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.