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Recent Fibrate Use Tied to Lower MACE Risk in Nondialysis CKD – Renal and Urology News

Recent fibrate use is associated with reduced risks for major adverse cardiovascular events (MACE) among patients with chronic kidney disease (CKD), a new Japanese study finds.

Hirohito Goto, MD, of the Center for Novel and Exploratory Clinical Trials (Y-NEXT), Yokohama City University Hospital in Kanagawa, Japan, and colleagues performed a case-control study of 15,830 patients with MACE and 31,660 without MACE. The cohort had an estimated glomerular filtration rate of 15 to less than 90 mL/min/1.73 m2.

After propensity score matching, only 3.5% of each group ever took a fibrate. Fibrate use was significantly associated with 16% decreased odds of MACE, the investigators reported in Nephrology Dialysis Transplantation. Use within the past year and current use within 30 days were significantly associated with 35% and 19% decreased odds of MACE, respectively. Past use did not appear consequential.

According to Dr Goto’s team, the findings suggest the importance of continuous fibrate therapy for cardioprotective benefits.

Drug type also mattered. Current pemafibrate use was significantly associated with 27% decreased odds of MACE compared with no current use. Current bezafibrate and fenofibrate use were not associated with MACE risk.

“Pemafibrate, a more potent and selective activator peroxisome proliferator-activated receptor-alpha, may lead to more effective lipid-lowering effects, fewer drug-drug interactions, and fewer side effects compared with older fibrates,” Dr Goto’s team wrote. They noted that fenofibrate and bezafibrate are mainly excreted via the kidneys, whereas pemafibrate is primarily metabolized in the liver and excreted via bile.

This study was based on real-world data from a large Japanese administrative database. The median age was 81 years, and many patients were at high risk for MACE. However, the study was observational without adjustment for relevant confounders, limiting its conclusions.

Randomized trial results published in The New England Journal of Medicine in 2022 found no MACE protection from pemafibrate use in patients with type 2 diabetes, but patients with CKD were excluded.

References:

Goto H, Iseri K, Hida N. Fibrates and the risk of cardiovascular outcomes in chronic kidney disease patients. Nephrol Dial Transplant. Published online November 27, 2023. doi:10.1093/ndt/gfad248