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
Background
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.
Methods
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.
Outcomes
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).
Conclusion
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.
References
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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.
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