| Abstract | Fibrilacija atrija (FA) je nakon ekstrasistolije najčešća značajna aritmija. Karakterizira je gubitak atrijske kontrakcije što pogoduje stvaranju tromba, osobito u lijevoj aurikuli, koja samim time postaje tipično izvorište tromboembolije, najčešće cerebralne. Zbog toga je ishemijski moždani udar (IMU) najčešći kardiovaskularni štetni događaj koji se pojavljuje kod bolesnika s FA. Bolesnici s FA skloniji su stvaranju muralnih krvnih ugrušaka u lijevom atriju (LA) i to najčešće u lijevoj aurikuli (LAA od eng. left atrial appendage) što povećava rizik nastanka MU, ali i ostalih sistemnih tromboembolijskih incidenata. Liječenje bolesnika s FA ima dva osnovna cilja. Prvi je kontrola simptoma antiaritmicima, kardioverzijom ili kateterskom ablacijom, a drugi je smanjenje tromboemboliskih komplikacija antikoagulantnom terapijom. Sukladno svemu navedenom, jedina terapija koja jasno utječe na prognozu FA, odnosno smanjuje smrtnost i invaliditet, jest upravo antikoagulantna terapija. U prevenciji tromboembolijskih incidenata kod bolesnika s FA postoje dvije glavne skupine peroralnih antikoagulanasa. Prva skupina su antagonisti vitamina K (VKA), varfarin. Drugu skupinu čine nova generacija oralnih antikoagulanasa (NOAK) u koju spadaju direktni inhibitori trombina čiji je predstavnik dabigatran (Pradaxa®) i oralni inhibitori faktora Xa, a čiji su predstavnici rivaroksaban (Xarelto®) i apiksaban (Eliquis®). U posljednjih nekoliko godina odobravaju se novi lijekovi za liječenje ili profilaksu tromboembolijskih događaja u stanjima kao što su FA, akutni koronarni sindrom, plućna embolija (PE), duboka venska tromboza (DVT), arterijska periferna bolest i dr. Razlog tomu je što jedan od najčešće primjenjivanih lijekova, varfarin, iako klinički dokazane učinkovitosti i u liječenju i u prevenciji, ima niz nedostataka: puno nuspojava, brojne interakcije s hranom, alkoholom i drugim lijekovima zbog čega zahtjeva pažljivo i učestalo laboratorijsko praćenje antikoagulacijskog učinka pomoću INR-a te stoga dovodi do nesuradljivosti bolesnika s jedne te do nedovoljnog propisivanja od liječnika s druge strane. Nakon objave rezultata niza velikih kliničkih istraživanja kao što su studije RE-LY, ROCKET AF, AVERROES i ARISTOTLE, odobrenja regulatornih tijela u Europskoj uniji, EMA (eng. European Medicines Agency) i Sjedinjenim Američkim Državama, FDA (eng. Food and Drug Administration) te stvarnog uvođenja NOAK-a u kliničku praksu bili su i više nego dovoljni razlozi za izdavanje najnovijih nadopuna Smjernicama Europskog kardiološkog društva za liječenje bolesnika s FA u kolovozu 2012. godine. U toj se nadopuni suštinski mijenja preporuka za antikoagulantnu terapiju kod bolesnika s nevalvularnom FA, (NVAF od eng. Nonvalvular Atrial Fibrillation). Naime, prvi put se NOAK u potpunosti i bez zadrške izjednačava s varfarinom. Iz ovih nekoliko velikih kliničkih studija možemo zaključiti kako NOAK-i smanjuju rizik tromboembolijskih incidenata kod bolesnika s NVAF-om u jednakoj ili većoj mjeri u odnosu na varfarin, što je vrlo bitna klinička prednost NOAK-a. Također, može se zaključiti jednaka ili manja učestalost velikih krvarenja, posebno intrakranijskih, u odnosu na varfarin, što je još jedna bitna prednost NOAK-a u odnosu na varfarin. Velika prednost NOAK-a je njihova predvidljiva farmakokinetika i farmakodinamika zbog čega ne zahtijevaju rutinsko praćenje koagulacije kao što je slučaj s varfarinom. Također, NOAK-i imaju kratak poluvijek u plazmi, što je bitna prednost u slučaju predoziranja i krvarenja. Nedostatak NOAK-a je taj što je samo antidot za dabigatran registriran i dostupan na tržištu lijekova, dok su za rivaroksaban i apiksaban u fazama istraživanja. Nova generacija oralnih antikoagulanasa (dabigatran, rivaroksaban i apiksaban) predstavlja znatan napredak u prevenciji tromboemboliskih incidenata (MU i SE) u bolesnika s FA s obzirom na dotad jedini lijek, varfarin. NOAK-i su pokazali više prednosti nego nedostataka u odnosu na varfarin i time bitno povećali sigurnost prevencije MU u bolesnika s FA. |
| Abstract (english) | Atrial fibrillation (AF) is the most frequent arrhythmia immediately after extrasystoles. It is characterized by loss of atrial contraction, which favors the creation of a thrombus, especially in the left atrial appendage (LAA), which is becoming a typical source of thromboembolism, most commonly cerebral. Therefore, ischemic stroke is the most common cardiovascular event occurring in patients with AF. Patients with AF are more likely to develop mural blood clots in the left atrium (LA), most commonly in the LAA, which increases the risk of ischemic stroke, but also other systemic thromboembolic incidents. Treatment of patients with AF has two basic goals. The first is the control of symptoms with antiarrhythmic, cardioversion or catheter ablation, and the second is the reduction of thromboembolic complications by anticoagulant therapy. In accordance with all the above, the only therapy that clearly affects the prognosis of AF, reduces mortality and disability, is just anticoagulant therapy. In the prevention of thromboembolic incidents in patients with AF there are two main groups of oral anticoagulants. The first group are vitamin K antagonists (VKA), warfarin. The second group consists of a new generation of oral anticoagulants (NOACs) including direct thrombin inhibitors whose representative is dabigatran (Pradaxa®) and oral factor Xa inhibitors, with rivaroxaban (Xarelto®) and apixaban (Eliquis®) agents. In recent years, new drugs are approved for the treatment or prophylaxis of thromboembolic events in conditions such as FA, acute coronary syndrome, pulmonary embolism, deep vein thrombosis, arterial peripheral disease and others. This is why one of the most commonly used drugs, warfarin, although clinically proven to be effective in both treatment and prevention, has a number of drawbacks: many side effects, numerous interactions with food, alcohol and other drugs, therefore requiring careful and frequent laboratory monitoring of anticoagulant effect by INR and hence leading to patient unreliability, on the one hand, and to the insufficient prescription of the doctor, on the other hand. Following the announcement of the results of a series of major clinical investigations such as RE-LY, ROCKET AF, AVERROES and ARISTOTLE studies, regulatory approvals from the European Union, EMA (European Medicines Agency) and the United States, FDA (Food and Drug Administration) and the actual introduction of NOAC into clinical practice were more than enough reasons to issue the most recent supplement to the European Cardiac Society Guidelines for the treatment of patients with AF in August 2012. This supplement essentially alters the recommendation for anticoagulant therapy in patients with nonvalvular AF (NVAF). Namely, for the first time, NOAC fully and equally equates to warfarin. From these several major clinical studies we can conclude that NOAC reduce the risk of thromboembolic incidence in patients with NVAF to the same or greater extent as compared to warfarin, which is a very important clinical advantage of NOAC. Also, it can be concluded that the same or lower frequency of major bleeding, especially intracranial, compared to warfarin, is another important advantage of NOAC versus warfarin. The major advantage of NOAC is their predictable pharmacokinetics and pharmacodynamics, which do not require routine coagulation monitoring, as is the case with warfarin. Also, NOAC have a short half-life in plasma, which is an important advantage in case of overdose and bleeding. The disadvantage of NOAC is that only dabigatran antidote is registered and available on the drug market while rivaroxaban and apixaban are in the research phases. The new generation of oral anticoagulants (dabigatran, rivaroxaban and apixaban) represents significant advances in the prevention of thromboembolic incidents in patients with AF. NOAC showed more advantages than disadvantages compared to warfarin and thus significantly increased the safety of ischemic stroke prevention in patients with AF. |
