Ka hortagga PCSK9 ayaa muujinaya ballan, laakiin waxaan u baahanahay macluumaad badan oo dheeraad ah
Nooc cusub oo daawooyinka anti-cholesterol-ka horjoogayaasha PCSK9 - waxay abuurayaan waxyaalo badan oo kufilan bulshada dhexdeeda, iyo warbixino kala duwan ayaa soo jeedinaya daawooyinkan cusub inay noqon karaan kuwo aad u fiican oo loogu talagalay bukaanada ay ku adagtahay in ay qaataan dawooyinka . Labada ugu horreeya ee PCSK9-celiyeyaasha - Repatha (evolucumab) iyo Praluent (alirocumab) -waxaa loo ogolaaday isticmaalka sanadka 2015.
Daawooyinka ka hortagga PCSK9 waxay runtii u noqon kartaa horumar weyn oo ku dhacda kolestaroolka.
Si kastaba ha noqotee, nabadgelyadooda iyo waxtarkooda muddada dheer wali si buuxda looma dhicin. Taas, iyo kharashka aadka u sarreeya, ayaa ka baxaya dhakhaatiirta intooda badan ee aan weli hubin maanta oo ah meeshooda ku habboon ee daawada kiliinikada.
Sidee Shaqaalaha PCSK9 u Shaqeeyaa?
Daawooyinkani waxay xakameynayaan xakameynta kolesteroolka loo yaqaan "proprotein convertase subtilisin / kexin 9" (PCSK9) ee beerka. Dusha sare ee unugyada beerka waxaa ku jira xayawaanka LDL, oo isku xira qaybaha LDL ee wareegsanaya (oo ay ku jiraan LDL kolesterool ) oo ka saar dhiigga. Labada qaybood ee LDL iyo qabtayaasha LDL ayaa markaa loo wareejiyaa unugyada beerka, halkaas oo qaybaha LDL kala jaban yihiin. Receptors LDL ayaa markaa dib ugu soo noqda qaybta unugyada beerka, halkaas oo ay ku dabooli karaan "waxyeello" qaybo badan oo LDL ah.
PCSK9 waa borotiinka habraaca kaas oo sidoo kale ku xidhan dukaamada LDL. Qalabka LDL ee ku xiran PCSK9 dib looguma soo celiyo dusha qolka unugyada, laakiin halkii ayaa la jabiyaa gudaha gudaha.
Sidaa darteed, PCSK9 waxay xaddideysaa awoodda beerka si looga saaro kolestaroolka LDL ee dhiigga. By la xakameynayo PCSK9, daawooyinkan cusub waxay si waxtar leh u hagaajin karaan awoodda beerka ee looga saaro kolestaroolka LDL, oo lagu yareeyo heerarka dhiigga ee LDL.
Marka daawada PCSK9 lagu daro daaweynta qiyaasta daawada sare, daaweynta LDL kolesteroolka ayaa si joogta ah loola dhaqmaa 50 mg / dL, inta badanna 25 mg / dL ama ka yar.
Ka hortagga PCSK9
Markii la ogaado borotokoolka PCSK9 horaantii 2000, aqoonyahanadu waxay isla markiiba ogaadeen in xanibaadda borotiinkan ay tahay inay keento heerarka hoos loogu dhigo LDL kolesteroolka. Shirkadaha maan-dooriyeyaasha ayaa isla markiiba bilaabay tartan lagu hormarinayo xannibaadaha PCSK9.
Waxaa xusuus mudan, laba ka mid ah daawooyinkan ayaa horay loo sameeyay oo tijaabiyey tijaabooyinka kiliinikada: evolucumab (Repatha, oo ay soo saareen Amgen) iyo alirocumab (Praluent, oo ay samaysay Sanofi iyo Regeneron). Labada ka mid ah daawooyinkaasi waa unugyada difaaca , oo loogu talagalay in ay saameyn ku yeeshaan oo kaliya PCSK9, iyo (asal ahaan, ugu yaraan) meel kale oo kale. Waxay labaduba maamulaan cirbadaynta subcutanous (sida insulin terabi), waxaana la siiyaa mar ama laba jeer bishiiba.
Dhibaatooyinka Daawada Iyadoo La Xakameynayo PCSK9
Hawlgallada hore ee kiliinikada waxaa lagu sameeyay evolucumab (tijaabooyinka OSLER) iyo alirocumab (tijaabooyinka ODYSSEY), loogu talagalay in lagu qiimeeyo badbaadada iyo dulqaadashada daroogooyinka cusub.
Tijaabooyinkan, in ka badan 4500 oo bukaan ah kuwaas oo heerarka kolestaroolka ay adkeyd in lagu daaweeyo mid ama mid kale oo daroogooyinkaas ah. Bukaan-socodka ayaa loo kala soocay si loo helo mid ka mid ah PCSK9 inhibitor ah oo ay wehliyaan daroogada dawooyinka, ama daroogada gobolka oo kaliya. Ogsoonow in qof bukaanka ah loola dhaqmey oo keliya kaliya daaweynta PCSK9.
Dhamaan ka qaybgalayaasha daraasadu waxay heleen statins
Natiijooyinka dhammaan tijaabooyinkan waxay ahaayeen kuwo isku mid ah -LDL ayaa hoos u dhacay bukaanada qaadaya PCSK9 inhibitor boqolkiiba 60, marka la barbardhigo kooxo xakameysan oo lagu daweeyo statin oo keliya. Dacwadahan horay loogu talagalay looguma talagelin in lagu cabbiro hagaajinta natiijooyinka wadnaha, laakiin natiijooyinka la arkay ee dadka loo kala soocay si loo helo PCSK9 inhibitor ayaa u muuqday rajo.
Dabayaaqadii 2016-ka daraasadda GLAGOV ayaa muujisay, in 968 qof oo qaba cudurka loo yaqaan 'coronary artery (CAD)' oo loo kala soocay daaweynta 'evolocumab' iyo 'statin' ama 'statin' oo kali ah, kuwa qaata evolocumab khibrad ahaan (celcelis ahaan) 1% ee dabaqyada atherosclerotic - natiijo wanaagsan oo wanaagsan.
Diiwaanka ugu weyn ee loogu talagalay in lagu qiimeeyo natiijooyinka daaweynta PCSK9 inhibitor, FOURIER trial, ayaa la daabacay horraantii 2017. Daraasadan weyn ayaa ka diiwaangashan 27,000 qof oo leh CAD, waxayna mar kale u kala soocday si ay u qaataan evolocumab iyo statin oo ka soo jeeda dawlad kaliya. Ka dib markii celceliska dabagalka ah ee 22 bilood, natiijooyinka kiliinikada ee kooxda loo yaqaan "evolocumab" ayaa si weyn uga soo fiicnaaday qiyaasta tirakoobka, inkastoo ay tahay xadka ugu yar. Khaas ahaan, halista wadno-qabadka wadnaha ayaa hoos u dhacday boqolkiiba 1.5, khatarta ah in loo baahdo daweynta daweynta ee loo yaqaan 'invasive therapy therapy' sidoo kale 1.5 boqolkiiba, iyo khatarta istaroogga ee 0.4%. Xaaladda dhimashada lama yareeyn. Inkastoo ay u badan tahay in miisaanka gargaarka bukaan socodka uu sii wanaajin doono waqtiyada xiga ee dheeraadka ah, oo caddaynaya xaqiiqda ah in kiisku qaadan doono dhowr sano oo dheeraad ah.
Saameynnada Waxyeellada leh ee Kaararka PCSK9
Daraasaadka kiliiniga ee ka hortagga PCSK9, badankood bukaanku waxa ay qabaan waxyeellooyinka qaarkood-badanaa falcelinta maqaarka goobta cirbadda, laakiin ficilcelin xun ayaa sidoo kale ka mid ah murqaha xanuunka (oo la mid ah dhibaatooyinka muruqa ee duruufaha statins ) iyo dhibaatooyinka maskaxda (gaar ahaan, amnesia iyo maqnaanshaha xusuusta). Daraasadaha ugu horeeya ee saameyntaan dambe ayaa lagu arkay qiyaastii boqolkiiba hal bukaan oo loo qoondeeyey PCSK9 inhibitor ah.
Xaaladda dhibaatooyinka garashada , halka hooseeya, ayaa kor u qaaday calamadaha digniinta ah. Daraasad hoose oo ku saabsan tijaabada FOURIER, ma jirin faraqyo muhiim u ah shaqeynta garashada ee u dhaxaysa dadka qaata evolocumab iyo plus, marka loo barbar dhigo dadka hela statin oo keliya. Si kastaba ha noqotee, su'aashu waxay ku saabsantahay haddii heerarka kolestaroolka ee heerarka aad u hooseeya muddo dheer uu kordhin karo khatarta garashada garashada, daroogo kasta oo loo isticmaalo in la sameeyo. Mar labaad, dabagal dheeraad ah ayaa loo baahan yahay si loo helo hab wanaagsan oo ku saabsan su'aashan muhiimka ah.
PCSK9 Joojiya Ka-hortagga
Ka hortagga PCSK9 ayaa dhab ahaantii u muuqda inay noqdaan tallaabo weyn oo lagu daaweynayo kolestaroolka, iyo yareynta halista wadnaha. Si kasta ha ahaatee, inkastoo dhammaan xiisaha ay muujiyeen dhakhaatiir badan oo wadnaha ah, waa in aynnu wax ka qabanno hadda.
Ugu horreyn , halka natiijooyinka wadnaha iyo daawooyinka cusubi ay u muuqdaan kuwo si weyn u fiicnaaday (barashada mudada gaaban), miisaankii horumarinta ilaa hadda ma aha mid aad u ballaaran. Kormeer joogto ah ayaa lagama maarmaan u ah inay si dhab ah u eegaan inta faa'iido badan ee daawooyinkan soo saaraan- iyo, gaar ahaan, inay ugu dambeyntii bixin doonaan lacagta dhimashada muddada dheer.
Marka labaad , sida dhammaan "mukhaadaraadka naqshadeeye" (daawooyinka lagu magacaabo qeexitaanka qaaska ah ee loo yaqaan molecular target), PCSK9 celiyeyaasha waa kuwo aad u qaali ah. Isticmaalkooda, ugu yaraan sanadaha hore, waxay ku dhowdahay inay ku koobnaadaan dadka khatarta aadka u sareysa, khatartaasna aysan hoos u dhigi karin sheyga-sida dadka qaba hypercholesterolemia .
Saddexaad , inkastoo daroogooyinkaas loo la 'yahay sidii loo beddeli lahaa daweynta daweynta statin, waa inaan si taxadar leh u fiirsanaa in tijaabooyinka kiliinikada ilaa taariikhda ay isticmaalaan iyaga marka loo eego mawqifka, oo aan loo beddelin sheyga. Sidaa darteed, dhab ahaantii ma hayno macluumaad xogeed oo aan noo sheegno haddii ay noqon karaan kuwo beddeli kara beddelka statin.
Qodobka afaraad , halka feejignaanta nabadgelyada ee daroogada PCSK9 illaa iyo hadda u muuqato rajo, weli waxaa jira su'aalo furan; gaar ahaan, haddii loo raaco in kolestaroolka daruuriga ah ee heerarka hooseeya ee muddo dheer uu soo noqon karo ugu yaraan qayb ahaan wax-soo-saarka, gaar ahaan marka la eego hawlaha garashada.
> Ilo:
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> Robinson JG, Farnier M, Krempf M, iyo al. Waxtarka iyo Ammaanka Alirocumab ee Yareynta Dareemaha iyo Dhacdooyinka Wadnaha. N Engl J Med 2015; DOI: 10.1056 / NEJMoa501031.
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