Antikoagulantna terapija u bolesnika s fibrilacijom atrija i kroničnom renalnom insuficijencijom

master's thesis

• Title (english): Anticoagulant therapy in patients with atrial fibrillation and chronic renal insufficiency
• Author: Marta Popović
• Mentor: Matias Trbušić (mentor)
• Committee member: Vjekoslav Radeljić (predsjednik povjerenstva)
• Committee member: Boško Skorić (član povjerenstva)
• Committee member: Matias Trbušić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2020-07-17, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Fibrilacija atrija je najčešća poznata srčana aritmija povezana s izrazito povišenim rizikom od moždanog udara i sistemskih tromboembolija. Kako bi se taj rizik smanjio nužno je većini bolesnika s fibrilacijom atrija uvesti doživotnu oralnu antikoagulantnu terapiju. Velik udio ovih bolesnika uz fibrilaciju atrija boluje i od kronične renalne insuficijencije, koja sama po sebi može također biti povezana s povišenim rizikom od tromboembolijskih događaja, ali i s povišenim rizikom od krvarenja. Stoga je važno bolesnicima s fibrilacijom atrija i renalnom insuficijencijom pažljivo odabrati vrstu i dozu antikoagulantne terapije koja će za njih biti najučinkovitija, ali i najsigurnija. Trenutno postoje dvije skupine oralnih antikoagulansa, prvu čine antagonisti vitamina K s
glavnim predstavnikom varfarinom, a drugu novi oralni antikoagulansi (NOAK) čiji su predstavnici dabigatran, rivaroksaban, apiksaban i edoksaban. Budući da se NOAK-i visokim udjelom izlučuju renalnim putem, velika klinička istraživanja NOAK-a uključila su samo bolesnike s blagom i umjerenom renalnom insuficijencijom te je dokazano da su za ovu skupinu bubrežnih
bolesnika s fibrilacijom atrija NOAK-i lijek izbora. Farmakokinetičkim istraživanjima ispitani su učinkovitost i sigurnost antikoagulantnih lijekova u bolesnika s teškom renalnom insuficijencijom i onih s bubrežnim zatajenjem kojima su nađene doze
NOAK-a koje bi mogle biti učinkovite i ostvarivati stabilne plazmatske razine čak i u ovih bolesnika. Podaci o učinkovitosti varfarina u bolesnika s teškom renalnom insuficijencijom prilično su heterogeni pa nije moguće sa sigurnošću zaključiti smanjuje li varfarin rizik tromboembolije u ovih bolesnika ili ga čak i povećava. Prema dostupnim istraživanjima teška krvarenja su također manje učestala u bolesnika s teškom renalnom insuficijencijom koji koriste NOAK-e nego u korisnika varfarina. Osim krvarenja, važan faktor sigurnosti u ovih bolesnika je i rizik od progresije bubrežne bolesti i pojave akutne bubrežne ozljede. Poseban oblik
bubrežne ozljede pod nazivom nefropatija povezana s upotrebom antikoagulansa javlja se češće u korisnika varfarina i može uzrokovati ubrzanu progresiju bolesti i dovesti bolesnike s blagom renalnom insuficijencijom do potrebe za hemodijalizom. Uzevši u obzir superiorni sigurnosni profil i mogućnost postizanja stabilnih plazmatskih razina i u teškoj renalnoj insuficijenciji NOAK-i se čine kao bolja opcija antikoagulantne terapije u bolesnika s fibrilacijom atrija i kroničnom renalnom insuficijencijom.

Abstract (english)

Atrial fibrillation is the most common cardiac arrhythmia and it is associated with a significantly increased risk of stroke and systemic embolism. To reduce this risk it is important to start these patients on life-term oral anticoagulation. Many patients with atrial fibrillation also have some degree of renal insufficiency, which further increases the risk of stroke and
thromboembolism, as well as the risk of bleeding. Therefore it is crucial to carefully choose a type of anticoagulant medication that is effective and safe for patients suffering from atrial fibrillation and renal insufficiency. There are two types of oral anticoagulants, vitamin K antagonists and new oral anticoagulants (NOAC). Warfarin is the most commonly used vitamin K antagonist, while NOACs include dabigatran, rivaroxaban, apixaban and edoxaban. Considering NOACs are mostly renally excreted, only patients with mild to moderate renal insufficiency were included in the original clinical trials, but these trials showed that NOACs are as effective or superior to warfarin and are now the treatment of choice for patients with atrial fibrillation and mild or moderate renal insufficiency. Few NOAC pharmacokinetic studies were performed and found doses of these drugs that produce stable plasma levels in patients with severe renal insufficiency and could be effective in preventing thromboembolism. The results of studies that included warfarin treatment in these patients are heterogeneous, showing it could produce a satisfactory anticoagulant effect or it could even increase the stroke risk. Major bleeding also seems to be less frequent in patients with severe renal insufficiency treated with NOACs then in those treated with warfarin. Besides bleeding, an important factor of safety to keep in mind while treating patients with renal insufficiency is the progression of their kidney disease and the development of acute kidney injury. A specific type of kidney injury known as
anticoagulant related nephropathy is a severe adverse effect of oral anticoagulant therapy, related mostly to warfarin use. It can occur even in patients with mild renal insufficiency or normal kidney function, often leading to life-long hemodialysis. Considering their superior safety profile as well as the possibility of achieving stable plasma levels even in severe kidney
disease, NOACs seem to be a better option for anticoagulant treatment of patients with atrial fibrillation and renal insufficiency.

• Keywords: atrijska fibrilacija; kronična renalna insuficijencija; antikoagulantna terapija
• Keywords (english): atrial fibrillation; chronic renal insufficiency; anticoagulant treatment
• Language: croatian
• URN:NBN: urn:nbn:hr:105:331199
• 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: 2021-03-30 09:01:27