Akatswiri ena a mtima akupita kuchipatala kwa mankhwala atsopano a cholesterol.
Ku American College of Cardiology's (ACC's) Msonkhano Wakale wa Scientific womwe unachitikira mumzinda wa San Diego pakatikati pa mwezi wa March 2015, mpweya unali wolemetsa ndi kulankhula za PCSK9. Mwapadera, akatswiri a cardiologist ambiri omwe analipo ankalimbikitsidwa kwambiri ndi zotsatira za mayesero omwe akhala akuchitika kwa zaka zambiri pa Amgen's Repatha (evolocumab) . M'mayesero amachilombo, PCSK9 zowononga monga evolocumab ndi Regeneron / Sanofi's Primitive (alirocumab) zasonyezedwa kuti achepetse LDL-C (choipa "choipa") choposa ma statins komanso mwinamwake .
( Statins ndi mankhwala monga Zocor ndi Crestor.
Potsirizira pake, kungochepetsa khungu la kolesterolini LDL kuchepetsa iwo sangapindulitse phindu lenileni komanso kuchepetsa chiopsezo chakumbuyo kwa mtima monga matenda a stroke ndi matenda a mtima. Ndipo kuti tidziwe ngati phindu lachitetezo chotereli liripo, tikusowa phunziro la nthawi yaitali ... zaka zambiri kuposa zolimbikitsana, komabe, zotsatira za chaka chimodzi zomwe ife tirikuchitira umboni panopa.
Kodi PCSK9 inhibitors ndi chiyani?
Proprotein kusinthira subtilisin / Kexin mtundu 9 kapena PCSK9 ndi jini lomwe limathandiza mu cholesterol ndi mafuta amchere a shuga. Anthu omwe ali ndi mitundu yosawerengeka ya ma PCSK9 amawonedwa ngati ali ndi magulu a LDL-C ("choipa" cholesterol) chofanana ndi omwe ali ndi zizindikiro zolimbitsa thupi. Kuwonjezera pamenepo, kusintha kwa geni kwagwirizanitsidwa ndi matenda oopsa omwe amachititsa kuti pakhale matenda oopsa omwe amachititsa kuti munthu akhale ndi vuto la lipids kapena cholesterol komanso matenda a mtima.
Malingana ndi zochitika zoterezi, makampani osokoneza bongo Amgen ndi Regeneron / Sanofi apanga mapuloteni a monoclonal omwe amawunikira mapuloteni a PCSK9 (omwe amalembedwa ndi PCSK9 gene): Repatha ndi ofunika motsatira.
Zotsatira Zaka Zaka chimodzi (ish) za mankhwala ndi PCSK9 Zizindikiro
Pa March 17, 2015, The New England Journal of Medicine inasindikiza mapepala awiri ofotokoza zotsatira za masabata 52 kuchokera ku mayeso a evolocumab a OSLER-1 ndi OSLER-2 ndi zotsatira za sabata 78 kuchokera ku mayesero a Regeneron / Sanofi a ODYSSEY.
Zotsatira zina zofunika kuchokera ku mayesero a OSLER ndi awa:
- Kupyolera masabata 48 a mankhwala, evolocumab inachepetsa kuchepetsa kwa ma LDL-C ndi 61 peresenti mwa ophunzira omwe ali ndi misinkhu yosiyanasiyana ya matenda a mtima.
- Kupyolera masabata makumi asanu ndi awiri (52) a mankhwala, mlingo wa zochitika za mtima (matenda a mtima, kupwetekedwa mtima, TIA ndi zina zotero) zinali 2,18 peresenti mwa omwe sagwiritsa ntchito evolocumab koma pamasewero olimbitsa thupi (kutenga statins) poyerekeza ndi 0.95% evolocumab komanso pazifukwa zosamalidwa (kutenga statins).
- Zochitika zovuta zokhudzana ndi matenda osokoneza bongo pamodzi ndi zotsatira zosafunikira kwenikweni kuphatikizapo arthralgia, kupweteka mutu, kupweteka kwa miyendo, ndi kutopa zinafotokozedwa mobwerezabwereza mwa ophunzira kutenga evolocumab.
Zotsatira zina zofunika kuchokera ku mayesero a ODYSSEY ndi awa:
- Kupyolera masabata 78 a mankhwala, alirocumab inachepetsedwa m'misinkhu ya LDL-C ndi pafupifupi 60 peresenti ya anthu onse omwe ali ndi chiopsezo chachikulu (omwe ali ndi matenda a hypercholesterolemia kapena matenda ambiri a mtima monga kusuta, shuga ndi zina zotere).
- Zovuta zomwe zimayambitsidwa ndi mankhwala omwe alirocumab amaphatikizidwapo ndi machitidwe a jekeseni, myalgia, zochitika zamaganizo ndi zochitika za ophthalmologic.
- Odwala onse mu phunziroli anali kale kalembedwe-kaya mlingo wapamwamba kapena mlingo wokhazikika. Odwala omwe amalandira alirocumab, mlingo wa zochitika za mtima ndi 1,7 peresenti ndi 3.3 peresenti mwa iwo omwe amapanga placebo.
Kodi PCSK9 Inhibitors ndi New Statins?
Akatswiri a zamankhwala tsopano akukayikira kuti cholesterol ndi chikhalidwe chokha. Monga taphunzira kuchokera ku kafukufuku wammbuyo, mankhwala ena omwe amachepetsa LDL-C, kuonjezera HDL ndi zina zotero sangapereke ubwino weniweni wa dziko monga kupewa matenda a stroke kapena matenda a mtima. Momwe cholesterol ndi lipids zimagwirira ntchito mu thupi lathu ndi zovuta kwambiri kuposa momwe ife tikuzimvera panopa.
Ndipotu, njira yabwino kwambiri yothandizira matenda a mtima ndi statins, gulu lapadera la mankhwala lomwe limateteza zochitika zamtsogolo za mtima. Mankhwalawa mwina amagwira ntchito osati kungochepetsa ma LDL komanso kukhazikitsa zigawo zomwe zimatsegula mitsempha yathu.
Kuti PCSK9 inhibitors ziwoneke ngati zothandiza monga statins, tikufunikira zaka zingapo za zotsatira, chifukwa chake Amgen akusonkhanitsa phunziro la FOURIER. Kuphunzira kwa FOURIER kudzakhala kafukufuku wa zaka zisanu za kayendetsedwe ka evolocumab mwa iwo omwe amatenga zilembo komanso paziopsezo za zochitika za mtima monga matenda a stroke ndi matenda a mtima. (Ngati mukufuna, AMGEN pakali pano ikupempha ophunzira kuti aphunzire.) Chifukwa cha zotsatira za kafukufuku wa FOURIER, ofufuza akuyembekeza kuwonjezera kuchepa kwa zochitika za mtima zomwe zimachitika chaka chimodzi mpaka zaka zingapo . Komanso, zotsatira za phunziroli zingatithandize kumvetsetsa bwino lomwe anthu omwe ali odwala amapindula kwambiri ndi PCSK9.
Zaka zingapo, ngati tikuwona kupindula kwa mtima kwa nthawi yaitali, ndiye kuti tikhoza kuyang'ana bwino ngati Amgen, wopanga evolocumab. Kupambana koteroko ndizofunikira chifukwa pokhapokha osadziwa kuti anthu odwala angapindule bwanji ndi evolocumab, palinso chinthu chovuta kwambiri chokhudza PCSK9 inhibitor: Kafukufuku akusonyeza kuti mwa anthu ena, evolocumab ndi alirocumab zingasokoneze ndi dongosolo lalikulu la mitsempha. Kwenikweni, mayesero a ODYSSEY amasonyeza kuti alirocumab mwina imadetsa nkhawa, chifukwa cha amnesia kapena kusokoneza.
Zotsatira
Mutu wotchedwa "PCSK9 kulepheretsa odwala omwe ali ndi hypercholesterolemia" ndi NR Desai ndi MS Sabatine kuchokera ku Elsevier mu 2015. Opezeka ku Clinical Key pa 3/15/2015.
Mutu wotchedwa "Efficacy and Safety of Alirocumab mu Kuchepetsa Lipids ndi Zochitika Zokhudza Mtima" ndi JG Robinson ndi alembi ena a NEJM 3/17/2015. Idapezeka pa 3/15/2015.
Nkhani yotchedwa "Efficacy and Safety of Evolocumab mu Kuchepetsa Lipids ndi Zochitika Zachimtima" za MS Sabatine ndi alembi olemba kuchokera ku NEJM 3/17/2015. Idapezeka pa 3/15/2015.
Nkhani yotchedwa "Kuthetsa LDL Cholesterol Ndi Yabwino, Koma Nanga Ndi Ndani?" ndi NJ Stone ndi DML James kuchokera ku NEJM 3/17/2015.