The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multice...

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Bibliographic Details
Published in:Nature medicine Vol. 27; no. 11; pp. 1954 - 1960
Main Authors: Nassif, Michael E., Windsor, Sheryl L., Borlaug, Barry A., Kitzman, Dalane W., Shah, Sanjiv J., Tang, Fengming, Khariton, Yevgeniy, Malik, Ali O., Khumri, Taiyeb, Umpierrez, Guillermo, Lamba, Sumant, Sharma, Kavita, Khan, Sadiya S., Chandra, Lokesh, Gordon, Robert A., Ryan, John J., Chaudhry, Sunit-Preet, Joseph, Susan M., Chow, Chen H., Kanwar, Manreet K., Pursley, Michael, Siraj, Elias S., Lewis, Gregory D., Clemson, Barry S., Fong, Michael, Kosiborod, Mikhail N.
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.11.2021
Nature Publishing Group
Subjects:
692/308/409
692/699/75/230
Adverse events
Aged
Antidiabetics
Benzhydryl Compounds - adverse effects
Benzhydryl Compounds - therapeutic use
Biomedical and Life Sciences
Biomedicine
Blood pressure
Cancer Research
Cardiac output
Cardiac patients
Cardiomyopathy
Care and treatment
Confidence intervals
Congestive heart failure
Dapagliflozin
Diagnosis
Double-Blind Method
Ejection fraction
Exercise - physiology
Female
Glucosides - adverse effects
Glucosides - therapeutic use
Health Status
Heart failure
Heart Failure - drug therapy
Hemoglobin
Humans
Infectious Diseases
Inhibitors
Male
Measurement
Metabolic Diseases
Middle Aged
Molecular Medicine
Neurosciences
Patients
Peptides
Placebos
Placebos - administration & dosage
Quality of life
Quality of Life - psychology
Risk factors
Sodium-glucose cotransporter
Sodium-Glucose Transporter 2 - drug effects
Sodium-Glucose Transporter 2 - metabolism
Sodium-Glucose Transporter 2 Inhibitors - adverse effects
Sodium-Glucose Transporter 2 Inhibitors - therapeutic use
Stroke Volume - drug effects
Surveys and Questionnaires
Testing
Weight reduction
United States
ISSN:1078-8956, 1546-170X, 1546-170X
Online Access:Get full text
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Summary:Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3–9.2, P  = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0–9.6, P  = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7–10.0, P  = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6–34.7, P  = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1–7.8, P  = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05–2.85, P  = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01–1.42, P  = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF. In a multicenter, randomized trial, the SGLT2 inhibitor dapagliflozin improved the health status and exercise function of patients with heart failure with preserved ejection fraction (HFpEF), a condition for which effective treatments are lacking.
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ISSN:1078-8956
1546-170X
1546-170X
DOI:10.1038/s41591-021-01536-x