Masu haɗin PCSK9 sun nuna alkawuran, amma muna bukatar mai yawa bayanai
Wani sabon bangarori na maganin cholesterol-masu hana PCSK9-yana samar da ƙwararriyar yawa a cikin al'umma, kuma rahotanni daban-daban sun bada shawarar cewa wadannan sababbin kwayoyi na iya zama babban matsala ga marasa lafiya waɗanda ke da matsala wajen ɗaukar kwayoyin . An kwantar da masu hanawa guda biyu na PCSK9-Repatha (evolucumab) da Praluent (alirocumab) don amfani a shekarar 2015.
Kwayoyin maganin PCSK9 na iya zama babban mahimmanci a cholesterol-downering.
Duk da haka, ba'a tabbatar da aminci da tasiri na tsawon lokaci ba. Hakanan, da kuma kudin da suke da ita, yafi yawancin likitoci ba su da tabbacin yau game da wurin da suke dacewa a magani.
Yaya Masu Shirye-shiryen PCSK9 suke aiki?
Wadannan kwayoyi sun hana mai kula da cholesterol da ake kira "proprotein convertase subtilisin / kexin 9" (PCSK9) a cikin hanta. Ginin ɗadun hanta sun ƙunshi masu karɓa na LDL, wanda ke ɗaura yana rarraba ƙwayoyin LDL (wanda ya ƙunshi LDL cholesterol ) kuma ya cire su daga jini. Dukkanin sunadaran LDL da masu karɓar LDL sun koma cikin kwayoyin hanta, inda aka rabu da ƙananan LDL. Masu karɓar LDL sannan su koma cikin farfajiyar hanta, inda zasu iya "tarkon" karin ƙwayoyin LDL.
PCSK9 tsarin gina jiki ne wanda ke haɗawa ga masu karɓar LDL. LDL masu karɓa da PCSK9 ke ɗauka ba su sake komawa zuwa tantanin halitta ba, amma a maimakon haka an rushe cikin tantanin halitta.
Saboda haka, PCSK9 tana iyakar hanta don cire LDL cholesterol daga jini. Ta hanyar hana PCSK9, waɗannan sababbin kwayoyi sun inganta karfin hanta don cire LDL cholesterol, kuma rage matakan LDL.
Yayin da aka kara magungunan PCSK9 zuwa likitan maganin statin, LDL cholesterol matakan da aka kaddamar da shi a ƙasa da 50 MG / dL, sau da yawa zuwa 25 MG / DL ko žasa.
Masu hana PCSK9
Lokacin da aka gano tsarin gina PCSK9 a farkon shekarun 2000, masana kimiyya sun fahimci nan da nan cewa hana wannan sunadaran zai haifar da ƙananan matakan cholesterol LDL. Kamfanonin ƙwayoyi masu sauri sun kaddamar da wani tsere don ci gaba da hana masu hana PCSK9.
Abin mamaki dai, an riga an ci gaba da amfani da kwayoyi biyu daga cikin gwajin gwagwarmaya: evolucumab (Repatha, Amgen) da kuma alirocumab (Praluent, Sanofi da Regeneron). Duk waɗannan kwayoyi sune kwayoyin cutar guda daya , an tsara su don samun sakamako kawai akan PCSK9, kuma (a cikin akalla) babu wani wuri. Dukkanin su suna yin amfani da allurar subcutaneous (kamar su insulin), kuma an ba su sau ɗaya ko sau biyu a wata.
Jarabawa na Clinical tare da Masu Cire PCSK9
An gudanar da gwaje-gwaje a farkon asibiti tare da evolucumab (gwajin OSLER) tare da samfurin kamfanoni (gwajin ODYSSEY), wanda aka tsara domin tantance lafiyar da jurewa da sababbin kwayoyi.
A cikin wadannan gwaje-gwajen, fiye da mutane 4500 marasa lafiya wanda ƙwayoyin cholesterol sun tabbatar da wuya a bi da ɗaya ko daya daga cikin wadannan kwayoyi. An ba da marasa lafiya asali don karɓar ko dai wani mai hanawa na PCSK9 tare da magungunan statin, ko magani na statin kadai. Ka lura cewa babu marasa lafiya da aka kula da su kawai tare da mai hana PCSK9.
Dukkan masu nazarin da aka samu sun karbi statins.
Sakamakon duk wadannan gwaje-gwajen sun kasance kamar-LDL cholesterol ya rage a marasa lafiya da ke karɓar mai hanawa PCSK9 ta kimanin kashi 60 cikin dari, idan aka kwatanta da ƙungiyoyi masu kula da su da wani statin kadai. Wadannan gwaje-gwaje na farko ba a ƙayyade su ba don auna fasali a sakamakon cututtuka na zuciya, amma sakamakon da aka samu a cikin mutane wanda ba'a samu ba don karɓar mai kula da PCSK9 ya gamsu.
A ƙarshen shekara ta 2016, binciken GLAGOV ya nuna cewa, a cikin mutane 968 da cututtukan cututtuka (CAD) waɗanda aka bazu su zuwa magani tare da ko evolocumab da statin ko statin kadai, waɗanda ke karɓar evolocumab sun kamu (kashi) kashi 1 cikin dari na girman na alamarsu na atherosclerotic - wani sakamako mai kyau.
Na farko babban gwajin da aka tsara don kimanta sakamakon binciken asibiti a kan wani mai hana PCSK9, jarrabawar FOURIER, an wallafa shi a farkon 2017. Wannan babban binciken ya ƙunshi fiye da mutane 27,000 tare da CAD, kuma ya sake ba su damar karɓar evolocumab da statin da wani statin kadai. Bayan wani lokaci mai zuwa na watanni 22, an samu sakamako mai mahimmanci a cikin ƙungiyar evolocumab daga matsayin da aka yi a lissafi, kodayake kawai a matsakaici. Musamman, haɗarin ciwon zuciya ya ragu da kashi 1.5 cikin 100, haɗarin da ake bukata na farfadowa na likita kuma kashi 1.5 cikin dari, kuma hadarin fashewa ta kashi 0.4. Ba a rage mawuyacin yanayin mutuwa ba. Duk da yake akwai yiwuwar ƙarfin amfanar asibiti zai inganta tare da tsawon lokaci na biyo baya, yin bayanin cewa tabbas lamarin zai faru a wasu 'yan shekaru.
Hanyoyi na gefen tare da masu hana PCSK9
A cikin binciken binciken asibiti tare da masu cin zarafi na PCSK9, yawancin marasa lafiya sunyi komai wasu sakamako masu illa-musamman halayen fata a wurin ginin, amma mummunan halayen sun hada da ciwon tsoka (kamar tsoffin cututtukan tsoka na statins ) da matsalolin neurocognitive (musamman, amnesia da ƙuntatawar ƙwaƙwalwa). A cikin binciken farko an gano wannan sakamako na karshe a kimanin kashi 1 cikin dari na marasa lafiya da aka bazu a wani mai hana PCSK9.
Halin da ake ciki na matsalolin halayen , yayin da ƙananan, ya tada wasu takardun gargaɗin. A cikin binciken da aka yi na jarrabawar FOURIER, babu wani bambanci da ke tsakanin aiki tsakanin masu karɓar evolocumab da statin, idan aka kwatanta da mutanen da suka karbi statin kadai. Duk da haka, wannan tambayar ya kasance ko yin aiki da ƙwayar cholesterol zuwa matakan ƙananan matakai na tsawon lokaci zai iya ƙara haɗarin ƙin yarda, duk abin da ake amfani da kwayoyi don yin haka. Bugu da kari, ana buƙatar tsawon lokaci don biyan bukatun wannan tambaya mai muhimmanci.
PCSK9 Masu hanawa a hangen nesa
Ma'aikatan PCSK9 na iya haifar da babbar nasara wajen magance cholesterol, da kuma rage cututtukan zuciya. Duk da haka, duk da sha'awar da mutane da yawa ke nunawa, ya kamata mu ci gaba da kasancewa a hankalinsu a yanzu.
Na farko , yayin da magungunan cututtukan zuciya tare da sababbin kwayoyin sun fara ingantawa sosai (a cikin gajeren binciken karatu na gajeren lokaci), girman girman ci gaba har zuwa yanzu bai kasance ba. Tsarin lokaci mai tsawo zai zama wajibi don ganin yadda yawancin kwayoyi suke samarwa-kuma, musamman, ko za su samar da amfani ga mace-mace mai tsawo.
Na biyu , kamar dukkanin '' masu magunguna '' zamani '' (magungunan da aka sanya don ƙirar kwayoyin halitta), masu sarrafawa PCSK9 suna da tsada sosai. Amfani da su, a kalla a cikin shekaru na farko, za a kusan iyakance su ga mutanen da ke cikin haɗari, kuma ba za a iya rage haɗarin su tare da statins-kamar su mutane da ke da hypercholesterolemia na iyali .
Na uku , yayin da ake magana da wadannan kwayoyi a madadin tsarin farfadowa na statin, ya kamata mu lura da hankali cewa jarrabawar gwaje-gwaje a yau sun yi amfani da su banda statins, kuma ba maimakon statins ba. Saboda haka, ba mu da wani bayani na asibiti don gaya mana ko za su iya kasancewa su zama masu maye gurbin daji.
Hudu , yayin da bayanin lafiyar kamfanonin PCSK9 ya zuwa yanzu yana da alamar alkawarin, akwai tambayoyi masu yawa; musamman ma, game da korawar cholesterol zuwa ƙananan matakan na tsawon lokaci zai iya zama abin ƙyama a wani ɓangare, musamman ma game da aikin haɓaka.
> Sources:
> Nicholls SJ, Puri R, Anderson T, et al. Hanyoyin Evolocumab akan Ci gaba na Cututtukan Lafiya a cikin marasa lafiya na Statin-treated. GLAGOV Ƙaddamarwa na Clinical Testing. JAMA 2016. DOI: 10.1001 / jama.2016.16951
> Robinson JG, Farnier M, Krempf M, et al. Aminci da Tsaro na Alirocumab a Rage Rashin Lafiya da Zaman Lafiya. N Engl J Med 2015; DOI: 10.1056 / NEJMOA501031.
> Sabatine MS, Giugliano RP, Keech AC, et al. Ayyukan Evolocumab da Ciwon Bidiyo na Ƙwararrun marasa lafiya da cututtukan zuciya. N Engl J Med 2017; DOI: 10.1056 / NEJMoa1615664.
> Sabatine MS, Guigliano RP, Wiviott SD, et al. Aminci da Tsaro na Evolocumab a rage Rashin Lafiya da Zaman Lafiya. N Engl J Med 2015; DOI: 10.1056 / NEJMOA1500858.
> Stone NJ, Lloyd-Jones DM. Rawancin LDL Cholesterol yana da kyau, amma ta yaya kuma a wa? N Engl J Med 2015; DOI: 10.1056 / NEJM1502192.