#3669 EFFECT OF DAPAGLIFLOZIN IN PATIENTS WITH CKD ACROSS THE SPECTRUM OF AGE AND BY SEX
Authors: Yu Margaret , Vart Priya , Heerspink Hiddo Lambers , Jong Niels , Correa-Rotter Ricardo , Mcmurray John , Rossing Peter , Langkilde Anna Maria , Toto Robert , Wheeler David C , Chertow Glenn 
Published: June 2023

Abstract

Background and Aims
The SGLT2 inhibitor dapagliflozin reduces the risk of progressive kidney disease and cardiovascular events in patients with and without type 2 diabetes. Among patients with CKD, baseline risks of cardiovascular disease and CKD progression vary based on age and sex. Whether the effects of dapagliflozin are uniform among patients across the spectrum of age and among men and women is unknown. Therefore, we performed a pre-specified analysis from the DAPA-CKD trial to evaluate efficacy and safety of dapagliflozin according to baseline age and sex.

Method
We randomized 4304 adults with baseline estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio 200–5000 mg/g to dapagliflozin 10 mg or placebo once daily. The primary endpoint was a composite of ≥50% eGFR decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary endpoints included a kidney composite endpoint (primary composite endpoint without cardiovascular death), a cardiovascular composite endpoint (hospitalized heart failure or cardiovascular death), and all-cause mortality. Study participants were categorized based on decades of age (&lt;50, 50-59, 60-69, 70-79, and ≥80 years). Sex was based on self-report. We conducted time-to-event analyses using a proportional hazards (Cox) regression stratified by randomization factors (diabetes status and UACR), adjusting for baseline eGFR, and analyzed the effects of dapagliflozin on total and chronic eGFR slopes using a mixed effects linear spline model.

Results
Median follow-up was 2.4 years. 671 (15.6%), 935 (21.7%), 1501 (34.9%), 999 (23.2%), and 198 (4.6%) participants were &lt;50, 50-59, 60-69, 70-79, and ≥80 years of age, respectively; 1425 (33.1%) were women and 2879 (66.9%) were men. Racial composition varied by age and sex; older patients were more likely to be white, younger patients were more likely to be Asian, and a higher proportion of women were black. As expected, absolute risks of the cardiovascular composite endpoint and all-cause mortality were higher in older patients; absolute risks of the kidney composite endpoint were highest in patients &lt;50 (10.7 and 6.2 per 100 patient-years in the placebo and dapagliflozin groups, respectively) and lowest in patients ≥80 years (3.0 and 1.2 per 100 patient-years in the placebo and dapagliflozin groups, respectively). There was no evidence of heterogeneity of the relative effects of dapagliflozin on the primary composite or secondary endpoints based on age or sex. Neither age nor sex modified the effects of dapagliflozin on total or chronic eGFR slope (Figure 1).

Conclusion
Benefits of dapagliflozin were evident across the spectrum of age and among women and men. Although younger trial participants with CKD and albuminuria were more likely to experience CKD progression, dapagliflozin reduced the risks of mortality, cardiovascular events, and CKD progression in older patients, including in more than 25% septuagenarians and octogenarians. Ageism and/or therapeutic nihilism should not diminish the use of dapagliflozin in older patients who are likely to experience considerable benefit.