Liječenje hiperlipidemija PCSK9 inhibitorima

master's thesis

• Title (english): Treatment of hyperlipidemia with PCSK9 inhibitors
• Author: Mihovil Santini
• Mentor: Martina Lovrić Benčić (mentor)
• Committee member: Mislav Puljević (predsjednik povjerenstva)
• Committee member: Boško Skorić (član povjerenstva)
• Committee member: Martina Lovrić Benčić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2022-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Kardiovaskularne i cerebrovaskularne bolesti vodeći su uzrok smrti u Hrvatskoj i svijetu. Jedan od najvažnijih faktora rizika za razvoj kardiovaskularnih bolesti je hiperlipidemija. Iz tog razloga liječenje hiperlipidemija i održavanje ciljnih vrijednosti kolesterola ističu se kao jedan od najvažnijih ciljeva u prevenciji i liječenju kardiovaskularnih bolesti. Unatoč širokoj i dugogodišnjoj primjeni statina, ezetimiba i ostalih antilipemika, neki pacijenti ipak ne postižu ciljne vrijednosti kolesterola, dok se kod drugih očituju ne tako rijetke nuspojave navedenih lijekova, posebice statina. Samim time nije moguć nastavak terapije i optimalno liječenje bolesnika. Dugi niz godina tragalo se za novim načinom liječenja povišenih vrijednosti lipida te su se PCSK9 inhibitori nametnuli kao novi i efikasan terapijski pristup. Otkriće PCSK9 molekule 2003. godine te razvoj efikasnih monoklonalnih antitijela prethodili su odobrenju dva trenutačno dostupna monoklonalna antitijela, alirokumaba i evolokumaba. Vezanjem za serinsku proteazu PCSK9, monoklonalna antitijela sprječavaju interakciju PCSK9 s LDL-receptorima i posljedično tome ne dolazi do degradacije LDL-receptora. Navedeni mehanizam dovodi do znatne redukcije razine LDL-C. Alirokumab i evolokumab primjenjuju se u obliku supkutanih injekcija jednom svaka dva tjedna ili jednom mjesečno. Mjesta najčešće primjene su trbuh, bedro i nadlaktica. Osim što dovode do sniženja razine LDL-C, dovode i do značajnog smanjenja rizika od neželjenih kardiovaskularnih događaja. Ovi lijekovi pokazuju dobru podnošljivost, a od nuspojava je najčešća reakcija na mjestu primjene injekcije. PCSK9 inhibitori danas su sastavni dijelovi smjernica za liječenje hiperlipidemija.

Abstract (english)

Cardiovascular and cerebrovascular diseases are the leading cause of death in Croatia and the world. One of the most important risk factors for the development of cardiovascular diseases is hyperlipidemia. For this reason, the treatment of hyperlipidemia and the maintenance of cholesterol target levels stand out as one of the most important goals in the prevention and treatment of cardiovascular disease. Despite the wide and long-term use of statins, ezetimibe and other lipid-lowering agents, some patients still do not reach the target cholesterol levels, while others have not so rare side effects of these drugs, especially statins. Therefore those patients cannot continue therapy and optimal treatment. For many years, a new way of treating elevated lipid levels has been sought, and PCSK9 inhibitors have emerged as a new and effective therapeutic approach. The discovery of the PCSK9 molecule in 2003 and the development of effective monoclonal antibodies preceded the approval of two currently available monoclonal antibodies, alirocumab and evolocumab . By binding to the serine protease-PCSK9, monoclonal antibodies prevent PCSK9 from interacting with LDL receptors and consequently no LDL receptor degradation occurs. This mechanism leads to a significant reduction in LDL-C levels. Alirocumab and evolocumab are given as subcutaneous injections once every two weeks or once a month. The most common sites of application are the abdomen, thigh and upper arm. In addition to lowering LDL-C levels, they also lead to a significant reduction in the risk of adverse cardiovascular events. These drugs show good tolerability and the most common side effect is an injection site reaction. PCSK9 inhibitors are now an integral part of guidelines for the treatment of hyperlipidemia.

• Keywords: hiperlipidemija; monoklonalna antitijela; PCSK9
• Keywords (english): hyperlipidemia; monoclonal antibodies; PCSK9
• Language: croatian
• URN:NBN: urn:nbn:hr:105:958157
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-02-15 11:51:40