Very low LDL-C levels may safely provide additional clinical cardiovascular benefit: the evidence to date.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in Europe and increased low-density lipoprotein cholesterol (LDL-C) is a major contributor to CVD risk. Extensive evidence from clinical studies of statins has demonstrated a linear relationship between LDL-C levels and CVD risk. It has been proposed that lower LDL-C levels than those currently recommended may provide additional clinical benefit to patients. AIM: This review summarises the genetic and clinical evidence on the efficacy and safety of achieving very low LDL-C levels. METHODS: Relevant epidemiological and clinical studies were identified using PubMed and by searching abstracts published at major congresses. RESULTS: Genetic evidence demonstrates that individuals with naturally very low LDL-C levels are healthy and have a low risk of CVD. Clinical evidence has shown that those patients who achieve very low LDL-C levels through using lipid-lowering therapies (LLTs), such as statins, have reduced CVD risk compared with patients who only just achieve recommended target LDL-C levels. These data show that the incidence of adverse events in patients achieving very low LDL-C levels using LLT is comparable to those reaching the recommended LDL-C targets. CONCLUSIONS: Genetic and clinical evidence supports the concept that reduction in LDL-C levels below current recommended targets may provide additional clinical benefit to patients without adversely impacting patient safety. Statin add-on therapies, such as ezetimibe and the recently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab, allow patients to achieve very low LDL-C levels and are likely to impact on future treatment paradigms.