PREVENTION OF STROKE IN ATRIAL FIBRILLATION: ARE ALL ORAL DRUGS THE SAME?
Antoni Martinez-Rubio, M.D., Ph.D.,
University Hospital of Sabadell (Univ Autonoma de Barcelona), Sabadell, Spain
Prevention of thromboembolic events using oral anticoagulant drugs (OAC) is mandatory in several patients with atrial fibrillation. Therefore, OAC have been developed and used since decades. However, efficacy of these must be well balanced with the risk of inherent bleeding complications. Dicumarine (DC-D) derivates are useful but need monitoring and show several food and drug interactions, which may be critical. Therefore, novel OAC (NOAC) have been developed.These new drugs interact with two different targets (factor IIa or factor Xa of the coagulation cascade).Actually, the clinical results of four NOACS (dabigatran (DAB), rivaroxaban (RIV), apixaban (API), edoxaban (EDO)) have been presented in four major trials (RELY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) of stroke prevention in atrial fibrillation in comparison with warfarin. Pharmacokinetics and pharmacodynamics of the four NOACS are different. Thus, DAB and API are given twice/daily whereas RIV and EDO have been tested in once daily approach. In addition, renal clearance ranges from 25% with API to 80% with DAB (33% with RIV and 35% with EDO). Furthermore, bioavailability, hours to maximal concentration, CYP metabolism, transporters, protein binding and half-life also differ between NOACS.Thus, plasma levels of NOACs may influence and also be influenced by some drugs, which are often used (e.g. diltiazem, amiodarone, etc.).Therefore, physicians need to know the main results of the four major clinical trials, those of important sub-studies and also the major differences between the four NOACS in order to manage properly the stroke preventive strategies of patients with atrial fibrillation. In addition, since NOACs have been used in different dosages during the trials, physicians should know which populations do benefit of low or high dosages of the NOACs and how to manage complications. In resume, NOACs demonstrate several advantages over DC-D but physicians need to know how to implement treatment with these new drugs and which are the main results and characteristics of all of them.