Statins-Their 3 Main Limitations The Whys of MAbs-PCSK9

This review analyses three of the most relevant statins therapeutic limitations, named familial hypercholesterolemia, high risk and statins therapeutic variability and statins muscular-intolerance. Familial hypercholesterolemia has been the engine for important discoveries such as LDLR and statins; the use of these has changed the natural history of ASCVD in these individuals. However, for subjects with the homozygous and to a lesser extent for individuals with the heterozygous forms, the therapeutic effect of statins is not sufficient to achieve optimal levels of LDLcholesterol; in this paper, we will review the etiology, prevalence, diagnosis, evolution, treatment and new therapeutic options for this disease. Therapeutic variability is a very common clinical issue, in a given population, the administration of a statin of medium or high intensity reduces on average 30% or 50% the level of LDL-cholesterol. However, there is wide inter-individual and intra-individual variability in treatment with any HMGCoAR inhibitor. Both types of variability have prognostic implications and therefore their knowledge is important. The transcendence of the inter- and intra-individual therapeutic variability of statins supports the personalized approach in their use and justifies in a variable percentage the potential use of the MAbs-PCSK9, especially in high and very high risk individuals. Finally, since statin intolerance is a nonspecific concept wich may include muscle (myalgias and CPK increase) or non-muscle related (AST-ALT increase, neurocognitive abnormalities, gastrointestinal symptoms, etc.) adverse events associated with HMGCoAR inhibitors; in order to be more specific, the term Statin-Associated Muscle Symptoms or SAMS has been proposed. The reported prevalence of this problem varies widely from 30% in observational studies to <10% in “double-blind” studies. Statin muscle-intolerance is the most common cause for treatment discontinuation and is in turn an important risk factor for ASCVD, because that, it is essential to establish a correct diagnosis of SAMS and efficient alternative therapeutic strategies; thus, SAMS is another important and potential therapeutic “niche” for MAbs-PCSK9 commented in this review.