Potential of non-antiarrhythmic drugs to provide an innovative upstream approach to the pharmacological prevention of sudden cardiac death.

Sudden cardiac death (SCD) is the most common cause of death and often occurs in low-risk patients. Present prevention strategies, mainly confined to high-risk subjects (proposed implantable cardioverter defibrillators recipients), have a limited effect on SCD burden in the general population. A relatively unexplored strategy for extending SCD prevention could imply targeting the early (upstream) processes of the complex cascade leading to SCD by non-antiarrhythmic drugs (i.e., beta-blockers, aldosterone antagonists, angiotensin-converting enzyme inhibitors, angiotensin receptor-blocker agents, statins and omega-3 fatty acids). In this innovative pharmacological perspective, agents with upstream effects may also be used in high-risk patients in association with a strictly downstream intervention, such as the implantable cardioverter defibrillator, in an attempt to obtain an additive/synergetic effect.