3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) (HMGCR)

3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the rate-limiting enzyme in the mevalonate pathway, responsible for the endogenous production of cholesterol in the liver (UniProt P04035). By converting HMG-CoA into mevalonate, it serves as a critical control point for lipid metabolism and the synthesis of isoprenoids (StatPearls). In clinical practice, HMGCR is the primary therapeutic target for statins, which are used to lower low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular event risk (PubMed, PMID: 31840167). The combination of HMGCR inhibition with omega-3 carboxylic acids (OM3-CA) is employed to treat mixed dyslipidemia, addressing both elevated LDL-C and high triglycerides (AHA/ACC Guidelines). While statins lower cholesterol, OM3-CA provides complementary reduction of triglyceride-rich lipoproteins, though large-scale trials like STRENGTH have investigated the overall cardiovascular benefit of this specific combination (JAMA, 2020). This therapeutic strategy aims to manage residual cardiovascular risk in patients who remain at high risk despite optimized statin therapy.

Other names

HMG-CoA reductase3-hydroxy-3-methylglutaryl-Coenzyme A reductaseHMGCR

Statins act as competitive inhibitors of HMGCR, blocking the conversion of HMG-CoA to mevalonate, which triggers an increase in hepatic LDL receptor expression and subsequent clearance of circulating LDL-C (StatPearls). In the context of combination therapy, Omega-3 carboxylic acids (OM3-CA) complement this by reducing hepatic triglyceride synthesis and increasing the clearance of triglycerides from circulating VLDL particles (PubMed, PMID: 25149866).