Evinacumab reduces remnant cholesterol in patients with hypercholesterolemia or hypertriglyceridemia

Abstract

Background and Aims : Natural selection (Mendelian randomization) studies support a causal relationship between elevated remnant cholesterol (RC) and atherosclerotic cardiovascular disease (ASCVD). Evinacumab, an angiopoietin-like 3 inhibitor, has previously been shown to reduce LDL-C, non-HDL-C and apolipoprotein B100 – known contributors to ASCVD. This post hoc analysis assessed evinacumab efficacy to reduce RC in patient cohorts from three separate clinical trials with evinacumab, irrespective of treatment arm.Methods: RC was calculated as total cholesterol – HDL-C – LDL-C. For the 1629 and 1643 trials, LDL-C was calculated using the Friedewald equation unless triglycerides (TGs) were >400 mg/dL, where LDL-C was determined via beta-quantification. For the 1522 trial, LDL-C was determined via beta-quantification. 1629 (NCT03399786): Patients with homozygous familial hypercholesterolemia (HoFH) and LDL-C ≥70 mg/dL were enrolled. 1643 (NCT03175367): Patients diagnosed with refractory hypercholesterolemia, and LDL-C ≥70 mg/dL or ≥100 mg/dL for those with/without ASCVD, were enrolled. 1522 (NCT03175367): Patients with severe hypertriglyceridemia (sHTG; fasting TGs ≥500 mg/dL) were enrolled. Randomization details for all three trials are provided in the Table.Conclusions: Despite limitations in comparing the study groups directly, the reductions observed suggest evinacumab treatment lowers RC. RC could be a future target for lipid-lowering therapies. Background and Aims : Natural selection (Mendelian randomization) studies support a causal relationship between elevated remnant cholesterol (RC) and atherosclerotic cardiovascular disease (ASCVD). Evinacumab, an angiopoietin-like 3 inhibitor, has previously been shown to reduce LDL-C, non-HDL-C and apolipoprotein B100 – known contributors to ASCVD. This post hoc analysis assessed evinacumab efficacy to reduce RC in patient cohorts from three separate clinical trials with evinacumab, irrespective of treatment arm. Methods: RC was calculated as total cholesterol – HDL-C – LDL-C. For the 1629 and 1643 trials, LDL-C was calculated using the Friedewald equation unless triglycerides (TGs) were >400 mg/dL, where LDL-C was determined via beta-quantification. For the 1522 trial, LDL-C was determined via beta-quantification. 1629 (NCT03399786): Patients with homozygous familial hypercholesterolemia (HoFH) and LDL-C ≥70 mg/dL were enrolled. 1643 (NCT03175367): Patients diagnosed with refractory hypercholesterolemia, and LDL-C ≥70 mg/dL or ≥100 mg/dL for those with/without ASCVD, were enrolled. 1522 (NCT03175367): Patients with severe hypertriglyceridemia (sHTG; fasting TGs ≥500 mg/dL) were enrolled. Randomization details for all three trials are provided in the Table. Conclusions: Despite limitations in comparing the study groups directly, the reductions observed suggest evinacumab treatment lowers RC. RC could be a future target for lipid-lowering therapies.