Cholesteryl ester transfer protein inhibition with obicetrapib is associated with attenuated decline in kidney function in patients at high cardiovascular risk: Post hoc pooled results from the BROADWAY and BROOKLYN trials

Patients with cardiovascular disease have increased risk of chronic kidney disease progression. Low levels of high-density lipoprotein (HDL) or HDL dysfunction have been implicated in progressive deterioration of renal function. We investigated the impact on renal function of obicetrapib, a cholesteryl ester transfer protein (CETP) inhibitor that raises apolipoprotein A1 and HDL cholesterol (HDL-C) and improves HDL function. BROADWAY ( N = 2530) and BROOKLYN ( N = 354) were double-blind, placebo-controlled trials of patients with heterozygous familial hypercholesterolemia and/or established atherosclerotic cardiovascular disease taking maximally tolerated lipid-lowering therapy assigned to 365-day treatment with the novel CETP inhibitor, obicetrapib 10 mg/d, or placebo. In a post hoc pooled trial analysis of randomized participants with at least 1 post-baseline renal assessment (estimated glomerular filtration rate [eGFR] n = 2832; urine albumin-to-creatinine ratio [UACR] n = 1897), renal function and its association with HDL-C were evaluated. Participants in BROADWAY and BROOKLYN had mean (±SD) baseline eGFR 84.4 ± 17.9 and 91.8 ± 17.8 mL/min/1.73 m² and median albumin-to-creatinine ratio 11.0 and 8.0 mg/g, respectively. Obicetrapib attenuated kidney function decline vs placebo (mean difference = 0.67 mL/min/1.73 m², nominal P = 0.02); on-treatment analysis strengthened this signal (0.82; nominal P = 0.0139). Obicetrapib-treated patients had nominally fewer cases of eGFR <15 mL/min/1.73 m 2 (0 vs 0.2 %),≥40 % eGFR declines (1.3 vs 1.9 %), and a renal events composite (1.9 vs 3.0 %; hazard ratio 0.64, nominal P = 0.08). Higher achieved HDL-C was associated with lower renal composite event risk (spline nominal P < 0.0001), independent of baseline HDL-C and eGFR. Annualized percent change in UACR was not significantly different between groups. In patients at high cardiovascular risk, CETP inhibition with obicetrapib may attenuate kidney function decline, potentially through its HDL-raising effects.