PCSK9 inhibitors inoratidza chivimbiso, asi tinoda zvakawanda zvakawanda
Kirasi itsva yevanopesana ne-cholesterol zvinodhaka-iyo PCSK9 inhibitors-iri kuumba huwandu huzhinji mukati memharaunda yevanhu, uye mimwe mitauro inoratidza kuti mishonga iyi mitsva inogona kunge iri nzira yakakura kune varwere vane dambudziko rekutora mazita. Iviri yekutanga PCSK9 inhibitors-Repatha (evolucumab) uye Yakakosha (alirocumab) -kubvumidzwa kushandiswa muna 2015.
Iyo PCSK9 inhibitor zvinodhaka zvingangodaro inomiririra kukanganisa kukuru mukutora-cholesterol.
Kunyange zvakadaro, kuchengetedza kwavo kwenguva refu uye kubudirira hakukwanisi kusimbiswa. Izvo, uye mari yavo yakakwirira kwazvo, inosiya vakawanda vanachiremba vachiri nechokwadi nhasi nhasi munzvimbo yavo yakakodzera mumishonga yemakiriniki.
Ko PCSK9 Inhibitors Inoshanda Sei?
Iyi mishonga inovhara cholesterol mutongi anonzi "proprotein convertase subtilisin / kexin 9" (PCSK9) muropa. Pasi pemasero eropa ane LDL receptors, iyo inosunga kuparadzanisa LDL particles (iyo ine LDL cholesterol ) uye inoabvisa kubva muropa. Zvose zviri zviviri zvinonzi LDL uye zvinonzi LDL receptors zvino zvinoshandiswa kupinda mumasero eropa, umo LDL zvikamu zvinoparadzaniswa. I-LDL receptors inodzokera kumusoro kwemasero eropa, kwavanogona "kusunga" mamwe LDL particles.
PCSK9 ipuroteni yekuraira iyo inosungawo kune LDL receptors. LDL receptors yakasungwa neCCSK9 haidzokeri zvakare kumasero, asi pane iyo yakaputsika mukati memusero.
Saka, PCSK9 inogadzirisa kukwanisa kwechiropa kubvisa LDL cholesterol kubva muropa. Nokudzivisa PCSK9, mishonga iyi mitsva inobudirira inovandudza kukwanisa kwechiropa kubvisa LDL cholesterol, uye kuderedza mazinga eropa reLDL.
Apo PCSK9 inhibitor inowedzerwa ku-high-dose statin therapy, LDL cholesterol mazinga anowanzotungamirirwa pasi pe 50 mg / dL, uye kazhinji kusvika 25 mg / dL kana pasi.
The PCSK9 Inhibitors
Apo PCSK9 puroteni yakagadziriswa yakawanikwa mukutanga kwema2000, masayendisiti akabva aziva kuti kuvhara mapuroteni aya kunokonzera kuderedzwa kwakaderedzwa kweLDL cholesterol mazinga. Makambani ekushandisa zvinodhaka akabva atanga kupinda munhangemutange kukura PCSK9 inhibitors.
Zvinoshamisa, mbiri yemishonga iyi yakatosimbiswa uye yakaongororwa mumakiriniki: evolucumab (Repatha, yakagadzirwa naAmgen) uye alirocumab (Yakakosha, yakagadzirwa naSanofi uye Regeneron). Zvose izvi zvinodhaka zvinokonzerwa ne monoclonal antibodies , yakagadzirirwa kuva nemigumisiro chete paPCSK9, uye (inoretically, zvichida) hakuna imwe nzvimbo. Izvo zvose zvinotungamirirwa nejasi rejinga (sezvinoita insulin therapy), uye inopiwa kamwe chete kana kaviri pamwedzi.
Clinical Trials Na PCSK9 Inhibitors
Kuongororwa kwekliniki yekutanga kwakagadzirwa neevolucumab (miedzo ye OSLER) uye ne alirocumab (miedzo yeODYSSEY), yakagadzirirwa kuongorora kuchengetedza uye kushivirira kwemishonga iyi mitsva.
Mune miedzo iyi, vanopfuura 4500 varwere vane cholesterol maitiro avo vakaratidza kuti zvakaoma kurapa vakagamuchira imwe kana imwe yemishonga iyi. Varwere vakanga vasingagadziriswi kuti vagamuchire kana PCSK9 inhibitor pamwe chete nemishonga yemutemo, kana chirwere chemutemo chete. Cherechedza kuti hapana varwere vaibatwa chete nePCSK9 inhibitor.
Vose vatora zvidzidzo vakagamuchira zvinyorwa.
Izvo zvinoguma mune zvose izvi miedzo zvakanga zvakafanana-LDL cholesterol yakaderedzwa muvatachiwana vanowana PCSK9 inhibitor neanenge makumi matanhatu kubva muzana, zvichienzaniswa nemapoka ekurapa anobatwa neine statin oga. Iyi miedzo yepakutanga yakanga isinganyatsogadziriswa kuti ione kuvandudzwa kwemigumisiro yemwoyo, asi zviitiko zvakaonekwa muvanhu vakagadziriswa kugamuchira PCSK9 inhibitor vaivimbisa.
Mukupera kwegore ra2016, GLAGOV yakaratidza kuti, muna 968 vanhu vane coronary artery chirwere (CAD) avo vakanga vasina kurapwa pakurapa pamwe ne evolocumab pamwe chete nemufananidzo kana statin chete, avo vanogamuchira evolocumab vakawana (paavhareji) 1 muzana kuderedza muhuwandu ye- atherosclerotic plaques -yakagadzikana zvikuru.
Dambudziko rekutanga guru rakagadzirirwa kuongororwa zviitiko zvechipatara pane PCSK9 inhibitor, muedzo weFOURIER, yakabudiswa kutanga kwegore ra2017. Ichi chidzidzo chikuru chakanyoresa vanhu vanopfuura 27 000 vane CAD, uyezve vakaita kuti vawane evolocumab pamwe nemasimoni nemasitori oga. Mushure mokunge nguva yakawanda yekutevera yakapera mwedzi gumi nemaviri, zvigaro zvechipatara muboka re evolocumab zvakanyatsovandudzika kubva pane maonero ekutora, kunyange zvazvo zvishoma. Kunyanya, dambudziko rekurwadziwa kwemoyo rakaderedzwa ne 1.5 muzana, mukana wekuda kurapwa kwechirwere chisingaiti uyewo 1.5 muzana, uye ngozi yekurohwa ne 0.4 muzana. Chiitiko chekufa chakanga chisina kuderedzwa. Kunyange zvazvo zvichida kuti hukuru hwekliniki inobatsira ichavandudza nekuwedzerwa kwenguva yakawanda, kunyora kune zvimwe kuti ndiyo nyaya ichazotora mamwe makore mashoma.
Migumisiro Yakashata Na PCSK9 Inhibitors
Muchikoro chekuongorora nePCSK9 inhibitors, vazhinji vevarwere vaiva nemamwe madambudziko-zvikurukuru kugadziriswa kweganda panzvimbo yejojo, asi kupindira kwakashata kwakabatanidza kurwadziwa kwemasumbu (zvakafanana nemashure emigumisiro yemasimoni ) uye matambudziko emagetsi (kunyanya, amnesia uye kuora mwoyo kwepfungwa). Mune zvidzidzo zvekutanga izvi zvakasvibiswa nharaunda zvakaonekwa munenge 1 muzana yevarwere vakashandurwa kuPCSK9 inhibitor.
Nharaunda yezvinetso zvekuziva , apo yakaderera, yakamutsa dzimwe zviratidzo zvekuyeuchidza. Muchikamu chekudzidza kweFOURIER, hapana maonero akasiyana ekufungisisa kwebasa pakati pevanhu vanogamuchira evolocumab pamwe nemufananidzo, kana vachienzaniswa nevanhu vanogamuchira chimiro choga. Zvisinei, mubvunzo unoramba uripo kana kutyaira kwekutsvaga cholesterol kumazinga akaderera zvakanyanya kwenguva yakareba kungawedzera dambudziko rekushaya njere, chero zvipi zvinodhaka zvinoshandiswa kuita kudaro. Zvakare, nguva yakareba kwenguva inotevera inodiwa kuti uwane rubatsiro rwakanaka pamubvunzo uyu unokosha.
PCSK9 Inhibitors muPfungwa
IQCSK9 inhibitors inogona kuve yakakosha pakurapa cholesterol, uye mukuderedza mhepo yehutano. Zvisinei, pasinei nekushingaira kwose kunoratidzwa nevakawanda vemapurisa, tinofanirwa kuchengetedza zvinhu nenzira yakakodzera ikozvino.
Kutanga , apo mitsva yemwoyo nemishonga iyi mitsva inoratidzika kunge yakanyatsogadziriswa (mune zvidzidzo zvenguva pfupi), ukuru hwekuvandudza kusvika ikozvino haisi huru. Nguva yakareba yekutevera ichave yakakosha kuti uone kunyatsobatsirwa kwemishonga iyi-uye, kunyanya, kana ichange ichizopa nguva yakareba yekufa kwekubatsirwa.
Chechipiri , kufanana nezvose zvemazuva ano "zvinodhaka zvinodhaka" (zvinodhaka zvakagadzirirwa kune imwe majekiseni), iyo PCSK9 inhibitors yakanyanya, inodhura zvikuru. Kushandiswa kwavo, kunyanya mumakore ekutanga, kuchasvika kune vanhu vari pangozi yakanyanya, uye avo vane ngozi haigone kuderedzwa nemasimita-sevanhu vane mhuri ye hypercholesterolemia .
Chechitatu , apo madhiragi aya ari kutaurirwa nezvawo sechinotsiva shanduko yemitemo, tinofanirwa kunyatsocherechedza kuti makiriniki anoedza kusvika iye zvino avashandisa mukuwedzera kune mitemo, uye kwete panzvimbo yemashizha. Saka, isu hatina dhigirii dheti kuti titiudze kana vangave vangave vanogona kushandiswa nesimudzo.
Chechina , nepo hutano hwekuchengetedza hwePSK9 zvinodhaka kusvikira zvino hunovimbisa, huripo mibvunzo yakazaruka; kunyanya, kuti kana kutyaira cholesterol kune yakadzika mazinga kwenguva yakareba kungangove isina kukonzera zvishoma, kunyanya maererano nekugogodza.
> Sources:
> Nicholls SJ, Puri R, Anderson T, et al. Migumisiro yeEvolocumab Mukufambira Kwezvirwere zveCononary muvarwere veStatin-Treatment. The GLAGOV Randomized Clinical Trial. JAMA 2016. DOI: 10.1001 / jama.2016.16951
> Robinson JG, Farnier M, Krempf M, et al. Efficacy uye Kuchengetedzwa kweAricumcumab muRuchibing Lipids uye Mwoyo Yezviitiko. N Engl J Med 2015; DOI: 10.1056 / NEJMoa501031.
> Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab uye Clinical Outcomes muVachipatara vane Mwoyo Yehutano. N Engl J Med 2017; DOI: 10.1056 / NEJMoa1615664.
> Sabatine MS, Guigliano RP, Wiviott SD, et al. Efficacy uye Eafety yeEvolocumab muRucucing Lipids uye Mwoyo Yezviitiko. N Engl J Med 2015; DOI: 10.1056 / NEJMoa1500858.
> Stone NJ, Lloyd-Jones DM. Kunyoresa LDL Cholesterol Yakanaka, asi How and in Whom? N Engl J Med 2015; DOI: 10.1056 / NEJM1502192.