Ezinye izazi ze-cardiologists ziyahamba ngezigaba ezintsha zemithi ye-cholesterol.
E-American College of Cardiology sika (ACC's) Scientific Session Yonyaka eyayihlala edolobheni laseSan Diego phakathi no-Mashi 2015, umoya wawunzima ngokukhuluma ngama-PCSK9 inhibitors. Ngokuqondile, izazi ze-cardiologist eziningi ezazikhona zazithuthukisa kakhulu imiphumela yokuhlolwa konyaka okwase- Amgen's Repatha (evolocumab) . Ezilingo zomtholampilo, i-PCSK9 inhibitors njenge-evolocumab ne-Regeneron / Sanofi's Value (alirocumab) iye yaboniswa ukunciphisa i-LDL-C ("okubi" ye-cholesterol) okungenani kakhulu njengezithombeni futhi mhlawumbe ngaphezulu .
( Izitatimende ziyimithi efana neZocor neCrestor.
Ekugcineni, ukwehlisa amazinga e-LDL ama-cholesterol nje kuphela ukuwanciphisa kungabanikeza inzuzo yangempela ngaphandle kokunciphisa ingozi yemicimbi yezinhliziyo ezinjenge-stroke ne-heart attack. Futhi ukuze sibone ukuthi inzuzo enjalo yokuvikela isikhathi eside ikhona, sidinga ukutadisha isikhathi eside ... iminyaka emide kunokukhuthazayo, nokho, imiphumela yonyaka owodwa esiwufakazayo njengamanje.
Yini i-PCSK9 inhibitors?
I-proprotein convertase subtilisin / i-Kexin uhlobo 9 noma i-PCSK9 isakhi sofuzo esibamba iqhaza ku-cholesterol kanye ne-fatty acid metabolism. Abantu abanezinhlobo ezihlukahlukene ezingavamile zofuzo ze-PCSK9 babhekwa njengamazinga e-LDL-C ("ama-cholesterol" amabi) afana nalawo asezingeni elilinganiselayo. Ngaphezu kwalokho, ukushintshashintsha kwezakhi zofuzo kuye kwaxhunyaniswa ne-autosomal hypercholesterolemia , eyisifo esiyingozi esibangela amazinga aphezulu kakhulu we-lipids noma i-cholesterol nesifo senhliziyo.
Ngenxa yokubheka okunjalo, izinkampani zezidakamizwa u-Amgen no-Regeneron / Sanofi ziye zakha amakhomikhali e-monoclonal aqondisa amaprotheni we-PCSK9 (okubhalwe yi-PCSK9 gene): Ukuphindaphinda nokulinganisa ngokulandelana.
Imiphumela Emva Konyaka owodwa (ish) weTherapy Ne-PCSK9 Inhibitors
Ngo-Mashi 17, 2015, I-New England Journal of Medicine yanyathelisa amaphepha amabili afaka imiphumela yamaviki angu-52 kusuka ku-evolocumab's OSLER-1 no-OSLER-2 ukuhlolwa kanye nemiphumela engu-78 yamasonto angu-Reneral Regeneron / Sanofi's ODYSSEY.
Eminye imiphumela ebalulekile evela kuhlolo lwe-OSLER ifaka okulandelayo:
- Ngamaviki ama-48 wezokwelapha, i-evolocumab yaqhubeka nokunciphisa amazinga e-LDL-C ngamaphesenti angu-61 kwabahlanganyeli abanamazinga ahlukahlukene ezinengozi zomzimba.
- Ngamaviki angu-52 wezokwelapha, izinga lezenzakalo ze-cardiovascular (ukushaya kwenhliziyo, isifo sohlangothi, i- TIA njalonjalo) kwakungamaphesenti angu-2,18 kulabo ababambe iqhaza abangathathi i-evolocumab kodwa emithini yokwelashwa engokwemvelo ejwayelekile (ukuthatha izitembu) uma kuqhathaniswa namaphesenti angu-0.95 kulabo abathatha i-evolocumab kanye ne-standard-care-carerapy therapy (ukuthatha iziqu).
- Izenzakalo ezimbi ze-neurocognitive kanye nemiphumela emibi engeyona embi ehlanganisa i-arthralgia, ikhanda lokuhlukunyezwa, ubuhlungu besilungu nokukhathala kwabikwa kaningi kubahlanganyeli abathatha i-evolocumab.
Eminye imiphumela ebalulekile evela ekulingweni kwe-ODYSSEY ihlanganisa okulandelayo:
- Ngamaviki angu-78 wezokwelapha, i-alirocumab inciphisa amazinga e-LDL-C ngamaphesenti angaba ngu-60 kubo bonke ababambiqhaza kubandakanya iziguli ezinobungozi obukhulu (labo abane-hypercholesterolemia yomndeni noma izici eziningi ezingozini zomzimba ezifana nokubhema, isifo sikashukela nokunye).
- Imiphumela emibi ekhishwa ukwelashwa nge-alirocumab ihlanganisa ukuphendula komjovo-site, i-myalgia, izenzakalo ze-neurocognitive ne-ophthalmologic.
- Zonke iziguli kulolu cwaningo zase zisesimweni esisezingeni eliphakeme-noma isilinganiso sezinga eliphezulu noma isilinganiso esiphezulu sokubekezela. Ezigulini ezithola i-alirocumab, izinga lemicimbi ye-cardiovascular kwaba amaphesenti angu-1.7 kanye no-3.3% kulabo abathatha indawo.
Ingabe i-PCSK9 Inhibitors izitatimende ezintsha?
I-cardiologists manje isibuza isimo se-cholesterol njenge-biomarker yokuphela. Njengoba sifundile ekucwaningeni kwangaphambilini, ezinye izidakamizwa ezinciphisa i-LDL-C, ukwandisa i-HDL nokunye angeke zinikeze inzuzo yezwe langempela njengokuvimbela isifo noma ukuhlasela kwenhliziyo. Indlela i-cholesterol ne-lipids esebenzelana ngayo emzimbeni wethu iyinkimbinkimbi kunalokho esiyiqonda njengamanje.
Ngakolunye uhlangothi, ukhetho olungcono kakhulu esinalo lokuphatha izifo zenhliziyo yiziphathamandla, iklasi elidakamizwa eliyingqayizivele elivimbela izenzakalo zekusasa zenhliziyo. Lezi zidakamizwa mhlawumbe zisebenza ngokungagcini nje kuphela ukwehlisa amazinga e-LDL kodwa nangokuqinisa izikhala ezivala imishanguzo yethu.
Ukuze i-PCSK9 inhibitors ibhekwe njengento ewusizo njenge-statins, sidinga iminyaka eminingana yemiphumela, yingakho u-Amgen okwamanje ehlanganisa isifundo se-FOURIER. Ucwaningo lwe-FOURIER luzohlolwa iminyaka emihlanu yokuphathwa kwe-evolocumab kulabo abathatha izitembu kanye nengozi ephezulu yemicimbi ye-cardiovascular like stroke and heart attack. (Uma unesithakazelo, okwamanje i-AMGEN inxusa abahlanganyeli ekutadisheni.) Ngemiphumela evela ku-FOURIER isifundo, abacwaningi banethemba lokunciphisa ukwehla kwezigameko zenhliziyo ezibhekene nonyaka owodwa. Ngaphezu kwalokho, imiphumela yocwaningo ingasisiza ukuba siqonde kangcono ukuthi iziphi iziguli ezizuzwa kakhulu ezivela ku-PCSK9 inhibitors.
Eminyakeni embalwa, uma sibona inzuzo yesikhathi eside yesikhumba senhliziyo, singase sibheke impumelelo efana nesimo se-Amgen, umenzi we-evolocumab. Impumelelo enjalo inemibandela ngoba ngaphezu kokungaqiniseki ukuthi iziphi iziguli ezizokwazi ukuzuza kakhulu ku-evolocumab, kukhona okukodwa okukhathazayo mayelana ne-PCSK9 inhibitor: Ucwaningo lubonisa ukuthi kwabanye abantu, i-evolocumab kanye ne-alirocumab bangadla isistimu yesimiso esiyinhloko. Ngokuqondile, isilingo se-ODYSSEY siphakamise ukuthi i-alirocumab ingase ilahle imemori ngandlela-thile, ibangele i-amnesia noma ibangele ukudideka.
Imithombo
Isihloko esithi "i-PCSK9 inhibition kwiziguli ezine-hypercholesterolemia" yi-NR Desai kanye ne-MS Sabatine evela ku-Elsevier ngo-2015. Ukutholakala kusuka ku-Clinical Key ngomhla ka-3/15/2015.
Isihloko esithi "Ukusebenza Nokuphepha kwe-Alirocumab ekunciphiseni i-lipids nezenzakalo ze-Cardiovascular" nguJG Robinson nabalobi ababambisene nabo kusukela ku- NEJM 3/17/2015. Ifinyelele ngomhla ka-3/15/2015.
Isihloko esithi "Ukusebenza Nokuphepha kwe-Evolocumab ekunciphiseni i-Lipids nezenzakalo ze-cardiovascular" yi-MS Sabatine kanye nabalobi ababambisene nabo kusukela ku- NEJM 3/17/2015. Ifinyelele ngomhla ka-3/15/2015.
Isihloko esithi "Ukunciphisa I-Cholesterol LDL Kuhle, Kodwa Kanjani Futhi Kukabani?" ngoJean Stone no-DML James kusukela ku- NEJM 3/17/2015.