Dapagliflozin benefits heart failure patients regardless of their gout status: JAMA

In heart failure patients, gout is a common comorbidity and is tied to adverse clinical outcomes, including HF hospitalization. Sodium-glucose cotransporter 2 inhibitors are a foundation treatment for HF that reduces uric acid levels and may therefore reduce the gout incidence. Considering this, Jawad H. Butt from the University of Glasgow in Glasgow, United Kingdom, and colleagues examined the reported gout prevalence at baseline, the relationship between gout and clinical outcomes, and the dapagliflozin's effect in patients having/not having gout and the introduction of colchicine and new uric acid–lowering therapy.

In their post hoc analysis, the researchers used data from two phase 3 RCTs (randomized clinical trials) conducted in 26 countries, DELIVER (LVEF >40%) and DAPA-HF (left ventricular ejection fraction [LVEF] ≤40%). Patients with NYHA (New York Heart Association) functional class II through IV and increased N-terminal pro–B-type natriuretic peptide (BNP) were eligible. Data analysis was done from September to December 2022.

Interventions included adding once-daily 10 mg dapagliflozin or placebo to guideline-recommended therapy. The composite of worsening heart failure or cardiovascular death was determined (primary outcome).

The study revealed the following findings:

• 10.1% of 11 005 patients had a history of gout among patients for whom gout history was available.
• The prevalence of gout was 10.1% and 10.3% in those with an LVEF, more significant than 40% and up to 40%, respectively.
• Patients with gout were more often men (80.3%) than those without (63.2%).
• The mean age was similar between groups, 69.6 years for patients with gout and 69.3 years for those without.
• Patients with a gout history had a higher body mass index, lower estimated glomerular filtration rate, and more comorbidity and were more often treated with a loop diuretic.
• The rate of primary outcome occurrence was 14.7 per 100 person-years in participants with gout compared with 10.5 per 100 person-years in those without (adjusted hazard ratio [HR], 1.15).
• A gout history was also linked with a higher risk of the other outcomes examined.
• Compared with the placebo, dapagliflozin reduced the risk of the primary endpoint to the same extent in patients with (HR, 0.84) and without a history of gout (HR, 0.79).
• In participants with and without gout, the effect of dapagliflozin use with other outcomes was shown to be consistent in participants.
• Initiation of uric acid–lowering therapy (HR, 0.43) and colchicine (HR, 0.54) was reduced by dapagliflozin compared with placebo.

"Among patients with heart failure, the dapagliflozin's beneficial effect with clinical outcomes was consistent, regardless of absence or presence of gout," the researchers wrote.

"Dapagliflozin reduced medications initiation used to treat gout flares or reduce urate level, representing a meaningful additional clinical benefit of dapagliflozin in heart failure patients," they concluded.

Reference:

Butt JH, Docherty KF, Claggett BL, et al. 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. JAMA Cardiol. Published online February 22, 2023. doi:10.1001/jamacardio.2022.5608