Added Benefit of Mineralocorticoid Receptor Blockade in the Primary Prevention of Sudden Cardiac Death

Abstract

Sudden cardiac death (SCD) is a major public health issue. In patients with heart failure (HF) of various origins, including ischemia post-myocardial infarction (MI), successful development of pharmacological therapies that target neurohormonal abnormalities and modulate disease progression has changed the major cause of death from progressive pump failure to SCD from cardiac arrhythmias. Conditions such as hypertension, hypertrophic cardiomyopathy, aortic stenosis, diabetes mellitus, and aging are accompanied by hypertrophy and fibrosis, increasing the risk of SCD. Also affected are patients with inherited arrhythmogenic disorders such as long-QT syndrome and Brugada syndrome (BrS). Although the mechanisms responsible for SCD, its epidemiology, and treatment have recently been reviewed,1–4 1 aspect of therapy that deserves further emphasis for the prevention of SCD is the role of aldosterone blockade (AB) or, more precisely, mineralocorticoid receptor blockade (MRB). Response by Kloner and Cannom p 2982 As with any pharmacological approach to reduce SCD, including MRB, implantable cardioverter-defibrillators (ICDs) and/or cardiac resynchronization therapy (CRT) will remain central in the secondary prevention of SCD in high-risk individuals. Rather, we hypothesize that MRB may have an important role in the primary prevention of SCD in high-risk individuals both with and without systolic left ventricular dysfunction (SLVD) and as an adjunct to ICDs and/or CRT, both in the primary and secondary prevention of SCD. In this article, we will briefly review the current experience with MRB in the prevention of SCD in patients with severe chronic HF and SLVD and in patients with SLVD and HF post-MI. We will discuss the potential mechanisms by which MRB may reduce SCD. Finally, we will propose opportunities for further reducing SCD in high-risk individuals without SLVD or HF. MRB with spironolactone 12.5 to 50 mg/d was shown to be effective in reducing SCD by 29% ( P =0.02) and total mortality by …