I-PCSK9 inhibitors ibonisa isithembiso, kodwa sifuna ulwazi oluninzi
Iqela elitsha le-anti-cholesterol izidakamizwa-i-PCSK9 inhibitors-yenza i-buzz eninzi ngaphakathi kwimizimba yabantu, kunye neengxelo ezahlukeneyo zibonisa ukuba ezi ziyobisi zintsholongwane zinokuba yinto engcono kakhulu kwizigulane ezinobunzima ukuthatha ama- statins . I-PCSK9 inhibitors zokuqala-i-Repatha (evolucumab) kunye ne-Praluent (alirocumab) -yivunyelwe ukusetyenziswa ngo-2015.
Izidakamizwa ze-PCSK9 ze-inhibitor zingabonakalisa intsebenzo enkulu kwi-cholesterol-yehlisa.
Nangona kunjalo, ukhuseleko lwabo lwexesha elide nelokusebenzayo alukasekwe ngokupheleleyo. Oko, kunye neendleko zabo eziphezulu kakhulu, kushiya oogqirha abaninzi abanokuqiniseka namhlanje kwindawo yabo efanelekileyo kwiyeza zonyango.
I-PCSK9 Inhibitors isebenza njani?
Ezi zi yobisi zivimbela umlawuli we-cholesterol othiwa "proprotein convertase subtilisin / kexin 9" (PCSK9) esibindi. Ubomi beeseli zesibindi ziqukethe i-LDL receptors, ezibopha iindidi zeLDL (eziqulethe i- LDL cholesterol ) kwaye zisuse egazini. Zomibini izintlu zeLDL kunye ne-LDL receptors zihanjiswe kwiiseli zesibindi, apho izintlu zeLDL ziphukile. Ama-receptors e-LDL abuye abuyele phezulu kwiseli yesibindi, apho 'angabamba' ezinye iindidi ze-LDL.
I-PCSK9 yiprotheyini elawulayo ebophelela kwi-LDL receptors. I-LDL receptors eziboshwe yi-PCSK9 azibuyiswa kwakhona kwi-cell surface, kodwa kunoko zidilizwe ngaphakathi kwiseli.
Ngako oko, i-PCSK9 imisela umlinganiselo wesibindi ukususa i-LDL cholesterol egazini legazi. Ngokuvimbela i-PCSK9, la machiza amatsha aphucula ngokuphumelelayo amandla okubamba ukususa i-cholesterol ye-LDL, nokunciphisa amazinga egazi le-LDL.
Xa i-PCSK9 inhibitor yongezwa kwi-dose ephezulu yonyango, i-LDL i-cholesterol imilinganiselo iqhutshwa rhoqo ngezantsi kwe-50 mg / dL, kwaye rhoqo i-25 mg / dL okanye ngaphantsi.
I-PCSK9 Inhibitors
Xa iprotheni yokulawula i-PCSK9 ifunyenwe kwiminyaka ye-2000 yokuqala, izazinzulu ziqaphela ngokukhawuleza ukuba ukuvinjelwa kweli protein kufuneka kubangele amanqanaba e-LDL ayencitshiswa kakhulu. Iinkampani zamachiza ziqalise ngokukhawuleza emncintiswaneni ukuphuhlisa i-PCSK9 inhibitors.
Ngokuphawulekayo, ezimbini zezi zi yobisi sele ziphuhlisiwe kwaye zivavanywa kwizilingo zonyango: i-evolucumab (i-Repatha, ephuhliswe ngu-Amgen) kunye ne-alirocumab (eyixabiso, ephuhliswe nguSanofi no-Regeneron). Zombini ezi zi yobisi ziyi- antibodies , zenzelwe ukuba zibe nefuthe kuphela kwi-PCSK9, kwaye (ngokoqobo, ubuncinane) naphi na enye indawo. Zibini zilawulwa yintsimbi engaphantsi (njengokwelapha kwe-insulin), kwaye inikwa kanye okanye kabini ngenyanga.
Uvavanyo lwezonyango kunye ne-PCSK9 Inhibitors
Izilingo zakuqala zonyango zaqhutyelwa nge-evolucumab (izilingo ze-OSLER) kunye ne-alirocumab (i-ODYSSEY trials), eyenzelwe ukuvavanya ukhuseleko kunye nokunyamezela kwezi zixhobo ezintsha.
Kulezi zilingo, izigulane ezingaphezulu kwe-4500 ezineengqungquthela ze-cholesterol ezibonakaliswe nzima ukunyanga zifumene enye okanye ezinye zezi zi yobisi. Izigulane zazingenakulinganiswa ukuba zifumane i-PCSK9 inhibitor kunye nesigxina se-statin, okanye i- statin drug kuphela. Qaphela ukuba akukho zigulane zaphathwa kuphela nge-PCSK9 inhibitor.
Bonke abathathi-nxaxheba bathatha ama-statins.
Iziphumo kuzo zonke izilingo zazifanayo-i-LDL ye-cholesterol yancitshiswa kwizigulane ezithatha i-PCSK9 inhibitor ngamaphesenti angaba ngu-60, xa kuthelekiswa namaqela okulawula aphathwa nge-statin yedwa. Ezi zilingo zakuqala azenzelwe ngokukodwa ukulinganisa ukuphucula kwimiphumo ye-cardiovascular, kodwa iziphumo eziphawuliweyo kubantu abanomdla wokufumana i-PCSK9 inhibitor babethembise ithemba.
Ekupheleni konyaka we-2016 uvavanyo lwe-GLAGOV lubonise ukuba, ngo-968 abantu abaneengxaki ze- coronary disease (CAD) abangazange bafumane unyango nge-evolocumab kunye ne-statin okanye i-statin yedwa, abo bafumana i-evolocumab abanamava (ngokwemyinge) i-1% iipatques zabo-i- atherosclerotic plaques- isiphumo esihle kakhulu.
Isilingo sokuqala esilungiselelwe ukuvavanya iziphumo zekliniki kwi-PCSK9 inhibitor, isilingo se-FOURIER, sanyatheliswa ekuqaleni kuka-2017. Esi sifundo esikhulu sabhalisa abantu abangaphezu kwama-27,000 abane-CAD, kwaye kwakhona bahlaziywa ukuba bafumane i-evolocumab kunye ne-statin ngokumalunga ne-statin yedwa. Emva kwexesha elilandelelanayo lokulandelela kweenyanga ezingama-22, iziphumo zekliniki kwiqela le-evolocumab zaziphuculwe kakhulu kwiqondo lokubala, nangona kunjalo nje kuphela. Ngokukodwa, umngcipheko wokuhlaselwa kwintliziyo wancitshiswa ngama-1.5 ekhulwini, umngcipheko wokufuna unyango olusasazekayo lulona ngama-1.5 ekhulwini kunye nomngcipheko wokuhlaselwa ngesifo se-0.4 pesenti. Iziganeko zokufa azizange zinciphise. Nangona kunokwenzeka ukuba ubukhulu beenzuzo zeklinikhi ziya kuphucula ngamaxesha amaninzi okulandelelana, ukubhalwa kweminye imeko leyo iya kuthatha iminyaka embalwa.
Iimpawu eziPhakathi Nge-PCSK9 Inhibitors
Izifundo zekliniki kunye ne-PCSK9 inhibitors, ininzi yezigulane zinezinye iziphumo zecala-ikakhulukazi iziphumo zesikhumba kwisayithi yokuxilongwa, kodwa iimpendulo ezingathandekiyo zibandakanya intlungu yesisu (efana neempembelelo zesistim zeemimiselo ) kunye neengxaki ze-neurocognitive (ngokukodwa, i-amnesia kunye nokukhubazeka kwememori). Kwisifundo sokuqala esi siphumo sokugqibela sasibonakala kwi-1 ekhulwini yezigulane ezingazange zenziwe kwi-PCSK9 inhibitor.
Isiganeko seengxaki ezinengqiqo , ngelixa liphantsi, sele liphakanyise iiflegi zokulumkisa. Kwisifundo esincinci sesilingo se-FOURIER, kwakungekho nantlukwano ebalulekileyo kwimisebenzi yokuqonda phakathi kwabantu abafumana i-evolocumab kunye ne-statin, xa kuthelekiswa nabantu abafumana i-statin yedwa. Nangona kunjalo, umbuzo uhlala nokuba ukuqhuba amazinga e-cholesterol kumazinga aphantsi kakhulu ixesha elide kunokunyusa umngcipheko wokuncipha kwengqondo, nokuba yintoni na iziyobisi zisetyenziselwa ukwenza njalo. Kwakhona, ixesha elide lokulandelelana lifuneka ukuze ufumane ingxaki engcono kulo mbuzo obalulekileyo.
I-PCSK9 Inhibitors kwi-Perspective
I-PCSK9 inhibitors ingaba yinto ebalulekileyo ekupheni i-cholesterol, kunye nokunciphisa ingozi yomzimba. Nangona kunjalo, nangona yonke intshiseko iboniswa ngabaninzi be-cardiologists, sifanele sigcine izinto ngendlela efanelekileyo ngoku.
Okokuqala , ngelixa iziphumo zentliziyo yegazi kunye nalezi zonyango zibonakala ziphuculwe kakhulu (kwizifundo ezincinci zexesha elifutshane), ubukhulu bokuphuculwa ngoku kude kubekho mkhulu kakhulu. Kuya kufuneka ukuba ulandele ixesha elide eliza kubona ukuba luncedo luni le mveliso-kwaye, ngokukodwa, ukuba ngaba ekugqibeleni baya kunika inzuzo yokufa kwexesha elide.
Okwesibini , njengazo zonke izidakamizwa "zonyango" zanamhlanje (izilwanyana ezenzelwe iinjongo ezithile), i-PCSK9 inhibitors zibiza kakhulu. Ukusetyenziswa kwabo, ubuncinci kwiminyaka yokuqala, ngokuqinisekileyo kuya kubalwa kubantu abasengozini enkulu kakhulu, kwaye ingozi yabo ayikwazi ukuncitshiswa kakhulu kunye nama-statins-njengabantu abane -hypercholesterolemia .
Okwesithathu , ngelixa ezi zinyango zixutywa malunga nentshukumo yonyango, kufanele siqaphele ukuba izilingo zamachiza kuze kube yiminyaka ziye zazisebenzisa ngokubhekisele kwiimimiselo, kungekhona esikhundleni seemimiselo. Ngoko, asinayo idatha yeklinikhi ukuze asitshele ukuba ingaba yinto enokuthi ibenokuba ngabadlali abasebenza ngokusemthethweni.
Okwesine , ngelixa iprogram yezokhuseleko ze-PCSK9 zize zibukeka zithembise, zihlala zibuza imibuzo evulekile; ngokukodwa, ngokubhekiselele ukuba ukuqhuba i-cholesterol kumazinga aphantsi aphantsi kwithuba elide lingase libe yinto engabalulekanga, ingakumbi ngokubhekiselele kumsebenzi wokuqonda.
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