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September 10, 2025Open Access

Risk reduction of ASCVD attributed to lowering of remnant cholesterol from statins, fibrates, APOC3 inhibitors, and ANGPTL3 inhibitors: a cohort study

MBMie BallingUniversity of Copenhagen OROtto Grøn RoepstorffUniversity of Copenhagen TGThomas Alexander GerdsGeneral Cardiology

Key Points

Predicted 10-year ASCVD risk reduction of 4.1% for statin users lowering remnant cholesterol by 80%.
Average 10-year ASCVD risk at 20% for statin users and 11% for non-users with remnant cholesterol >1 mmol/L.
Cox regression model reveals significant risk reductions for remnant cholesterol therapies in high-risk populations.
Study estimates potential for new therapies to effectively lower ASCVD burden through remnant cholesterol targeting.

Abstract

Randomized clinical trials of remnant cholesterol lowering drugs show 50 % and 80 % reduction in remnant cholesterol with apolipoprotein C3 (APOC3) and angiopoietin-like 3 (ANGPTL3) inhibitors. However, how many of atherosclerotic cardiovascular disease(ASCVD) cases that could be prevented lowering remnant cholesterol by these therapies is unknown. The aim of the study was to estimate the potential of APOC3 and ANGPTL3 inhibitors to reduce the ASCVD burden through lowering of remnant cholesterol. Of 98,311 individuals from the Copenhagen General Population Study without ASCVD at study entry 8,506 were statin users and 89,805 were statin non-users. Cause-specific Cox regression was used to model rates of ASCVD and non-cardiovascular death conditional on remnant cholesterol and risk factors. Based on these models the potential 10-year absolute risk reduction of ASCVD in individuals with remnant cholesterol >1 mmol/L (>39 mg/dL) for 15 %, 30 %, 50 %, and 80 % lower remnant cholesterol was predicted. The predicted average 10-year absolute risk of ASCVD was 20 % for statin users and 11 % for statin non-users with remnant cholesterol >1 mmol/L (>39 mg/dL). The predicted 10-year absolute risk reduction of ASCVD in individuals with remnant cholesterol >1 mmol/L (>39 mg/dL) for 50 % and 80 % lower remnant cholesterol were 2.7 % (95 % confidence interval: 2.2-3.2 %), and 4.1 % (3.4-4.8 %) for statin users and 1.4 % (1.3-1.5 %), and 2.1 % (2.0-2.3 %) for statin non-users. We have shown that significant ASCVD risk reductions are expected for remnant cholesterol lowering drugs in at-risk populations, if intervention trials with novel remnant cholesterol lowering drugs show expected reductions in remnants in large cardiovascular outcomes trials.

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