Remnant cholesterol as a residual risk in atherosclerotic cardiovascular disease patients under statin-based lipid-lowering therapy: A post hoc analysis of the RACING trial

Abstract

Background: Remnant cholesterol (remnant-C) levels during lipid-lowering therapy (LLT) may indicate residual risk.

Objective: We aimed to investigate the clinical outcomes based on on-treatment remnant-C distribution in patients with atherosclerotic cardiovascular disease (ASCVD) under statin-based LLT.

Methods: In this post hoc analysis of the RACING trial, 3,348 patients with ASCVD lipid profiles 1 year after randomization were investigated. Remnant-C was calculated as total cholesterol minus low-density lipoprotein cholesterol (LDL-C) minus high-density lipoprotein cholesterol. The primary endpoint was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke.

Results: The study population was grouped into tertiles according to on-treatment remnant-C: high (> 20.5 mg/dL; n = 1,116), intermediate (14‒20.5 mg/dL; n = 1,031), and low (≤14.0 mg/dL; n = 1,201) remnant-C groups. The high remnant-C group showed the highest incidence of the primary endpoint at 3 years (11.0%, 10.3%, and 7.5% in the high, intermediate, and low remnant-C groups, respectively; p = 0.009). The high remnant-C levels at 1 year were independently associated with an increased risk of the primary outcome, whereas achieving LDL-C < 55 or 70 mg/dL was not associated with the incidence of the primary endpoint. The on-treatment remnant-C cut-off of 17 mg/dL (median) demonstrated the ability to discriminate between patients at higher and lower risks for the primary endpoints (hazard ratio: 1.42; 95% confidence interval: 1.14‒1.78; p = 0.002).

Conclusions: In patients with ASCVD undergoing statin-based LLT, high on-treatment remnant-C values were associated with unfavorable clinical outcomes. On-treatment remnant-C levels may serve as an additional means of assessing residual cardiovascular risk.

Clinical trial registration: ClinicalTrials. gov ID: NCT03044665.

Keywords: Atherosclerotic cardiovascular disease; Ezetimibe; Remnant cholesterol; Statin.