Dapagliflozin Use Reduces Risk in Heart Failure, Need for Uric Acid Lowering in Gout Patients

John McMurray, MD, PhD
Courtesy: University of Glasgow

A patient-level pooled meta-analysis of the DAPA-HF and DELIVER trials suggests gout was present in 10% of patients and associated with worse outcomes, but also indicate benefits of dapagliflozin were consistent in patients with heart failure regardless of whether or not they had a diagnosis of gout.

Results of the study, which included data from more than 11,000 patients with gout history available, demonstrated use of dapagliflozin was not only associated with significant reductions in the trials’ primary outcomes for patients with gout, but also associated with a reduction in the need to initiate uric acid–lowering therapy and treatment with colchicine.

“In this posthoc analysis of 2 phase 3 clinical trials, the beneficial effect of dapagliflozin use with clinical outcomes was consistent among patients with heart failure irrespective of gout status. Dapagliflozin reduced the initiation of medications used to reduce urate level or to treat gout flares, representing a meaningful additional clinical benefit of dapagliflozin in patients with heart failure,” wrote investigators.

Since the announcement of toppling results during the summer of 20222, the cardiology community has looked forward with anticipation to multiple prespecified and sub analyses from the landmark trial. Led by John McMurray, MD, professor of Cardiology at the University of Glasgow, and a multinational team, the current study was launched to investigate and provide an overview of the impact of gout on heart failure outcomes and medication use in those using dapagliflozin from the landmark DAPA-HF and DELIVER trials. Investigators designed their patient-level pooled meta-analysis to assess risk of a composite of worsening heart failure or cardiovascular death, with receipt of 10 mg dapagliflozin serving as the exposure of interest for the study.

Overall, investigators obtained data related to 11,005 patients with gout history available. Of these, 10.1% (n=1117) patients had a history of gout. Investigators noted the prevalence of gout was 10.3% in patients with reduced ejection fraction and 10.1% in those with an ejection fraction greater than 40%.

Analysis of demographic characteristics indicated patients with gout were more often men than those without (80.3% vs 63.2%) and the mean age was similar between groups, with a mean age of 69.6 (Standard deviation [SD], 9.8) years in the gout cohort and 69.3 (SD, 1.06) in the cohort without gout. However, investigators noted those with a history of gout had a higher BMI, more comorbidity, lower eGFR, and were more often treated with a loop diuretic than their counterparts without a history of gout.

Upon analysis, results indicated the rate of the study’s primary outcome was 14.7 per 100 person-years (95% CI, 13.0-16.5) in those with gout and 10.5 per 100 person-years (95% CI, 10.1-11.0) in those without gout (adjusted hazard ratio [aHR], 1.15 [95% CI, 1.01-1.31]). When assessing the effects of dapagliflozin, results demonstrated use of dapagliflozin was associated with a reduce risk of the primary endpoint to a similar extent in both those with gout (HR, 0.84 [95% CI, 0.66-1.06]) and those without gout (HR, 0.79 [95% CI, 0.71-0.87]; P=.66 for interaction). Further analysis demonstrated randomization to dapagliflozin was associated with reductions in initiation of uric acid-lowering therapy (HR, 0.43 [95% CI, 0.34-0.53]) and colchicine (HR, 0.54 [95% CI, 0.37-0.80) among patients with gout.

“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,” investigators 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 heart failure.”

References:

1. Butt JH, Docherty K, Clagget B, 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. JAMA Cardiology. February 2023. doi:10.1001/jamacardio.2022.5608
2. Iapoce C. Phase 3 deliver trial meets primary endpoint with Dapagliflozin. HCP Live. https://www.hcplive.com/view/phase-3-deliver-primary-endpoint-dapagliflozin. Published May 5, 2022. Accessed February 22, 2023.