New antiarrhythmic drugs for atrial fibrillation: focus on dronedarone and vernakalant.
The prevalence of atrial fibrillation (AF) is forecast to rise to 2-5% of the general population by 2050. Of the two fundamental treatment strategies for AF management, rhythm control is the approach which is generally preferred for active, symptomatic, and/or younger patients, whereas rate control is all that is found necessary in the more elderly, sedentary, asymptomatic individual. In many cases, at neither extreme, there remains a genuine choice of therapy, and for those patients, antiarrhythmic strategies would be preferred if effective and safe antiarrhythmic medications were available. Many new antiarrhythmic agents exploiting new mechanisms of action or novel combinations of established antiarrhythmic activity are currently being investigated. Agents which selectively inhibit ion channels specifically involved in atrial repolarization, so-called atrial repolarization delaying agents, are widely acknowledged as potentially ideal antiarrhythmic treatments, as they will probably be both effective and safe, at the very least (free of pro-arrhythmic effects at the ventricular level). Modified analogues of traditional antiarrhythmic drugs with different combinations of ion channel and receptor blocking effects, novel mechanisms of action, and less complicated metabolic profiles are also under development. Completely innovative antiarrhythmic agents with new antiarrhythmic mechanisms, such as stretch receptor antagonism, sodium calcium exchanger blockade, late sodium channel inhibition, and gap junction modulation are also being explored. In addition, there is increasing evidence in support of the antiarrhythmic action of non-antiarrhythmic drugs. Treatments with statins, omega-3 fatty acids, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and aldosterone antagonists are all potentially valuable, over and above any effect related to the treatment of underlying heart disease.
Division of Cardiac & Vascular Sciences, St George's University of London, Cranmer Terrace, London, SW17 0RE, UK. jcamm@sgul.ac.uk
A John
AJ
Camm
Irina
I
Savelieva
D000638:Amiodarone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000840:Anisoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D016275:Atrial Function / Q000187:drug effects; D000077764:Dronedarone; D006801:Humans; D011759:Pyrrolidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000840:Anisoles; D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; C524581:vernakalant; D000077764:Dronedarone; D000638:Amiodarone