I-PCSK9 inhibitors ibonisa isithembiso, kodwa sidinga ulwazi oluningi
Iklasi elisha lezidakamizwa eziphikisana ne-cholesterol-i-PCSK9 inhibitors-lidala eziningi ze-buzz ngaphakathi komphakathi wezinhliziyo, futhi imibiko ehlukahlukene iphakamisa ukuthi le mithi emisha ingase ibe yindlela engcono kakhulu yeziguli ezinenkinga yokuthatha izitembu . I-PCSK9 inhibitors yokuqala-i-Repatha (i-evolucumab) ne-Value (i-alirocumab) -yamukelekile ukusetshenziswa ngo-2015.
Imithi ye-PCSK9 ye-inhibitor ingammelela ngempela ukuphumelela okukhulu kwe-cholesterol-ukwehla.
Noma kunjalo, ukuphepha nokusebenza kwabo isikhathi eside akukakhiwa ngokugcwele. Lokho, kanye nezindleko zabo eziphakeme kakhulu, bashiya odokotela abaningi bengalokhu beqiniseka namuhla endaweni yabo efanele emithi yokwelashwa.
I-PCSK9 Inhibitors isebenza kanjani?
Lezi zidakamizwa zivimbela umlawuli we-cholesterol okuthiwa "proprotein convertase subtilisin / kexin 9" (PCSK9) esibindi. Ubuso bamangqamuzana wesibindi aqukethe i-LDL receptors, ehlanganisa ukujikeleza izinhlayiya ze-LDL (eziqukethe i- LDL cholesterol ) futhi zisuse egazini. Kokubili izinhlayiya ze-LDL kanye nama-receptors e-LDL abese athuthelwa emangqamuzaneni wesibindi, lapho izinhlayiya ze-LDL zihlukanisiwe. Ama-receptors e-LDL abuye abuyele ebusweni bamaseli wesibindi, lapho "angabamba" khona izinhlayiya ezingaphezulu ze-LDL.
I-PCSK9 iyi-protein elawulayo ebophezela nakwe-receptors ye-LDL. Ama-receptors e-LDL aphethwe yi-PCSK9 awaphindaphindiwe emuva esitokisini, kepha kunalokho aphukile ngaphakathi kweli cell.
Ngakho-ke, i-PCSK9 inciphisa ikhono lesibindi ukususa i-LDL cholesterol egazini legazi. Ngokuvimbela i-PCSK9, lezi zidakamizwa ezintsha zithuthukisa ngokuphumelelayo ikhono lesibindi lokususa i-cholesterol ye-LDL, nokunciphisa amazinga egazi le-LDL.
Uma i-PCSK9 inhibitor ingeziwe kumuthi ophezulu wezitho zomzimba, amazinga e-LDL ama-cholesterol aqhutshwa njalo ngaphansi kwe-50 mg / dL, futhi ngokuvamile afika ku-25 mg / dL noma ngaphansi.
I-PCSK9 Inhibitors
Ngesikhathi amaprotheni okulawula i-PCSK9 atholakala ekuqaleni kwawo-2000, ososayensi baqaphela ngokushesha ukuthi ukuvimbela le protheyini kufanele kubangele amazinga aphansi we-LDL cholesterol. Izinkampani ezidakamizwa zaqala ukugijimela emncintiswaneni ukuthuthukisa i-PCSK9 inhibitors.
Okumangalisa ukuthi lezi zidakamizwa sezivele zakhiwe futhi zivivinywa ekuvivinyweni komtholampilo: i-evolucumab (i-Repatha, eyenziwe ngu-Amgen) kanye ne-alirocumab (Okubalulekile, eyenziwe nguSanofi no-Regeneron). Zombili lezi zidakamizwa zingama -antibodies omzimba , oklanyelwe ukuba nomphumela kuphela ku-PCSK9, futhi (okungenani, okungenani) akukho ndawo. Zombili zilawulwa yi-injection subcutaneous (njenge-insulin therapy), futhi inikezwa kanye noma kabili ngenyanga.
Ukuhlolwa Kwemitholampilo Nge-PCSK9 Inhibitors
Izivivinyo zakuqala zasemtholampilo zenziwa nge-evolucumab (izilingo ze-OSLER) kanye ne-alirocumab (izilingo ze-ODYSSEY), ezenzelwe ukuhlola ukuphepha nokubekezela kwezidakamizwa ezintsha.
Kulezi zivivinyo, iziguli ezingaphezu kuka-4500 ezinamazinga e-cholesterol aye aboniswe kanzima ukuphatha zithole enye noma enye yalezi zidakamizwa. Iziguli zazingenakulinganiswa ukuthola i-PCSK9 inhibitor kanye nesidakamizwa se-statin, noma isidakamizwa se- statin yedwa. Qaphela ukuthi akekho iziguli eziphathwa kuphela nge-PCSK9 inhibitor.
Bonke abahlanganyeli bokufunda bathola ama-statins.
Imiphumela kuzo zonke lezi zivivinyo kwakuyi-cholesterol efana ne-LDL encishisiwe kwiziguli ezithola i-PCSK9 inhibitor ngamaphesenti angaba ngu-60, uma kuqhathaniswa namaqembu alawulayo aphathwe ngesimiso esisodwa. Lezi zivivinyo zakuqala aziklanyelwe ngokuqondile ukukala ukuthuthukiswa komphumela wezinhliziyo, kodwa imiphumela ehlonishweyo kubantu abangahleliwe ukuthola i-PCSK9 inhibitor ibheka ithemba.
Ngasekupheleni kuka-2016 isifundo se-GLAGOV sibonise ukuthi, kubantu abangu-968 abane- coronary artery disease (i-CAD) abangahle balandelwe ukwelashwa nge-evolocumab kanye nesimiso noma isimiso sodwa, labo abathola i-evolocumab bavame (ngokulinganiselwe) ukunciphisa amaphesenti angu-1 kwendwangu emiphakathini ye-atherosclerotic -umphumela omuhle kakhulu.
Icala lokuqala eliyinhloko elenzelwe ukuhlola imiphumela yomtholampilo kwi-inhibitor ye-PCSK9, isilingo se-FOURIER, sanyatheliswa ekuqaleni kuka-2017. Lesi sifundo esikhulu sabhalisa abantu abangaphezu kuka-27 000 abane-CAD, futhi baphinde bawasebenzisa ukuze bathole i-evolocumab kanye nesimo se-statin ngokuhambisana nesimiso esisodwa. Ngemuva kwesikhathi esilandelayo sokulandelela kwezinyanga ezingu-22, imiphumela yomtholampilo eqenjini le-evolocumab yayithuthukisiwe kakhulu kusuka kumbono wesibalo, nakuba yizinga elincane. Ngokuqondile, ingozi yokuhlaselwa yinhliziyo yancipha ngamaphesenti angu-1.5, ingozi yokudinga ukwelashwa okungahambi kahle futhi ngamaphesenti angu-1.5, futhi ingozi yokushaya isifo ngamaphesenti angu-0.4. Isibalo sokufa asizange sinciphise kakhulu. Nakuba kungenzeka ukuthi ubukhulu bomhlomulo wezokwelapha kuzokwenza ngcono ngezikhathi ezinde zokulandelela, ukubhala ngokucacile ukuthi yilokho okuzothatha iminyaka embalwa.
Imiphumela emibi Nge-PCSK9 Inhibitors
Ezifundweni zemitholampilo nge-PCSK9 inhibitors, iningi leziguli lalinemiphumela eminye emibi-ikakhulukazi ukusabela kwesikhumba endaweni yomjovo, kepha ukusabela okubi kwahlanganisa nokuhlukunyezwa komzimba (okufana nemiphumela emibi yemisipha yezinhlamba ) nezinkinga ze-neurocognitive (ngokuqondile, i-amnesia nokukhubazeka kwememori). Ezifundweni zokuqala lo mphumela wokugcina wesibonakaliso ubonwe cishe ngamaphesenti angu-1 weziguli okungahleliwe ku-PCSK9 inhibitor.
Isimo sezinkinga zengqondo , ngenkathi siphansi, sikhulise amafulegi okuxwayisa. Esifundweni esincane sesilingo se-FOURIER, kwakungekho ukuhlukana okuphawulekayo emsebenzini wokuzicabangela phakathi kwabantu abathola i-evolocumab kanye nesimiso, uma kuqhathaniswa nabantu abathola isitetim kuphela. Kodwa-ke, lo mbuzo uhlala ukuthi ngabe ukushayela kwamazinga e-cholesterol emazingeni aphansi kakhulu isikhathi eside kungandisa ingozi yokuncipha kwengqondo, kunoma yiziphi izidakamizwa ezisetshenziselwa ukwenza kanjalo. Kanti futhi, kudingeke ukuthi kulandelwe isikhathi esilandelayo ukuze uthole isibambiso esingcono kulo mbuzo obalulekile.
I-PCSK9 Inhibitors ku-Perspective
I-PCSK9 inhibitors ingase ibe yindlela enkulu ekupheni uketshezi lwe-cholesterol, nasekunciphiseni ingozi yomzimba. Kodwa-ke, naphezu kwayo yonke intshiseko evezwa yizinhliziyo eziningi, kufanele sigcine izinto ngendlela efanele manje.
Okokuqala , ngenkathi imiphumela yemisipha nemithi emisha ibonakala iphuthukisiwe kakhulu (ngezifundo ezincane zesikhashana), ubukhulu bokuthuthukiswa kuze kube manje akuyona enkulu kakhulu. Ukulandelwa kwesikhathi eside kuzodingeka ukuthi ubone ukuthi iningi lemithi likhiqiza kangakanani-futhi, ikakhulukazi, ukuthi ekugcineni lizokunikeza yini inzuzo yokufa yesikhathi eside.
Okwesibili , njengazo zonke izidakamizwa "zedizayidi" zanamuhla (izidakamizwa ezenzelwe isikhombimsebenzisi esithile), i-PCSK9 inhibitors yabiza kakhulu. Ukusetshenziswa kwabo, okungenani eminyakeni yokuqala, cishe kuzobekwa kuphela kubantu abasengozini enkulu, futhi ingozi yabo ayikwazi ukuncishiswa kakhulu ngezimiso-njengabantu abane- hypercholesterolemia yomndeni .
Okwesithathu , kuyilapho lezi zidakamizwa zikhulunywa ngokuthi zithatha esikhundleni se-statin therapy, kufanele siqaphele ngokucophelela ukuthi izilingo zomtholampilo kuze kube manje zizisebenzise ngaphezu kwezimo zomthetho, hhayi esikhundleni sesimiso. Ngakho-ke, empeleni asikho idatha yemitholampilo yokusitshela ukuthi ingabe ingaba yizikhundla ezifanelekayo zesimanje.
Okwesine , ngenkathi iphrofayli yokuphepha yezidakamizwa ze-PCSK9 kuze kube manje ibukeka ithembise, kukhona khona imibuzo evulekile; ikakhulukazi, ukuthi ngabe ukushayela i-cholesterol kumazinga aphansi kakhulu isikhathi eside kungase kube yinto encane engakwenzi, ikakhulukazi ngokuphathelene nokusebenza kwengqondo.
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