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

Jaeoh Lee; Sripal Bangalore; Kyeong Ho Yun; Sang-Hyup Lee; Yong-Joon Lee; Seung-Jun Lee; Sung-Jin Hong; Chul-Min Ahn; Jung-Sun Kim; Byeong-Keuk Kim; Young-Guk Ko; Donghoon Choi; Yangsoo Jang; Bum-Kee Hong; Myeong-Ki Hong

doi:Purpose: 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.

Materials and methods: 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.

Results: 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; p<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%.

Conclusion: 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.

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

Authors: Jaeoh Lee ; Sripal Bangalore ; Kyeong Ho Yun ; Sang-Hyup Lee ; Yong-Joon Lee ; Seung-Jun Lee ; Sung-Jin Hong ; Chul-Min Ahn ; Jung-Sun Kim ; Byeong-Keuk Kim ; Young-Guk Ko ; Donghoon Choi ; Yangsoo Jang ; Bum-Kee Hong ; Myeong-Ki Hong

Citation: YONSEI MEDICAL JOURNAL, Vol.66(9) : 537-544, 2025-09

Journal Title: YONSEI MEDICAL JOURNAL

ISSN: 0513-5796

Issue Date: 2025-09

MeSH: 0

Keywords: 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 ; Prognosis ; Randomized Controlled Trials as Topic ; Stroke

Abstract: Lipid-lowering therapy ; atherosclerotic cardiovascular disease ; cardiovascular outcome ; low-density lipoprotein cholesterol

Article Number: 10.3349/ymj.2024.0476

DOI: Purpose: 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. Materials and methods: 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. Results: 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; p<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%. Conclusion: 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.

Appears in Collections:: 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

URI: https://ir.ymlib.yonsei.ac.kr/handle/22282913/207505

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