#3248 comparative effectiveness of diuretics and calcium channel blockers on top of rasi on ckd progression and mortality: a nationwide cohort study

Abstract Background and Aims It is unknown whether initiating diuretics on top of renin-angiotensin system inhibitors (RASi) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs) in persons with CKD. Method We emulated a target trial in the Swedish Renal Registry 2007–2022, enrolling patients with moderate-advanced CKD under nephrology care who had good adherence to RASi and initiated antihypertensive therapy with either diuretics or CCB. Using propensity score-weighted cause-specific Cox regression, we compared risks of major adverse renal events (MAKE, including kidney replacement therapy [KRT], ≥40% decline in eGFR, eGFR<15 mL/min per 1.73 m²), major cardiovascular events (MACE, including CV death, myocardial infarction, stroke) and death. Results We identified 5875 patients (median age 71 years, 64% men, eGFR 26 mL/min per 1.73 m²), of whom 3165 started diuretics and 2710 CCB. After a median follow-up of 6.3 [3.2-9.7] years, 2558 MAKE and 1178 MACE occurred, and 2299 deaths (Figure). Compared to CCB, diuretic use was associated with a lower risk of MAKE (adjusted HR: 0.87 [95%CI: 0.77-0.97]), consistent across single components (KRT: 0.77[0.67-0.88], ≥40% eGFR decline: 0.81[0.72-0.91], and eGFR <15mL/min/1.73 m²: 0.85[0.75-0.97]). The risks of MACE (1.15 [0.96-1.36]), all-cause (1.07 [0.94-1.22]), CV- (1.20 [0.95-1.51]) and non-CV death (1.01 [0.86-1.19]) did not differ between therapies. Results were consistent across subgroups and robust to competing risks. Conclusion Our findings provide evidence from real-world clinical practice that in patients with moderate-advanced CKD, add-on antihypertensive therapy to RASi with diuretics may confer further kidney benefits and similar cardioprotection compared with CCBs.