Cardiovascular outcomes of triglyceride-targeting lipid-lowering therapies in patients with CKD.

Introduction In patients with CKD, atherogenic lipid profiles, characterized by hypertriglyceridemia and impaired high-density lipoprotein cholesterol (HDL-C) metabolism, contribute to adverse cardiovascular disease (CVD) outcomes. Since evidence on CVD outcomes of triglyceride-targeting lipid-lowering therapies (LLTs), such as fibrates and niacin, remains limited, kidney disease guidelines recommend further investigation. Methods We designed this retrospective cohort study using a target trial emulation framework and leveraged data from a nationwide cohort of 3,562,882 US Veterans to identify 46,904 incident CKD patients initiating de novo fibrate, niacin, or statin therapy. We compared the risk of major adverse cardiovascular events [MACE] (composite of acute myocardial infarction, ischemic stroke, congestive heart failure, or all-cause death) using Cox proportional hazards models adjusted for baseline covariates during follow-up of up to 10 years. Results 16,191 patients (event rate, 79.21 [95% CI: 78.0, 80.43] per 1000 person-years) experienced MACE after a median follow-up of 3.70 years. The risk of MACE was significantly lower (HR, 0.93 [95% CI, 0.86, 0.99]; p=0.03) in de novo fibrate users compared to statin users. Niacin users, however, did not have a significantly different risk of MACE (1.03 [0.95, 1.12], p=0.42) than statin users. The result was largely attributable to the association between fibrate use and CHF: a statistically significant 13% lower hazard (0.87 [0.78, 0.96]; p=0.005) compared with statin use. Conclusion In this large nationwide cohort of patients with non-kidney replacement therapy-dependent CKD, de novo fibrate use, but not niacin use, was associated with a lower risk of MACE than de novo statin use.