Study Reveals Impact of Cholesterol Changes on Cardiovascular Disease Risk

The PROMINENT trial, focusing on the triglyceride- and remnant cholesterol-lowering agent pemafibrate, demonstrated neutral results in cardiovascular outcomes despite notable reductions in plasma triglycerides and remnant cholesterol. This study aimed to explore whether absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B could elucidate the trial's outcomes.

In the trial, pemafibrate treatment led to a -7 mg/dL change in remnant cholesterol, a +10 mg/dL change in LDL cholesterol, and a +5 mg/dL change in apolipoprotein B. The Copenhagen General Population Study (CGPS) mirrored these changes to estimate their impact on atherosclerotic cardiovascular disease (ASCVD) risk, defined by cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization.

The analysis revealed hazard ratios for ASCVD of 0.97 for a -7 mg/dL change in remnant cholesterol, 1.04 for a +10 mg/dL change in LDL cholesterol, and 1.02 for a +5 mg/dL change in apolipoprotein B. When combining these changes, the estimated hazard ratio for ASCVD was 1.05 in the CGPS, closely aligning with the 1.03 observed in the PROMINENT trial.

These findings suggest that while pemafibrate effectively alters lipid profiles, the combined effects of these changes on ASCVD risk are minimal, underscoring the complexity of lipid management in cardiovascular disease prevention.