With beta-blockers as the exception, increasing doubt is emerging on the value of
antiarrhythmic drug therapy following a series of trials that have either shown no mortality benefit or even an excess mortality. Vaughan Williams class I drugs are generally avoided in patients with structural
heart disease, and class IV drugs are avoided in
heart failure. Unfortunately, arrhythmias are a growing problem due to an increase in the incidence of
atrial fibrillation and
sudden death. The population is becoming older and more patients survive for a longer time period with
congestive heart failure, which again increases the frequency of both supraventricular as well as ventricular arrhythmias. Class III
antiarrhythmic drugs act by blocking repolarising currents and thereby prolong the effective refractory period of the myocardium. This is believed to facilitate termination of re-entry
tachyarrhythmias. This class of drugs is developed for treatment of both supraventricular and ventricular arrhythmias.
Amiodarone,
sotalol,
dofetilide, and
ibutilide are examples of class III drugs that are currently available.
Amiodarone and
sotalol have other antiarrhythmic properties in addition to pure class III action, which differentiates them from the others. However, all have potential serious adverse events. Proarrhythmia, especially
torsade de pointes, is a common problem making the benefit-risk ratio of these drugs a key question. Class III drugs have been evaluated in different settings: primary and
secondary prevention of ventricular arrhythmias and in treatment of
atrial fibrillation or flutter. Based on existing evidence there is no routine indication for
antiarrhythmic drug therapy other than beta-blockers in patients at high risk of
sudden death. Subgroup analyses of trials with
amiodarone and
dofetilide suggest that patients with
atrial fibrillation may have a mortality reduction with these drugs. However, this needs to be tested in a prospective trial. Similarly, subgroups that will benefit from prophylactic treatment with class III
antiarrhythmic drugs may be found based on QT-intervals or - in the future - from genetic testing. Class III drugs are effective in converting
atrial fibrillation to sinus rhythm and for the maintenance of sinus rhythm after conversion. This is currently by far the most important indication for this class of drugs. As defined by recent guidelines,
amiodarone and
dofetilide have their place as second-line
therapy except for patients with
heart failure where they are first line
therapy being the only drugs where the safety has been documented for this group of high risk patients.