The following is a summary of “Estimated Lifetime Benefit of Combined RAAS and SGLT2 Inhibitor Therapy in Patients with Albuminuric CKD without Diabetes” published in the December 2022, issue of Nephrology by Vart et, al.
Patients with chronic kidney disease (CKD) who don’t have diabetes have a high risk of complications, yet they don’t use many effective treatments. The clinical benefit of therapy may be easier to execute if expressed in terms of additional years of life unaffected by the disease or death. Researchers estimated lifetime survival free of kidney failure for patients with albuminuric CKD without diabetes treated with the combination therapy of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and sodium-glucose cotransporter-2 (SGLT2) inhibitors relative to patients not treated. Combination therapy’s benefit over placebo was derived from trial-level estimates of the effects of ACEI/ARB treatment (ramipril/benazepril; n=690) and SGLT2 inhibitor treatment (dapagliflozin; n=1398).
Using this effect, researchers estimated the treatment effect of combination therapy to the active treatment group of patients with albuminuric CKD without diabetes participating in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (n=697) and projected event free and overall survival for those treated and not treated with combination therapy. Researchers also did the math, assuming that adherence would be lower and the benefits would be less dramatic than those seen in the current trials. Serum creatinine doubling time, kidney failure, or death were the primary endpoints. Combination therapy with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SGLT2 inhibitors was associated with a 35% lower risk of the primary endpoint than no treatment (95% CI, 0.20-0.41).
The estimated survival free from the primary composite endpoint for a patient starting at age 50 and living to age 75 with the combination therapy was 17.0 (95% CI, 12.4 to 19.6) years, compared to 9.6 years (95% CI, 8.4 to 10.7) with no treatment with any of these agents, equating to a gain in event-free survival of 7.4 (95% confidence interval, 6.4 to 8.7) years. The increase in event-free survival ranged from 5.3 years (95% CI, 4.4 to 6.1) to 5.8 years (95% CI, 4.8 to 6.8) when lower adherence and less pronounced efficacy of combination therapy were assumed. In patients with albuminuric CKD without diabetes, treatment with the combination of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SGLT2 inhibitors is anticipated to increase kidney failure-free survival significantly.