New oral anticoagulant drugs in atrial fibrillation and acute coronary syndrome

Abstract

After an acute coronary syndrome, patients remain at risk of recurrent ischemic events despite the use of antiplatelet therapy. In order to reduce the risk of recurrent ischemia in the treatment of patients with acute coronary syndromes, standard oral anticoagulants, such as vitamin K antagonists, have been introduced. These drugs have an important role in preventing stroke and systemic embolism in patients with atrial fibrillation. Vitamin K antagonists (e.g., warfarin) reduce the risk of recurrent cardio­vascular events and stroke but increase the risk of bleeding. In addition, the traditional anticoagulants have other significant drawbacks. Therefore, modulation of the coagulation process represents an important target in the development of new oral anticoagulants today. The new oral anticoagulants selectively target thrombin (dabigatran etexilate) or factor Xa (rivaroxaban, apixaban, edoxaban). Unlike traditional anticoagulants, these drugs have rapid onset of action and a relatively wide therapeutic range, do not require routine prothrombin time (PT) monitoring and have low potential for food and drug interaction. Dabigatran etexilate and rivaroxaban have been already approved in many countries for the prevention of stroke and systemic embolism in patients with atrial fibrillation. The third phase of clinical studies in which rivaroxaban was investigated in patients with acute coronary syndrome has been successfully completed. .

Nakon akutnog koronarnog sindroma, kod bolesnika postoji povećan rizik od rekurentnih ishemičnih događaja, uprkos primeni antiagregacione terapije. U cilju smanjenja rizika od rekurentne ishemije, u terapiju visokorizičnih bolesnika sa akutnim koronarnim sindromom uvode se standardni oralni antikoagulansi, kao što su antagonisti vitamina K. Ovi lekovi imaju važnu ulogu u prevenciji moždanog udara i sistemskog embolizma kod bolesnika sa atrijalnom fibrilacijom. Antagonisti vitamina K (varfarin) smanjuju rizik od nastanka ponovnih kardiovaskularnih događaja i moždanog udara, ali povećavaju rizik od krvarenja. Pored toga, antagonisti vitamina K poseduju i druge, značajne nedostatke, tako da modulacija procesa koagulacije danas predstavlja značajnu metu za razvoj novih oralnih antikoagulanasa. Novi oralni antikoagulansi deluju selektivno na trombin (dabigatran eteksilat) ili na faktor koagulacije Xa (rivaroksaban, apiksaban, edoksaban). Za razliku od standardnih antikoagulanasa, imaju brz početak dejstva i relativno veliku terapijsku širinu, ne zahtevaju laboratorijsku kontrolu protrombinskog vremena (PT) i retko stupaju u interakcije sa hranom i lekovima. Dabigatran eteksilat i rivaroksaban su već registrovani u mnogim zemljama za prevenciju moždanog udara i sistemskog embolizma kod bolesnika sa atrijalnom fibrilacijom. Treća faza kliničke studije u okviru koje je ispitivan rivaroksaban kod bolesnika sa akutnim koronarnim sindromom uspešno je završena. .