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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.) 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. © 2017 Morales-Villegas EC MD. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Enrique C Morales-Villegas MD Statins MAbs-PCSK9 HMGCoAR 2018-02-05T18:44:29+05:30 2018-02-05T18:44:30+05:30 2018-02-05T18:44:30+05:30 5 Adobe InDesign CS6 (Windows) uuid:24ac0b80-5af0-4946-aef4-6a8366596099 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:1971EB5E760AE811A23FF003E2A94B20 proof:pdf xmp.iid:1871EB5E760AE811A23FF003E2A94B20 xmp.did:9A7BCE2A86C8E411A9F7BE0811E790A6 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2018-02-05T18:44:29+05:30 Citation: Morales-Villegas EC MD (2017) Statins-Their 3 Main Limitations The Whys of MAbs-PCSK9. JHear Health 3(1): doi http://dx.doi.org/10.16966/2379-769X.133 Morales-Villegas EC MD, Founder and Director, AguascalientesCardiometabolic Research Center, Aguascalientes, Mexico, E-mail: drmorvi@prodigy.net.mx Adobe PDF Library 10.0.1 False endstream endobj 537 0 obj <> endobj xref 0 1616 0000000000 65535 f 0000200299 00000 n 0000200740 00000 n 0000200771 00000 n 0000209789 00000 n 0000209848 00000 n 0000210302 00000 n 0000210331 00000 n 0000210466 00000 n 0000210598 00000 n 0000220000 00000 n 0000221217 00000 n 0000221504 00000 n 0000221834 00000 n 0000221919 00000 n 0000222004 00000 n 0000222064 00000 n 0000222524 00000 n 0000222684 00000 n 0000222820 00000 n 0000222953 00000 n 0000232024 00000 n 0000232109 00000 n 0000232194 00000 n 0000232254 00000 n 0000232686 00000 n 0000233718 00000 n 0000233854 00000 n 0000233987 00000 n 0000242468 00000 n 0000242553 00000 n 0000242638 00000 n 0000242698 00000 n 0000243131 00000 n 0000243579 00000 n 0000243715 00000 n 0000243848 00000 n 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0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f trailer <<299DB7DC9DCDC748866E4DECD1C9FCD4>]>> startxref 116 %%EOF 536 0 obj <>stream application/pdf Statins-Their 3 Main Limitations The Whys ofMAbs-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.) 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. © 2017 Morales-Villegas EC MD. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Enrique C Morales-Villegas MD Statins MAbs-PCSK9 HMGCoAR 2018-02-05T18:44:29+05:30 2018-02-05T18:44:34+05:30 2018-02-05T18:44:34+05:30 5 Adobe InDesign CS6 (Windows) uuid:395392fa-e6f2-4bdd-bf44-4fae1d738699 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:1971EB5E760AE811A23FF003E2A94B20 proof:pdf xmp.iid:1871EB5E760AE811A23FF003E2A94B20 xmp.did:9A7BCE2A86C8E411A9F7BE0811E790A6 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2018-02-05T18:44:29+05:30 Citation: Morales-Villegas EC MD (2017) Statins-Their 3 Main Limitations The Whys of MAbs-PCSK9. JHear Health 3(1): doi http://dx.doi.org/10.16966/2379-769X.133 Morales-Villegas EC MD, Founder and Director, AguascalientesCardiometabolic Research Center, Aguascalientes, Mexico, E-mail: drmorvi@prodigy.net.mx Adobe PDF Library 10.0.1 False endstream endobj 537 0 obj <> endobj 1617 0 obj <>/Metadata 536 0 R/Names 1618 0 R/Outlines 480 0 R/PageMode/UseOutlines/Pages 535 0 R/StructTreeRoot 538 0 R/Type/Catalog/ViewerPreferences<>>> endobj xref 0 1 0000000000 65535 f 536 2 0000429753 00000 n 0000438312 00000 n 1617 1 0000440868 00000 n trailer <]/Prev 116>> startxref 441072 %%EOF