A jódmentes szintetikus amiodaron-kongéner dronedaron odüsszeája: az antiarrhythmiás gyógyszerfejlesztés szürke fejezete

Absztrakt

Dronedarone is a novel synthetic noniodinated benzofuran derivative that has been developed to eliminate the adverse effects of the most effective and commonly used antiarrhythmic drug, amiodarone. Dronedarone’s electrophysiological spectrum is largely similar to that of ’multichannel’ inhibitor//multitarget amiodarone. Some prospective, randomized, controlled clinical trials (DAFNE, EURIDIS/ADONIS, ERATO, ATHENA) have already suggested safety (low proarrhythmic potential, and lack of organ toxicity), sinus rhythm maintaining and/or ventricular rate controlling efficacy of dronedarone (800 mg/day). Opposing these, ANDROMEDA and PALLAS trials raised safety concerns for patients with systolic/congestive heart failure (CHF) and severe left ventricular dysfunction (LVEF ≤ 35%; NYHA III-IV) by doubling the cardiovascular mortality. Dronedarone could be useful second- or third-line agent for some of low-risk symptomatic intermittent (paroxysmal/persistent) AF patients who require rhythm control. Despite the fact that dronedarone does not contain iodine, there were reported severe liver injuries (in some cases requiring urgent liver transplantation) and lung toxicity. Dronedarone should not be used for patients with CHF, those with left ventricular dysfunction (LVEF ≤ 35%) and/or permanent AF. Subsequent and pooled indirect (meta)analyses showed increased all-acuse and cardiovascular mortality and expanding heart failure exacerbations while using dronedarone accross wide groups of populations. Until now, dronedarone’s place in the management of AF remained largely undefined and in the grey zone, primarily because of its relative lack of efficacy and safety. The whole dronedarone scenario thus far is an example of enthusiasm surpassing the evidence based concerns and one has to struggle to find a low-risk atrial fib population/patient where it would be more effective instead of being more unsafe. New pharmacotherapeutic options are needed urgently.