT

3,730

HFrEF

Empagliflozin 10 mg once daily

Placebo

16 months

1)Hospitalization

2)CV mortality

3)KCCQ symptoms

4)Decline in eGFR

EMPULSE

202213

RCT

530

HFrEF

HFmrEF

HFpEF in AHF

Empagliflozin 10 mg once daily

Placebo

3 months

1)CV death

2)KCCQ symptoms

3)Time to death

HF, heart failure; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; KCCQ, Kansas City Cardiomyopathy Questionnaire; CV, cardiovascular; eGFR, estimated glomerular filtration rate

 

 

Figures

 

Figure 1. PRISMA Flow Diagram

 

 

Note: The figure shows the review authors’ judgments about each risk-of-bias item in the column for each included study in the rows. A green dot with a plus symbol indicates presence of a bias item in a corresponding study. A red dot with a minus symbol indicates absence of a bias item in a corresponding study.

Figure 2. Cochrane Risk of Bias Assessment

 

 

Figure 3. KCCQ-TSS Forest Plot Comparison of SGLT-2 Inhibitor Versus Placebo.

 

Figure 4. KCCQ-TSS Forest Plot Comparison of SGLT-2 Inhibitor Versus Placebo in the 8th Month.

 

Figure 5. Cardiovascular Death Forest Plot Comparison of SGLT-2 Inhibitor Versus Placebo

 

Figure 6. Funnel Plot Comparison of SGLT-2 Inhibitor Versus Placebo on KCCQ-TSS

 

Figure 7. Funnel Plot Comparison of SGLT-2 Inhibitor Versus Placebo on Cardiovascular Death

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