Prognostic Implication of LDL-C Variability and Its Association with Lipid-Lowering Strategies: Insights from the RACING and LODESTAR Trials

• Published in: Yonsei medical journal Vol. 66; no. 9; pp. 537 - 544
• Main Authors: Lee, Jaeoh, Bangalore, Sripal, Yun, Kyeong Ho, Lee, Sang-Hyup, Lee, Yong-Joon, Lee, Seung-Jun, Hong, Sung-Jin, Ahn, Chul-Min, Kim, Jung-Sun, Kim, Byeong-Keuk, Ko, Young-Guk, Choi, Donghoon, Jang, Yangsoo, Hong, Bum-Kee, Hong, Myeong-Ki
• Format: Journal Article
• Language: English
• Published: Korea (South) Yonsei University College of Medicine 01.09.2025; 연세대학교의과대학
• Subjects: Aged; Anticholesteremic Agents - therapeutic use; Cholesterol, LDL - blood; Ezetimibe - therapeutic use; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Male; Middle Aged; Myocardial Infarction - blood; Original; Prognosis; Randomized Controlled Trials as Topic; Stroke; 의학일반; atherosclerotic cardiovascular disease; cardiovascular outcome; Lipid-lowering therapy; low-density lipoprotein cholesterol
• ISSN: 0513-5796; 1976-2437; 1976-2437
• DOI: 10.3349/ymj.2024.0476

We aimed to compare the visit-to-visit variability in low-density lipoprotein cholesterol (LDL-C) according to different lipid-lowering strategies and evaluate its prognostic implications using data from previous trials. We analyzed two randomized clinical trials: the RACING trial and the LODESTAR trial. LDL-C variability was evaluated using standard deviation (SD), coefficient of variation, and variation independent of mean. The primary endpoint was a composite of death, myocardial infarction, stroke, or coronary revascularization. Among the 6800 patients included, when compared with patients randomized to high-intensity statins, LDL-C variability was similar in the group randomized to moderate-intensity statin plus ezetimibe combination, but it was higher in those randomized to treat-to-target strategy. The variability in LDL-C (by SD) was a predictor of primary endpoint even after adjustment for lipid-lowering strategy and mean LDL-C (hazard ratio 1.024; 95% confidence interval 1.014 to 1.035; <0.001). Every 1-SD increase in LDL-C variability (SD) was also independently associated with higher risk of myocardial infarction by 2.1%, stroke by 3.5%, and coronary revascularization by 2.7%. Compared to high-intensity statin therapy, LDL-C variability was not increased with the moderate-intensity statin plus ezetimibe combination therapy; however, it was increased in the treat-to-target strategy. Even among those treated with moderate- or high-intensity statins or statins with a target LDL-C levels of 50-70 mg/dL, increased LDL-C variability was associated with higher risk of adverse cardiovascular outcomes.