Beta-adrenergic blockade 2002: a pharmacologic odyssey in chronic heart failure

The treatment for heart failure has evolved considerably during the past two decades. Initially focused on hemodynamic derangement, diuretics and vasodilator agents were employed for symptomatic management. Beta blocking agents, with intrinsic negative inotropic activity, were considered specifically contraindicated. Neurohormonal activation subsequently became recognized and validated as a self-perpetuating influence on chronic heart failure and progressive adverse ventricular remodeling. Antagonism of the renin-angiotensin-aldosterone axis produced significant survival benefits in chronic heart failure populations. Concomitant intense sympathetic nervous system activation remained an additional therapeutic target. Pathophysiologic insights revealed a biologically plausible framework for the use of beta blocking agents in heart failure. This review summarizes the major clinical trials of beta blockers in heart failure populations with systolic left ventricular dysfunction. These trials support the integration of beta blockade as a critical component of standard therapy for chronic heart failure. Ongoing trials and unresolved issues are also discussed.