Randomized Controlled Trial
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 26, 2024; 12(18): 3468-3475
Published online Jun 26, 2024. doi: 10.12998/wjcc.v12.i18.3468
Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia
Meng-Jiao Lin, Shu-Bin Zou, Bai-Xiang Zhu
Meng-Jiao Lin, Shu-Bin Zou, Bai-Xiang Zhu, Three departments of cardiovascular medicine, Harbin 242 Hospital, Harbin 150066, Heilongjiang Province, China
Co-first authors: Meng-Jiao Lin and Shu-Bin Zou.
Author contributions: Lin MJ and Zou SB proposed the concept of this study, jointly wrote the first draft; Zhu BX validated this study, contributed to data collection; Lin MJ contributed to formal analysis; Zhu BX and Lin MJ participated in the survey; Zou SB and Zhu BX contributed to the methods; Lin MJ contributed to the visualization of this study. All authors collectively guided the research, reviewed, and edited the manuscript.
Supported by General Medical Research Fund Project, No. TYYLKYJJ-2022-025.
Institutional review board statement: This study has been reviewed and approved by the Ethics Committee of Harbin 242 Hospital.
Clinical trial registration statement: This study is registered at the Clinical Registry. https://www.researchregistry.com (Reviewreg1890). Uploaded a separate file as the registration certificate.
Informed consent statement: This study has obtained the consent of patients and guardians and signed an informed consent form.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bai-Xiang Zhu, MM, Chief physician, Department of Cardiovascular, Harbin 242 Hospital, No. 3 Weijian Street, Pingfang District, Harbin 150066, Heilongjiang Province, China. farc364@163.com
Received: February 21, 2024
Revised: April 9, 2024
Accepted: April 18, 2024
Published online: June 26, 2024
Processing time: 118 Days and 0.1 Hours
Abstract
BACKGROUND

Patients with chronic heart failure (CHF) frequently develop hyperuricemia, an elevated serum uric acid level, associated with adverse outcomes. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction (HFrEF), irrespective of diabetes. However, dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear.

AIM

To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia.

METHODS

We conducted a randomized, double-blind, placebo-controlled trial in 200 patients with CHF and hyperuricemia, with HFrEF and serum uric acid levels ≥ 7 mg/dL (≥ 416 μmol/L). The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months. The primary endpoint was the change in serum uric acid level from baseline to 24 months. Secondary endpoints included changes in left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QoL) scores, as well as the incidence of cardiovascular death and hospitalization for heart failure.

RESULTS

At 24 months, dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL (71 μmol/L) compared with placebo (95%CI: -1.5 to -0.9; P < 0.001). Dapagliflozin also significantly improved LVEF by 3.5% (95%CI: 2.1-4.9; P < 0.001), NT-proBNP by 25% (95%CI: 18-32; P < 0.001), and QoL scores by 10 points (95%CI: 7-13; P < 0.001) and reduced the risk of cardiovascular death and hospitalization for heart failure by 35% (95%CI: 15–50; P = 0.002) compared with the placebo. Adverse events were similar between the two groups, except for a higher rate of genital infections in the dapagliflozin group (10% vs 2%, P = 0.01).

CONCLUSION

Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia. Therefore, dapagliflozin may be a useful therapeutic option for this high-risk population.

Keywords: Dapagliflozin, Hyperuricemia, Chronic heart failure, Sodium-glucose cotransporter-2 inhibitor, Uric acid levels, Cardiovascular mortality

Core Tip: Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor inhibitor, significantly lowers serum uric acid levels and improves clinical outcomes in patients with chronic heart failure (CHF) and hyperuricemia. This randomized trial demonstrates significant decreases in serum uric acid levels, improvements in left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide levels, and quality of life scores compared with placebo. Furthermore, dapagliflozin reduces the risk of cardiovascular death and hospitalization for heart failure. Adverse events, except for a higher incidence of genital infection in the dapagliflozin group, were similar. Thus, dapagliflozin is a promising therapeutic option for CHF patients with hyperuricemia.