IMPORTANCE: Dapagliflozin has been shown to improve overall health status based on aggregate summary scores of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction enrolled in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial. A comprehensive understanding of the responsiveness of individual KCCQ items would allow clinicians to better inform patients on expected changes in daily living with treatment. OBJECTIVE: To examine the association of dapagliflozin treatment with changes in individual components of the KCCQ. DESIGN, SETTING, AND PARTICIPANTS: This is a post hoc exploratory analysis of DELIVER, a randomized double-blind placebo-controlled trial conducted at 353 centers in 20 countries from August 2018 to March 2022. KCCQ was administered at randomization and 1, 4, and 8 months. Scores of individual KCCQ components were scaled from 0 to 100. Eligibility criteria included symptomatic HF with left ventricular ejection fraction greater than 40%, elevated natriuretic peptide levels, and evidence of structural heart disease. Data were analyzed from November 2022 to February 2023. MAIN OUTCOMES AND MEASURES: Changes in the 23 individual KCCQ components at 8 months. INTERVENTIONS: Dapagliflozin, 10 mg, once daily or placebo. RESULTS: Baseline KCCQ data were available for 5795 of 6263 randomized patients (92.5%) (mean [SD] age, 71.5 [9.5] years; 3344 male [57.7%] and 2451 female [42.3%]). Dapagliflozin was associated with larger improvements in almost all KCCQ components at 8 months compared with placebo. The most significant improvements with dapagliflozin were observed in frequency of lower limb edema (difference, 3.2; 95% CI, 1.6-4.8; P < .001), sleep limitation by shortness of breath (difference, 3.0; 95% CI, 1.6-4.4; P < .001), and limitation in desired activities by shortness of breath (difference, 2.8; 95% CI, 1.3-4.3; P < .001). Similar treatment patterns were observed in longitudinal analyses integrating data from months 1, 4, and 8. Higher proportions of patients treated with dapagliflozin experienced improvements, and fewer had deteriorations across most individual components. CONCLUSIONS AND RELEVANCE: In this study of patients with HF with mildly reduced or preserved ejection fraction, dapagliflozin was associated with improvement in a broad range of individual KCCQ components, with the greatest benefits in domains related to symptom frequency and physical limitations. Potential improvements in specific symptoms and activities of daily living might be more readily recognizable and easily communicated to patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03619213.

British Heart Foundation Glasgow Cardiovascular Research Center School of Cardiovascular and Metabolic Health University of Glasgow Glasgow Scotland United Kingdom

Cardiac Intensive Care Department of Cardiovascular Diseases University Hospitals Leuven Leuven Belgium

Cardiovascular Division Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston Massachusetts

Department of Cardiology Thoraxcenter Erasmus Medical Center Rotterdam the Netherlands

Department of Cardiology University Medical Center Groningen University of Groningen Groningen the Netherlands

Department of Internal Medicine 2 Cardiology and Angiology General University Hospital 1st Medical School Charles University Prague Czech Republic

Division of Cardiology University of Texas Southwestern Medical Center Dallas

Duke University Medical Center Durham North Carolina

Haga Teaching Hospital The Hague the Netherlands

Late Stage Development Cardiovascular Renal and Metabolism BioPharmaceuticals Research and Development AstraZeneca Gothenburg Sweden

National Heart Centre Singapore and Duke National University of Singapore Singapore

Northwestern University Feinberg School of Medicine Chicago Illinois

Saint Luke's Mid America Heart Institute and University of Missouri Kansas City

Universidad Nacional de Córdoba Córdoba Argentina

University of Medicine Pharmacy Science and Technology George Emile Palade Târgu Mureș Romania

Yale School of Medicine New Haven Connecticut

Zobrazit více v PubMed

Johansson I, Joseph P, Balasubramanian K, et al. ; G-CHF Investigators . Health-related quality of life and mortality in heart failure: the global congestive heart failure study of 23 000 patients from 40 countries. Circulation. 2021;143(22):2129-2142. doi:10.1161/CIRCULATIONAHA.120.050850 PubMed DOI

Solomon SD, McMurray JJV, Claggett B, et al. ; DELIVER Trial Committees and Investigators . Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089-1098. doi:10.1056/NEJMoa2206286 PubMed DOI

Kosiborod MN, Bhatt AS, Claggett BL, et al. . Effect of dapagliflozin on health status in patients with preserved or mildly reduced ejection fraction. J Am Coll Cardiol. 2022;81(5):460-473. doi:10.1016/j.jacc.2022.11.006 PubMed DOI

Spertus JA, Jones PG, Sandhu AT, Arnold SV. Interpreting the Kansas City Cardiomyopathy Questionnaire in clinical trials and clinical care: JACC state-of-the-art review. J Am Coll Cardiol. 2020;76(20):2379-2390. doi:10.1016/j.jacc.2020.09.542 PubMed DOI

Solomon SD, de Boer RA, DeMets D, et al. . Dapagliflozin in heart failure with preserved and mildly reduced ejection fraction: rationale and design of the DELIVER trial. Eur J Heart Fail. 2021;23(7):1217-1225. doi:10.1002/ejhf.2249 PubMed DOI PMC

Green CP, Porter CB, Bresnahan DR, Spertus JA. Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure. J Am Coll Cardiol. 2000;35(5):1245-1255. doi:10.1016/S0735-1097(00)00531-3 PubMed DOI

Butler J, Filippatos G, Jamal Siddiqi T, et al. . Empagliflozin, health status, and quality of life in patients with heart failure and preserved ejection fraction: the EMPEROR-Preserved trial. Circulation. 2022;145(3):184-193. doi:10.1161/CIRCULATIONAHA.121.057812 PubMed DOI PMC

Chandra A, Vaduganathan M, Lewis EF, et al. ; PARAGON-HF Investigators . Health-related quality of life in heart failure with preserved ejection fraction: the PARAGON-HF trial. JACC Heart Fail. 2019;7(10):862-874. doi:10.1016/j.jchf.2019.05.015 PubMed DOI

Cosiano MF, Tobin R, Mentz RJ, Greene SJ. Physical functioning in heart failure with preserved ejection fraction. J Card Fail. 2021;27(9):1002-1016. doi:10.1016/j.cardfail.2021.04.013 PubMed DOI

Levine GN, Steinke EE, Bakaeen FG, et al. ; American Heart Association Council on Clinical Cardiology; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Quality of Care and Outcomes Research . Sexual activity and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2012;125(8):1058-1072. doi:10.1161/CIR.0b013e3182447787 PubMed DOI

Jaarsma T. Sexual function of patients with heart failure: facts and numbers. ESC Heart Fail. 2017;4(1):3-7. doi:10.1002/ehf2.12108 PubMed DOI PMC

Chandra A, Lewis EF, Claggett BL, et al. . Effects of sacubitril/valsartan on physical and social activity limitations in patients with heart failure: a secondary analysis of the PARADIGM-HF trial. JAMA Cardiol. 2018;3(6):498-505. doi:10.1001/jamacardio.2018.0398 PubMed DOI PMC

Zobrazit více v PubMed

ClinicalTrials.gov
NCT03619213