Fibrates and the risk of cardiovascular outcomes in chronic kidney disease patients

Abstract

Background: The high risk of major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD) has been well described. However, the efficacy of fibrates on the risk of MACE in patients with CKD remains unclear. Methods: We conducted a nested case-control study using data from a large administrative database that included more than 1.5 million Japanese patients. We defined cases as CKD patients with incidences of MACE and matched them with controls based on age, sex, calendar year of cohort entry and CKD stage. Fibrate exposure timing was categorized as current, recent or past. A conditional logistic regression analysis was used to investigate the association between fibrate use and the risk of MACE. Results: Our study included 47 490 patients with CKD, with 15 830 MACE identified during a median follow-up of 9.4 months. The numbers of fibrates used during the study period were 556 (3.5%) in the case group and 1109 (3.5%) in the control group. Fibrate use was significantly associated with a decreased risk of MACE [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.75-0.94], particularly for current (OR 0.81; 95% CI 0.68-0.97) and recent use (OR 0.65; 95% CI 0.48-0.90). Regarding the class effect of fibrates, pemafibrate use, but not bezafibrate or fenofibrate use, was significantly associated with a decreased risk of MACE (OR 0.73; 95% CI 0.528-0.997). Conclusion: Recent and current fibrate use, especially pemafibrate use, was associated with a reduced risk of MACE in patients with CKD. This suggests the potential benefits of continuous fibrate therapy and the possible superiority of pemafibrate over other fibrates. However, further investigations in different populations are required to confirm the generalizability of these findings.