Effects of SGLT2i are not modified by gout history in patients with HF

Association of Dapagliflozin Use With Clinical Outcomes and the Introduction of Uric Acid-Lowering Therapy and Colchicine in Patients With Heart Failure With and Without Gout: A Patient-Level Pooled Meta-analysis of DAPA-HF and DELIVER

Literature - Butt JH, Docherty KF, Claggett BL, et al. - JAMA Cardiol. 2023 Apr 1;8(4):386-393. doi: 10.1001/jamacardio.2022.5608.

Introduction and methods


Gout is common in patients with HF and associated with adverse clinical outcomes [1-5]. SGLT2i therapy reduces uric acid levels, and therefore may reduce the risk of gout [6-8].

Aim of the study

The authors investigated the association between gout and clinical outcomes in patients with HF. Moreover, the effect of dapagliflozin in patients with HF with and without gout were examined, as well as the effect of dapagliflozin on the introduction of new uric-acid lowering therapy and colchicine in these patients.


This was a pooled post hoc analysis of 2 phase 3 clinical trials with dapagliflozin which included 11,005 patients with HF. Data of the DAPA-HF and DELIVER trials, which were randomized, double-blind, clinical trials with patients with symptomatic HF and elevated natriuretic peptide levels, were used. Patients with LVEF of ≤40% were enrolled in DAPA-HF, and patients with LVEF of >40% in DELIVER. Patients received dapagliflozin (10 mg) once daily or placebo. A total of 117 patients (10.1%) had a history of gout at baseline (10.3% with LVEF ≤40% and 10.2% with LVEF >40%). History of gout was investigator-reported.


The primary outcome was the composite of worsening HF or CV death.

Main results

Gout and clinical outcomes

  • The incidence of the primary outcome occurred at a rate of 14.7 per 100 person-years (95% CI: 13.0 to 16.5) in patients with gout compared with 10.5 per 100 person-years (95%CI: 10.1 to 11.0) in patients without gout (adjusted HR: 1.15; 95%CI: 1.01 to 1.31).

Effects of dapagliflozin

  • Dapagliflozin reduced the risk of worsening HF or CV death compared to placebo in patients with gout (HR: 0.84; 95%CI: 0.66 to 1.06) and without gout (HR: 0.79; 95%CI: 0.71 to 0.87) (P for interaction=0.66).
  • Dapagliflozin use was associated with a lower initiation of uric-acid lowering therapies compared to placebo (HR: 0.43; 95%CI: 0.34 to 0.53). This association was not modified by gout history (P for interaction=0.73) or LVEF (P for interaction=0.65). Similar results were found for the initiation of colchicine (HR: 0.54; 95%CI: 0.37 to 0.80; P for interaction for gout history=0.76; P for interaction for LVEF=0.06).


This pooled analysis demonstrated that dapagliflozin has beneficial effects on CV outcomes in patients with HF irrespective of gout status. Moreover, dapagliflozin use was associated with a lower initiation of new uric-acid lowering therapies or colchicine.


1. Loosen SH, Roderburg C, Curth O, et al. The spectrum of comorbidities at the initial diagnosis of heart failure: a case control study. Sci Rep. 2022;12(1):2670.

2. Ergatoudes C, Schaufelberger M, Andersson B, et al. Non-cardiac comorbidities and mortality in patients with heart failure with reduced vs. preserved ejection fraction: a study using the Swedish Heart Failure Registry. Clin Res Cardiol. 2019;108(9):1025-1033.

3. Carnicelli AP, Clare R, Chiswell K, et al. Comparison of characteristics and outcomes of patients with heart failure with preserved ejection fraction with versus without hyperuricemia or gout. Am J Cardiol. 2020;127:64-72.

4. Thanassoulis G, Brophy JM, Richard H, Pilote L. Gout, allopurinol use, and heart failure outcomes. Arch Intern Med. 2010;170(15):1358-1364.

5. DeMizio D, Wu G, Wei Y, et al. Gout increases length of stay in patients hospitalized for heart failure exacerbation. Ther Adv Musculoskelet Dis. 2022;14:1759720X221102853.

6. Doehner W, Anker SD, Butler J, et al. Uric acid and sodium-glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction: the EMPEROR-reduced trial. Eur Heart J. 2022;43(36):3435-3446.

7. McDowell K, Welsh P, Docherty KF, et al. Dapagliflozin reduces uric acid concentration, an independent predictor of adverse outcomes in DAPA-HF. Eur J Heart Fail. 2022;24(6):1066-1076.

8. Hu X, Yang Y, Hu X, et al. Effects of sodium-glucose cotransporter 2 inhibitors on serum uric acid in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis. Diabetes Obes Metab. 2022;24(2):228-238.

Find this article online at JAMA Cardiol.

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