Kuze kube maduzane, odokotela abaningi babhekisela ku-cholesterol-diet-CHD hypothesis. Okokuqala, amazinga aphezulu we-cholesterol egazini noma e-hypercholesterolemia enza imbangela ye- coronary heart (CHD). Okwesibili, ukudla okucebile ngamafutha ezilwane kanye ne-cholesterol kwandisa amazinga e-cholesterol egazini. Okwesibili, ukwehlisa amazinga e-cholesterol egazini kunciphisa ingozi ye-coronary heart disease.
Ngesikhathi sokubheka ubuso, i-cholesterol-diet-CHD hypothesis ibonakala inengqondo. Ngempela, "yilokho esikudlayo," futhi uma sidla ukudla okunomsoco we-cholesterol kanye namafutha (izilwane) ezigcweleyo, amazinga wegazi we-cholesterol angase akhuphuke. Ngaphezu kwalokho, ngoba ama-plaques-ama-clog arteries futhi abangela i-CHD kanye nesifo sohlangothi-ziyingxenye eyakhiwe yi-cholesterol, amazinga akhudlwana we-cholesterol egazini elidlula ekudleni okwandisa ingozi ye-CHD nokushaywa isifo. Futhi, uma ngabe wehlisa amazinga e-cholesterol egazini lakho usebenzisa imithi, khona-ke wehlisa ingozi yakho ye-CHD nokushaya, ngokulungile? Yebo, ngokuqondene nazo zonke lezi zicabango, akunakwenzeka.
Iningi lwakamuva, kube khona ushintsho olwandle ezimisweni ezilawula ukuphathwa kwe-CHD. Asiqiniseki ukuthi ukudla okunomsoco we-cholesterol namafutha agcweleyo kunesibopho ngqo kumazinga akhule we-cholesterol egazini. Ngaphezu kwalokho, asiqiniseki ukuthi ukwehlisa amazinga egazi we-cholesterol kulabo abasengozini yesifo senhliziyo kusiza ukuvimbela isifo, ingculaza engaqiniseki, ukuhlasela kwenhliziyo nokuningi.
Konke esikwaziyo ukuthi ukuguqula indlela yokuphila (isibonelo, ukulahlekelwa isisindo, ukuvivinya umzimba nokuqeda ukubhema) kanye nezitembu, noma izidakamizwa ezifana neZocor ne-Crestor, ezizinzisa izikhala futhi zenzeke ngaphansi kwe-lipoprotein cholesterol (LDL-C) ephansi "cholesterol" embi, mhlawumbe kusiza ukuvimbela ukufa kanye nezinye izenzakalo zenhliziyo ezimbi,
U-Evolocumab ungowesigaba esisha semithi. Ekuvivinyweni kwemitholampilo kuboniswe ukuthi kunciphise ngokushesha amazinga e-LDL-C kubantu abahlukahlukene ababambe iqhaza-ikakhulukazi kulabo abane-genetic disorder ebizwa ngokuthi i-hypercholesterolemia yomndeni eyenza ama-cyclopean (ngempela, aphezulu) ama-cholesterol egazini. Manje ngabe i-evolocumab izoletha noma iyiphi inzuzo kubantu abaningi abasengozini yokufa kanye nezenzakalo ezimbi ezibangelwa yi-coronary disease disease ezihlala zibonakala, futhi ngokuyincike zixhomeke emibhalweni yokufunda isikhathi eside noma okuzoba khona lapho kubhekwa abahlanganyeli phakathi neminyaka ye-evolocumab (i-Repatha ) ukwelapha. Ngamanye amazwi, isikhathi sokuphela sizokwazisa ukuthi i-evolocumab isebenza yini.
Yini Evolocumab?
I-Evolocumab i-anti-monoclonal antibody ephelele yomuntu ehlanganisa futhi ngaleyo ndlela ivimbela amaprotheni PCSK9. Le phrotheni iphazamisa i-receptor eqoqa i-LDL-C ngokudambiswa kwesibindi futhi iphazamise ikhono le-receptor lokuphindaphinda. (Ngokuthakazelisayo, ucwaningo lukhombisa ukuthi izitembu zingase zihlele i-PCSK9, ngenye indlela, uma zisetshenziselwa ndawonye, izitembu nezombono we-evolocumab azivumelanisi kahle noma zikhona.)
Njengamanje, u-Amgen, umenzi we-evolocumab, uqhuba izilingo eziningana zemitholampilo emikhulu ezindaweni ezihlukahlukene zesiguli emhlabeni wonke.
Imiphumela yalezi zivivinyo izithembisa ngokuqondene nekhono lika-evolocumab lokunciphisa amazinga e-LDL-C. Isibonelo, kwesilingo esisodwa seSigaba sesi-3, abahlanganyeli abane-hypercholesterolemia yomndeni oyinyanya kakhulu (hypercholesterolemia yomndeni ongama-homozygous) ababenesifo somzimba (ezinye zazikhona nezinye izidakamizwa ze-cholesterol okuthiwa i-Zetia) zathola ukunciphisa ngamaphesenti angu-31 emazingeni e-LDL-C at 12 amasonto aqhathaniswa nabantu abangatholanga lesi sidakamizwa. (Abahlanganyeli nabo babhekene nokunciphisa amaphesenti angu-23 ku-apolipoprotein B.) Okubaluleke kakhulu, u-evolocumab wasebenza ngokushesha kunezinye izidakamizwa ezimbili ezishaya phansi kwepayipi: i-lomitapide ne-mipomersen.
Ukuqalisa, ngokwemiphumela emibi, i-evolocumab ibekezelela kangcono kune-omitapide ne-mipomersen.
Kwesinye isilingo sesiGaba sesi-3, abahlanganyeli ababengenakubekezela okungenani ama-statins amabili futhi baphathwa nge-evolocumab ne-Zetia kuphela babona ukwehla kwamaphesenti angu-53 kuya ku-56 ku-LDL-C uma kuqhathaniswa nokunciphisa amaphesenti angu-37 kuya ku-39 kubahlanganyeli abathola i-Zetia kuphela. Ngaphezu kwalokho, i-evolocumab yenza izenzakalo ezimbalwa ezimbi kuneZetia.
Ekugcineni, ezifundweni zeSigaba 2, kulabo abahlanganyeli abane-hypercholesterolemia futhi kakade ekusebenziseni ukwelashwa kwesimo esiphakathi kuya phezulu kuya phezulu, i-evolocumab inciphisa amazinga e-LDL-C ngamaphesenti angama-66 kuya kwangu-75 uma ephathwa kabili ngenyanga.
Ingabe Lingasiza Iziguli Ngempela?
Ngalesi sikhathi, i-jury isacishe ukuthi ngabe i-evolocumab izokwazi yini ukunikeza inzuzo yezempilo kubantu abasengozini yokuhlaselwa isifo nokushaya kwenhliziyo. Ukunciphisa amazinga e-cholesterol mhlawumbe kusho okuncane kubantu abaningi, iphuzu laqhutshwa ekhaya yiziqondiso ezintsha ze-ACC / AHA eziqedile ngokuphumelelayo amazinga "okubhekiswe" we-serum cholesterol. Ngaphezu kwalokho, le mihlahlandlela iphakamisa ukuthi izitembu, izidakamizwa kuphela ezibonisa ukuthi yikuphi ukuzuzisa ekunciphiseni ukulimala komzimba kanye nokufa, kufanele zenziwe kubantu abavele benesifo senhliziyo (ukushaya isifo noma isifo senhliziyo), abantu abanamazinga e-LDL-C angaphezu kuka-190 ( amazinga aphakeme kakhulu okuthiwa yi-cholesterol "embi"), abantu abaneminyaka engama-40 kuya ku-75 abanesifo sikashukela sohlobo lwesibili, kanye nabantu abaneminyaka engama-40 kuya ku-75 abanengozi ye-7.5% yesifo senhliziyo eminyakeni eyishumi ezayo.
Uma phakathi nokuhlolwa kokwempilo kakhudlwana okulandela izakhamuzi iminyaka eminingi, i-evolocumab ifakazela ngokuphumelelayo ekunciphiseni imiphumela yesifo senhliziyo njengesifo sohlangothi nesifo senhliziyo, bese sibheka impumelelo yemithi engaqhathaniswa nama-statins. Sibhekene nokuqinisekiswa kwe-cholesterol-yokudla-i-CHD hypothesis eye yafakazela ukuthi ayikho cishe ukuthi isekelwe eminyakeni yokuhlolwa kwesayensi. Ekugcineni, ikhono lika-evolocumab lokunciphisa amazinga e-LDL-C emiphakathini ehlukene yabantu abathintekayo likhumbuza i-blockbuster yezidakamizwa zeZetia, okuye kwafakazelwa ukuthi ayinamandla (noma ngisho neyingozi kakhulu) ekuvimbeleni ukwakha ama-plaque kubahlanganyeli bokutadisha. Ngamanye amazwi, i-Zetia yayihluleka kakhulu futhi kungenzeka ibe yi-evolocumab
> Imithombo
> "I-Anti-PCSK9 Antibody Ngokuphumelelayo Iyanciphisa I-Cholesterol Ezigulini ezine-Statin Inxerance" ngu-Erik Stroes kanye nozakwabo abashicilelwe ngo-11/23/2014 (e-pub ngaphambi kokuphrinta) ku- Journal of the American College of Cardiology.
> I-Bersot TP. Isahluko 31. Ukwelashwa Kwemithi Ye-Hypercholesterolemia ne-Dyslipidemia. Ku: Brunton LL, Chabner BA, Knollmann BC. ama-eds. Goodman & Gilman's The Baseline of Therapeutics, 12e . ENew York, NY: McGraw-Hill; 2011.
> "Umphumela we-evolocumab noma i-ezetimibe wanezela ekwenzeni ukulinganisela-noma ukuqina okunamandla kwesimiso se-LDL-C ukwehlisa iziguli ezine-hypercholesterolemia: isilingo somtholampilo se-LAPLACE-2 esihleliwe" nguJG Robinson nozakwabo abashicilelwe ku-JAMA ngo-5/14/2014.
> "Ukuvinjelwa kwe-PCSK9 nge-evolocumab ngo-homopergous family hypercholesterolemia (i-TESLA Part B): inhlolovo elawulwa yi-FB Raal kanye nosebenza nabo eshicilelwe ku-Lancet ngo-10/2/2014.