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New research leveraging trial-level estimates of the effects of combined renin-angiotensin-aldosterone system (RAAS) inhibition and SGLT2 inhibitor use suggests such an approach could contribute to extending life without kidney failure or mortality by more than 7 years for a 50-year-old patient.
An analysis using estimates of treatment effects observed in the REIN, Guangzhou, and DAPA-CKD trials, results of the study demonstrate use of combination RAAS/SGLT2 inhibition was associated with a gain in event-free survival of 7.4 years for a 50-year-old patient compared against placebo therapy among a cohort of patients with albuminuric chronic kidney disease without diabetes.
“The present study provides estimates of treatment benefit expressed in extra years free from the disease or death that is easy to understand for patients, clinicians, and policymakers. This may facilitate risk communication in clinical management, increase uptake of these therapies in clinical practice, and inform decision-making by policymakers and payers,” the authors wrote.
As more and more data details the benefits of SGTL2 inhibitors in patient populations with and without diabetes, application of treatment effects has become a research interest for many. In the current study, Priya Vart, PhD, of the University Medical Center Groningen, and colleagues sought to estimate lifetime survival free of kidney failure for patients with chronic kidney disease without diabetes.
The indirect estimates of treatment effects with ACE inhibitors/ARBs were determined through an analysis of data from the REIN and Guangzhou trial. From these trials, which examined the use of ramipril and benazepril, investigators obtained information related to the effects of ACE inhibitor/ARB use in a cohort of 690 patients. Indirect estimates of the treatment effect of combination therapy for dapagliflozin was obtained from the DAPA-CKD trial, which provided investigators with information related to the effects of SGLT2 inhibitor use in a cohort of 1398 patients.
With these indirect estimates, investigators planned to estimate the treatment effects of combination therapy among patients with albuminuria chronic kidney disease without diabetes participating in the DAPA-CKD trial, which resulted in a cohort of 697 individuals for inclusion in the investigators’ analyses. The primary outcome of interest for the trial was a composite of doubling of serum creatinine, kidney failure, or death. The secondary outcome of interest for the trial was a composite of sustained doubling of serum creatinine or kidney failure.
Upon analysis, results indicated the HRs for combination therapy compared against placebo or no treatment was 0.35 (95% CI, 0.30 to 0.41) for the primary composite endpoint and 0.33 (95% CI, 0.27 to 0.41) for the doubling of serum creatinine or kidney failure. Further analysis demonstrated, between the age of 50-75 years, the estimated survival-free years from the primary composite outcome measure was 17.0 (95% CI, 12.4-19.6) with combination therapy and with no treatment, which resulted in a difference of 7.4 years between the groups. When assessing for the secondary composite outcome, the corresponding gain in event-free survival was 8.0 (95% CI, 6.3-9.6) years.
Further analysis of the primary outcome of interest demonstrated gains in event-free survival relative to no treatment at the ages of 55, 60, and 65 years were 5.6 years (95% CI, 4.8-6.6), 3.6 years (95% CI, 3.0-4.2), and 2.8 (95% CI, 2.3-3.3), respectively. For the secondary outcome, the gains in survival seen for those at 55, 60, 65, and 70 years were 5.9 years (95% CI, 4.6 to 7.2), 3.2 years (95% CI, 2.5 to 4.0), 2.4 years (95% CI, 1.8-3.0), and 0.6 years (95% CI, 0.5 to 0.8), respectively.
In an editorial, Evan Zeitler, MD, and Amy K. Mottl, MD, both of the University of North Carolina, commended investigators for their work and expressed excitement over the recent revolution in nephrology.
"The work by Vart et al. thus provides the first clear, evidence-derived assessments of the tangible benefits of combination ACEi/ARB and SGLT2i therapy to patients with albuminuric, nondiabetic kidney disease," wrote the pair. "These data provide an entryway for nephrology to implement goal-directed medical therapy in CKD. Such information will prove invaluable for providers, both in how they balance the risks and benefits of therapy and in joint decision-making."
This study, “Estimated Lifetime Benefit of Combined RAAS and SGLT2 Inhibitor Therapy in Patients with Albuminuric CKD without Diabetes,” was published in the Clinical Journal of the American Society of Nephrology.