Klinička istraživanja zatajivanja srca s očuvanom ejekcijskom funkcijom

master's thesis

• Title (english): Clinical trials of heart failure with preserved ejection function
• Author: Dorja Sabljak
• Mentor: Maja Čikeš (mentor)
• Committee member: Tina Dušek (predsjednik povjerenstva)
• Committee member: Boško Skorić (član povjerenstva)
• Committee member: Maja Čikeš (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Zatajivanje srca je sindrom složene etiopatogeneze i jedan od najčešćih uzroka mortaliteta i morbiditeta u svijetu u osoba starijih od 65 godina. Unazad trideset godina predmet je proučavanja mnogih epidemioloških istraživanja, kliničkih randomiziranih studija i registara zatajivanja srca koji su dokazali različitost odgovora na farmakoterapiju ovisno o istisnoj frakciji lijeve klijetke i naglasili potrebu za izdvajanjem različitih podskupina zatajivanja srca na toj osnovi. Izdvojene su tri velike podskupine: zatajivanje srca s reduciranom istisnom frakcijom (HFrEF), zatajivanje srca s istisnom frakcijom srednjeg raspona (HFmrEF) i zatajivanje srca s normalnom to jest očuvanom istisnom frakcijom (HFpEF).
Definicija očuvane ili normalne istisne frakcije mijenjala se kroz godine i za sada ostala neistražen izazov za znanstvenike i kliničare. Bolesnici s HFpEF ne ostvaruju bolje ishode na terapiji ACE inhibitorima, ARB-ovima, beta-blokatorima i diureticima koji već dokazano smanjuju mortalitet i morbiditet u HFrEF bolesnika. HFpEF proporcija iznosi više od pedeset posto oboljelih od zatajivanja srca, a terapija je uglavnom empirijska prema komorbiditetima.
Obzirom na neuspjeh istraživanja terapija koje su učinkovite u HFrEF bolesnika, zaključeno je da su patofiziološki mehanizmi nastanka HFpEF-a različiti. Klinička istraživanja su se potom usmjerila na lijekove koji utječu na povećanje cGMP, ali bez uspjeha. Istraživanja sakubitril valsartana – neprilizinskog inhibitora u kombinaciji s ARB-om jedina su pokazala djelotvornost u fazi II istraživanja, a razmatraju se i brojne druge mogućnosti za liječenje oboljelih od HFpEF.

Abstract (english)

Heart failure is a syndrome of a complex etiopathogenesis and one of the most common causes of mortality and morbidity in the world in people over the age of 65. In the past thirty years, it has been studied through many epidemiological studies, clinical randomized trials and heart failure registries that have proven the difference in response to pharmacotherapy depending on the left ventricular ejection fraction (LVEF) and stressed the need to isolate various subgroups of heart failure on that basis. Three major subgroups were included: heart failure with reduced ejection fraction (HFrEF), heart failure with a normal/preserved fraction (HFpEF) and heart failure with mid-range ejection fraction (HFmrEF).
The definition of preserved or normal ejection fraction has changed over the years and for now, remains a challenge for scientists and clinicians. Patients with HFpEF do not achieve better outcomes on ACE inhibitors, ARBs, beta-blockers, and diuretics that have already been shown to reduce mortality and morbidity in HFrEF patients. HFpEF burdens more than fifty percent of heart failure patients, and therapy is mainly empirical according to comorbidities.
Given the failure to investigate therapies that are effective in HFrEF patients, it was concluded that the pathophysiological mechanisms of HFpEF are different. Clinical studies were then directed to drugs that affect cGMP increase, but without success. Investigations of sacubitril/valsartan - neprilysin inhibitor in combination with ARB were the only ones that
demonstrated efficacy in phase II research, and many other possibilities are being considered for the treatment of HfpEF patients.

• Keywords: zatajivanje srca; HFpEF; kliničko istraživanje
• Keywords (english): heart failure; HFpEF; clinical trial
• Language: croatian
• URN:NBN: urn:nbn:hr:105:981937
• 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: 2024-09-26 12:24:27