Dapagliflozin benefits consistent in HF for patients with, without gout
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The benefit of dapagliflozin was consistent among adults with HF with and without gout and was associated with reduced initiation of new treatments for hyperuricemia and gout, according to a post hoc analysis of DAPA-HF and DELIVER.
“There is a consensus that the treatment of gout is suboptimal, with up to 70% of patients having recurring flares,” John J.V. McMurray, MD, professor of cardiology at the Institute of Cardiovascular and Medical Sciences at University of Glasgow in Scotland, and colleagues wrote in JAMA Cardiology. “SGLT2 inhibitors, a foundational treatment for HF, reduce uric acid levels and may therefore reduce the incidence of gout.
Data were derived from Butt JH, et al. JAMA Cardiol. 2023;doi:10.1001/jamacardio.2022.5608.
“We examined the association between gout and clinical outcomes and the effect of dapagliflozin in patients with and without gout and the introduction of new uric acid-lowering therapy and colchicine (as a proxy for gout flares) across the range of ejection fraction in two recent clinical trials in HF,” they wrote.
Gout in the HF population
McMurray and colleagues analyzed data from 11,005 participants with available gout history who participated in two phase 3 randomized clinical trials, DAPA-HF, conducted in a population with HF with reduced ejection fraction, and DELIVER, conducted in a population with HF with preserved EF. Researchers randomly assigned participants in both trials dapagliflozin (Farxiga, AstraZeneca) 10 mg once daily or placebo, plus guideline-directed medical therapy. The primary outcome was the composite of worsening HF or CV death. Median follow-up was 22 months.
Across the two studies, 10.1% of participants had a history of gout.
The prevalence of gout was 10.3% among patients with an EF of 40% or less and 10.1% among patients with an EF of more than 40%. Participants with a history of gout had a higher BMI, more comorbidities and lower estimated glomerular filtration rate and were more often treated with a loop diuretic.
The primary outcome occurred at a rate of 14.7 per 100 person-years (95% CI, 13-16.5) among participants with gout compared with 10.5 per 100 person-years (95% CI, 10.1-11) among those without, for an adjusted HR of 1.15 (95% CI, 1.01-1.31).
A history of gout was also associated with a higher risk for other outcomes examined.
Consistent results
Compared with placebo, dapagliflozin reduced the risk for the primary endpoint to the same extent in patients with (HR = 0.84; 95% CI, 0.66-1.06) and without (HR = 0.79; 95% CI, 0.71-0.87) a history of gout (P for interaction = .66). Compared with those assigned placebo, researchers observed less initiation of uric acid-lowering therapy (HR = 0.43; 95% CI, 0.34-0.53) and colchicine (HR = 0.54; 95% CI, 0.37-0.8) among participants assigned dapagliflozin.
“The reduction in the initiation of anti-gout medication with dapagliflozin most likely reflects the uric acid-lowering effect of SGLT2 inhibitors, but the mechanism for this is unknown,” the researchers wrote. “Whatever the reason, the reduction in the need for initiation of anti-gout medication represents a meaningful additional clinical benefit of dapagliflozin in patients with HF. In addition, avoiding anti-gout medication is desirable because of drug intolerance; drug interactions with HF therapies, including angiotensin-converting enzyme inhibitors and furosemide; risks of serious adverse events, such as hypersensitivity reactions; and less polypharmacy, which could improve patient adherence to lifesaving HF therapies.”
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