{"id":2741,"date":"2023-02-09T20:41:22","date_gmt":"2023-02-09T20:41:22","guid":{"rendered":"https:\/\/www.karotidnahirurgija.com\/?page_id=2741"},"modified":"2023-02-24T12:29:49","modified_gmt":"2023-02-24T12:29:49","slug":"7-12-terapija-statinima","status":"publish","type":"page","link":"https:\/\/www.karotidnahirurgija.com\/?page_id=2741","title":{"rendered":"7.2. TERAPIJA STATINIMA"},"content":{"rendered":"

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MEDIKAMENTOZNA TERAPIJA KAROTIDNE BOLESTI<\/h1>\n

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7.2. TERAPIJA STATINIMA<\/p>\n

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TERAPIJA STATINIMA<\/h5>\n

Statini<\/b> <\/b>sni\u017eavaju nivo serumskog holesterola, inhibicijom aktivnosti enzima HMG CoA reduktaze koji je klju\u010dni enzim u ranim fazama sinteze holesterola u jetri.<\/p>\n

Rezultati prospektivnih studija govore o koristi terapije statinima u osoba sa dislipidemijom. Ultrazvu\u010dni i angiografski nalazi potvr\u0111uju uticaj statina na uspo- ravanje progresije ateroskleroze. Morbiditet i mortalitet vezan za infarkt srca i mozga je ni\u017ei pri terapiji statinima. Primena statina u osoba sa karotidnom bole\u0161\u0107u zaustavlja progresiju ili \u010dak indukuje regresiju ateroskleroze.<\/p>\n

U SPARCL studiji 4732 bolesnika sa skora\u0161njim mo\u017edanim udarom ili TIA je randomizovano u dve grupe.15<\/span><\/sup> <\/span><\/sup>Prva grupa pacijenata je dobijala 80mg atorvastatina dnevno, dok je druga, kontrolna grupa bila placebo. Redukcija relativnog rizika od razvoja mo\u017edanog udara iznosila je 16% u korist atorvastatin grupe. Analizom podgrupe pacijenata (1007 pacijenata) sa dokazanom bole\u0161\u0107u karotidnih arterija koji su bili na statinskoj terapiji, zabele\u017eena je redukcija relativnog rizika od kasnog mo\u017edanog udara od 33% i 42% RRR od velikih koronarnih komplikacija.8<\/span><\/sup> <\/span><\/sup>Za razliku od prethodno pomenute Express<\/i> <\/i>studije, u kojoj je medikamentna terapija ordinirana u prvih 24 \u010dasa od mo\u017edanog udara ili TIA-a, u SPARCL studiju su uklju\u010deni pacijenti koji su pretrpeli mo\u017edani udar ili TIA u periodu od jedan do \u0161est meseci od po\u010detka terapije. Prose\u010dna du\u017eina perioda od ishemijskog doga\u0111aja do randomizacije iznosila je 90 dana. Uzimaju\u0107i u obzir \u010dinjenicu da pribli\u017ena u\u010destalost ponovnog mo\u017edanog udara u pacijenata sa ipsilateralnom karotidnom stenozom, tokom prvih 30 dana, iznosi 10%, verovatno je da su mnogi od ovih pacijenata imali \u0161log pre nego \u0161to su i uklju\u010deni u ispitivanje. S toga se opravdano postavlja pitanje koliko bi ve\u0107i bio klini\u010dki benefit u ovih pacijenata da je medikamentna terapija zapo\u010deta ranije.15<\/span><\/sup> <\/span><\/sup>Rezultati MIRACL studije govore u prilog ranog zapo\u010dinjanja statinske terapije. Pacijenti sa akutnim koronarnim sindromom su podeljeni u dve grupe, kontrolnu, placebo i grupu pacijenata kojima je ordiniran atorvastatin tokom prva dva dana. Pacijenti su pra\u0107eni \u0161esnaest nedelja i zaklju\u010deno je da je agresivna rana terapija atorvastatinom povezana sa 16% RRR od razvoja sekundarnih koronarnih doga\u0111aja.<\/p>\n<\/div>\n

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Prikaz strukture lipoproteina sa trgliceridima i holesterolskim estrima u jezgru i slobodnim holesterolom uz apolipoprotein na povr\u0161ini.<\/em><\/p>\n<\/div>\n

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Autori HPS studije (Heart Protection Study) ispitivali su uticaj statinske terapije, u pore\u0111enju sa placebom, na u\u010destalost ne\u017eeljenih kardiovaskularnih doga\u0111aja u pacijenata koji su ranije imali cerebrovaskularne simptome. <\/span><\/sup>U statinskoj grupi je postignuta 23,6% RRR od smrtnog ishoda, infarkta miokarda, mo\u017edanog udara i potrebe za hirur\u0161kom revaskularizacijom. Me\u0111utim, u\u010destalost kasnog mo\u017edanog udara, posmatrano posebno, nije zna\u010dajnije smanjena statinskom terapijom, te je verovatno da se ve\u0107i benefit posti\u017ee na polju kardiolo\u0161ke prevencije. Mogu\u0107e obja\u0161njenje je \u010dinjenica da su pacijenti randomizovani u proseku 4,3 godine nakon manifestacije cerebrovaskularnih simptoma.<\/p>\n

Prema tome, kod pacijenata sa simptomatskom karotidnom stenozom, statinsku terapiju treba zapo\u010deti \u0161to je ranije mogu\u0107e. Pitanja koje se ovde postavljaju su da li postoji vrednost holesterola ispod koje statini vi\u0161e nemaju efekta i da li nekim pacijentima statinska terapija uop\u0161te nije ni potrebna. Brojni su dokazi da \u0161to je ni\u017ea vrednost holesterola, manja je i u\u010destalost aterosklerotskih komplikacija, bez porasta u\u010destalosti prate\u0107ih ne\u017eeljenih efekata statina.15,18,19,20<\/span><\/sup> <\/span><\/sup>U SPARCL studiji, prose\u010dna vrednost LDL holesterola iznosila je 73mg\/ dl, odnosno 1,8mmol\/l tokom 5 godina terapije atorvastatinom, bez razlike u u\u010destalosti ne\u017eeljenih efekata u odnosu na placebo. U studiji 10 hiljada pacijenata sa stabilnom ishemijskom bole\u0161\u0107u srca, na\u0111eno je da je najve\u0107i klini\u010dki benefit od statinske terapije postignut u grupi pacijenta sa najni\u017eim vrednostima LDL holesterola (u proseku od 53 mg\/dl, odnosno 1,3 mmol\/l) i to bez porasta broja ne\u017eeljenih efekata.18<\/span><\/sup><\/p>\n

Nije utvr\u0111eno da postoji vrednost LDL holesterola, ispod koje je blokirano pozitivno dejstvo statina, pa je agresivna statinska terapije korisna kod skoro svih pacijenata sa stenozom karotidnih arterija.<\/p>\n

Za statinsku terapiju kod asimptomatskih pacijenata jo\u0161 uvek nema dovoljno podataka obezbe\u0111enih velikim randomizovanim ispitivanjima. Me\u0111utim,<\/p>\n

prema<\/span> <\/span>preporukama<\/span> <\/span>ESI,<\/span> <\/span>statini <\/span> <\/span>treba<\/span> <\/span>da<\/span> <\/span>budu<\/span> <\/span>standardna<\/span> <\/span>terapija<\/span> <\/span>kod<\/span> <\/span>svih<\/span> <\/span>asimptomatskih<\/span> <\/span>pacijenata,<\/span> <\/span>ukoliko<\/span> <\/span>njihova<\/span> <\/span>upotreba<\/span> <\/span>nije<\/span> <\/span>kontraindikovana.<\/span>14<\/span><\/sup><\/p>\n

Holesterol<\/b><\/span> <\/b><\/span>nezavisni,<\/b><\/span> <\/b><\/span>pleiotropni<\/b><\/span> <\/b><\/span>efekti<\/b><\/span> <\/b><\/span>statina<\/span> <\/span>su;<\/span><\/p>\n

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  • pove\u0107anje<\/span> <\/span>ekspresije<\/span> <\/span>sintetaze<\/span> <\/span>azot monoksida<\/span> <\/span>i<\/span> <\/span>pove\u0107ana produkciji<\/span> <\/span>NO<\/span> <\/span>i<\/span> <\/span>popravljanje<\/span> <\/span>endotelne<\/span> <\/span>disfunkcije<\/span><\/li>\n
  • smanjenje<\/span> <\/span>adhezije<\/span> <\/span>leukocita<\/span> <\/span>i<\/span> <\/span>makrofaga<\/span> <\/span>za<\/span> <\/span>endotel<\/span> <\/span>i<\/span> <\/span>imunomodulacija<\/span><\/li>\n
  • smanjenje<\/span> <\/span>apoptoze<\/span> <\/span>endotelnih<\/span> <\/span>\u0107elija,<\/span><\/li>\n
  • pove\u0107anje<\/span> <\/span>apoptoze<\/span> <\/span>mi\u0161i\u0107nih<\/span> <\/span>\u0107elija,<\/span><\/li>\n
  • smanjenje<\/span> <\/span>proliferacije<\/span> <\/span>glatkih<\/span> <\/span>mi\u0161i\u0107nih<\/span> <\/span>\u010delija<\/span> <\/span>unutar<\/span> <\/span>plaka,<\/span><\/li>\n
  • smanjenje<\/span> <\/span>aktivnosti<\/span> <\/span>lokalnih<\/span> <\/span>makrofaga<\/span> <\/span>i<\/span> <\/span>produkcije<\/span> <\/span>metaloproteinaza,<\/span><\/li>\n
  • inhibicija nakupljanja <\/span> <\/span>trombocita na <\/span> <\/span>povr\u0161ini <\/span> <\/span>endotela, <\/span> <\/span>favorizovanje<\/span> <\/span>fibrinolize<\/span> <\/span>i<\/span><\/li>\n
  • sni\u017eavanje<\/span> <\/span>vrednosti<\/span> <\/span>hs<\/span> <\/span>CRPa<\/span> <\/span>(<\/span>high<\/i><\/span> <\/i><\/span>specific<\/i><\/span> <\/i><\/span>CRP<\/i><\/span>)<\/span> <\/span>najsenzitivnijeg<\/span> <\/span>markera<\/span> <\/span>aktivnosti<\/span> <\/span>inflamacije<\/span> <\/span>u<\/span> <\/span>sklopu<\/span> <\/span>aterosklerotskog<\/span> <\/span>procesa.<\/span><\/li>\n<\/ul>\n

    Pleiotropni<\/span> <\/span>efekti<\/span> <\/span>statina<\/span> <\/span>doprinose<\/span> <\/span>spre\u010davanju<\/span> <\/span>razvoja<\/span> <\/span>ateroskleroze,<\/span> <\/span>ali<\/span> <\/span>i<\/span> <\/span>prevencija<\/span> <\/span>neointimalne<\/span> <\/span>hiperplazije<\/span> <\/span>nakon<\/span> <\/span>revaskularizacije<\/span> <\/span>vakularnim<\/span> <\/span>ili<\/span> <\/span>endovasklularnim<\/span> <\/span>intervencijama.<\/span><\/p>\n

    Statini<\/b><\/span> <\/b><\/span>i<\/b><\/span> <\/b><\/span>rezultati<\/b><\/span> <\/b><\/span>klini\u010dkih<\/b><\/span> <\/b><\/span>studija<\/b><\/span><\/p>\n

    V<\/span>eliki<\/span> <\/span>broj<\/span> <\/span>klini\u010dkih<\/span> <\/span>studija<\/span> <\/span>je<\/span> <\/span>pratio<\/span> <\/span>efekat<\/span> <\/span>pojedinih<\/span> <\/span>statina<\/span> <\/span>kao<\/span> <\/span>monoterapije<\/span> <\/span>na<\/span> <\/span>progresiju\/regresiju<\/span> <\/span>ateroskleroze<\/span> <\/span>kod<\/span> <\/span>bolesnika<\/span> <\/span>sa<\/span> <\/span>verifikovanom<\/span> <\/span>koronarnom<\/span> <\/span>i<\/span> <\/span>perifernom<\/span> <\/span>ateroskleroti\u010dnom<\/span> <\/span>bolesti.<\/span> <\/span>Rezultati<\/span> <\/span>ovih<\/span> <\/span>studija<\/span> <\/span>statinima konzistentno<\/span> <\/span>su<\/span> <\/span>pokazali<\/span> <\/span>povoljan<\/span> <\/span>efekat<\/span> <\/span>ove<\/span> <\/span>terapije<\/span> <\/span>na<\/span> <\/span>usporavanje<\/span> <\/span>progresije<\/span> <\/span>bolesti,<\/span> <\/span>a<\/span> <\/span>u<\/span> <\/span>nekim<\/span> <\/span>slu\u010dajevima<\/span> <\/span>i<\/span> <\/span>mogu\u0107nost<\/span> <\/span>regresije<\/span> <\/span>aterosklerotskog<\/span> <\/span>plaka.<\/span><\/p>\n

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    • \n

      Utvrdjena<\/span> <\/span>je<\/span> <\/span>korelacija<\/span> <\/span>izme\u0111u<\/span> <\/span>efekta<\/span> <\/span>statina<\/span> <\/span>na<\/span> <\/span>proces<\/span> <\/span>ateroskleroze<\/span> <\/span>i<\/span> <\/span>stepen<\/span> <\/span>redukcije<\/span> <\/span>lipidnih<\/span> <\/span>frakcija.<\/span><\/p>\n<\/li>\n

    • \n

      Promene<\/span> <\/span>u<\/span> <\/span>srednjem<\/span> <\/span>i<\/span> <\/span>minimalnom<\/span> <\/span>dijametru<\/span> <\/span>stenoze<\/span> <\/span>uvek<\/span> <\/span>su<\/span> <\/span>bile<\/span> <\/span>udru\u017eene<\/span> <\/span>sa<\/span> <\/span>smanjenjem<\/span> <\/span>incidence<\/span> <\/span>kardiovaskularnih<\/span> <\/span>doga\u0111aja<\/span> <\/span>u<\/span> <\/span>bolesnika<\/span> <\/span>koji<\/span> <\/span>su<\/span> <\/span>podvrgnuti<\/span> <\/span>statisnkoj<\/span> <\/span>terapiji.<\/span><\/p>\n<\/li>\n

    • \n

      <\/span>Regresija<\/span> <\/span>aterogeneze<\/span> <\/span>uo\u010dena<\/span> <\/span>je<\/span> <\/span>i<\/span> <\/span>u<\/span> <\/span>bolesnika<\/span> <\/span>sa<\/span> <\/span>normalnim<\/span> <\/span>po\u010detnim vrednostima<\/span> <\/span>holeterola<\/span> <\/span>i<\/span> <\/span>LDL.<\/span><\/p>\n<\/li>\n<\/ul>\n

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      • \n

        Duplex<\/span> <\/span>ultrasonografija,<\/span> <\/span>sa<\/span> <\/span>B-mod<\/span> <\/span>ultrazvukom<\/span> <\/span>pokazala<\/span> <\/span>je<\/span> <\/span>superiornu<\/span> <\/span>senzitivnost<\/span> <\/span>i<\/span> <\/span>specifi\u010dnost<\/span> <\/span>ove<\/span> <\/span>vizuelizaione<\/span> <\/span>metode<\/span> <\/span>u<\/span> <\/span>kvantifikaciji<\/span> <\/span>evolucije<\/span> <\/span>aterosklerotskog<\/span> <\/span>plaka.<\/span><\/p>\n<\/li>\n<\/ul>\n

        Anjonske<\/b><\/span> <\/b><\/span>smole<\/b><\/span> <\/b><\/span>(holestiramin<\/span> <\/span>i<\/span> <\/span>holestipol)<\/span> <\/span>se<\/span> <\/span>vezuju<\/span> <\/span>za<\/span> <\/span>\u017eu\u010dne<\/span> <\/span>kiseline<\/span> <\/span>u<\/span> <\/span>crevima<\/span> <\/span>\u010dime<\/span> <\/span>se<\/span> <\/span>ubrzava<\/span> <\/span>katabolizam<\/span> <\/span>holesterola<\/span> <\/span>u<\/span> <\/span>jetri<\/span> <\/span>i<\/span> <\/span>sni\u017eava<\/span> <\/span>njegov<\/span> <\/span>nivo<\/span> <\/span>u<\/span> <\/span>krvi.<\/span> <\/span>Anjonske<\/span> <\/span>smole<\/span> <\/span>se<\/span> <\/span>ne<\/span> <\/span>resorbuju<\/span> <\/span>tako<\/span> <\/span>da<\/span> <\/span>ne<\/span> <\/span>ispoljavaju<\/span> <\/span>sistemske<\/span> <\/span>efekte.<\/span> <\/span>Najvi\u0161e<\/span> <\/span>sni\u017eavaju<\/span> <\/span>nivo<\/span> <\/span>LDL<\/span> <\/span>holesterola,<\/span> <\/span>ne<\/span> <\/span>smanjuju<\/span> <\/span>bitno<\/span> <\/span>vrednosti<\/span> <\/span>triglicerida,<\/span> <\/span>a<\/span> <\/span>pove\u0107anja<\/span> <\/span>vrednosti<\/span> <\/span>HDL<\/span> <\/span>holesterola<\/span> <\/span>su<\/span> <\/span>manja<\/span> <\/span>od<\/span> <\/span>10%.<\/span> <\/span>Pojavom<\/span> <\/span>statina<\/span> <\/span>izgubili<\/span> <\/span>su<\/span> <\/span>nekada\u0161nji<\/span> <\/span>zna\u010daj.<\/span><\/p>\n

        Fibrati<\/b> <\/b>pove\u0107avaju aktivnost lipoprotein lipaze, smanjuju sintezu VLDL lipoproteina i pove\u0107avaju klirens triglicerida iz plazme. Od svih hipolipidemika, fibrati najvi\u0161e sni\u017eavaju nivoe triglicerida i VLDL holesterola (40-60%), a pove\u0107avaju vrednost HDL holesterola (15-25%). U klini\u010dkoj primeni su gemfibrozil, fenofibrat i ciprofibrat. Pojavom statina, koriste se kao dodatna terapija.<\/p>\n

        Istra\u017eivanja koja su u toku \u0107e pokazati da li Ezetimibe<\/b><\/i>, novi preparat koji inhibira apsorpciju holesterola sa crevne sluznice, uti\u010de na smanjenje rizika od mo\u017edanog udara. S druge strane, razvoj lekova koji uti\u010du na porast nivoa HDL holesterola je u toku.<\/p>\n

        Antioksidansi<\/b> <\/b>(tokoferol, flavonoidi, beta karoten, vitamin C i dr.) mogu da uspore progresiju arterioskleroze. Antiaterogeno dejstvo alfa-tokoferola, u inicijalnoj fazi aterogenezie sni\u017eava adhezivnost endotela, aktivnost trombocita, osloba\u0111anje superoksidnih anjona u monocitima, lipidnu oksidaciju i nivo interleukina (IL-1 beta), koji je ina\u010de proinflamatorne prirode.<\/p>\n<\/div>\n


        \n<\/p>\n","protected":false},"excerpt":{"rendered":"

        MEDIKAMENTOZNA TERAPIJA KAROTIDNE BOLESTI 7.2. TERAPIJA STATINIMA TERAPIJA STATINIMA Statini sni\u017eavaju nivo serumskog holesterola, inhibicijom aktivnosti enzima HMG CoA reduktaze koji je klju\u010dni enzim u ranim fazama sinteze holesterola u jetri. Rezultati prospektivnih studija govore o koristi terapije statinima u osoba sa dislipidemijom. Ultrazvu\u010dni i angiografski nalazi potvr\u0111uju uticaj statina na uspo- ravanje progresije ateroskleroze. […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-2741","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"\n7.2. 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