Abstract
Ventricular arrhythmias such as sustained ventricular tachycardia and ventricular
fibrillation account for two thirds of sudden cardiac deaths. Most ventricular tachyarrhythmias
have well understood mechanisms such that it is theoretically possible to conceive
of an antiarrhythmic drug-based intervention that would prevent arrhythmias that cause
sudden cardiac death. Pharmaceutical agents which interfere with ion channel activity
are known as antiarrhythmic drugs.
Acute experiments showing antiarrhythmic effects in the basic science laboratory have
often not translated into clinical effectiveness. Evidence of efficacy has been difficult
to assess and appears to be sparse. However, proarrhythmia is common and complicates
assessment of the potential value of antiarrhythmic drugs. Important studies such
as the Cardiac Arrhythmia Suppression Trial and the Survival With ORal d-sotalol study confirmed that antiarrhythmic drugs could kill rather than cure patients
at risk of sudden cardiac death, and spelled the death knell for widespread use of
antiarrhythmic drugs for the primary prevention of sudden cardia death in high risk
patients.
However, when the implantable cardioverter defibrillator was introduced into clinical
practice the situation changed - a drug that generally suppressed ventricular tachyarrhythmias
was needed, but safety concerns were alleviated because the ICD could reverse proarrhythmic
adverse effects. The accent changed towards the development of drugs that might reduce
the prevalence or the symptomatic burden of ventricular arrhythmias. Similarly, antiarrhythmic
drug development progressed towards finding an agent that might reduce symptoms associated
with recurrent atrial fibrillation rather than for the treatment of ventricular arrhythmia.
In recent times the goal of antiarrhythmic therapy has changed again. No longer is
it thought necessary to develop blockbuster therapies, but to concentrate on the specific
mechanisms of cardiac arrhythmias in individuals and to develop therapies that can
be specifically engineered to help carefully defined phenotypes. Personalised or precision
medicine is now guiding the development of antiarrhythmic agents that are directed
to very specific targets and arrhythmia mechanisms and are without off-target effects
that may compromise their efficacy.
The value of antiarrhythmic medical therapy has raised great hopes which have been
followed by disillusionment. Now hopes and needs are rising again, and we are better
prepared to make this therapy successful. If we understand the arrhythmias we may
be able to design effective and uncomplicated therapy.
Keywords
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Publication history
Published online: March 18, 2017
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