Beta-blockers for heart failure--time to think the unthinkable?

Abstract

Heart failure accounts for 5% of acute medical admissions in the UK and its incidence is rising as the population ages.1 The natural history is characterized by inexorable progression, with a steady attrition of patients from terminal pump failure or sudden death. Despite wider and earlier use of angiotensin-converting-enzyme (ACE) inhibitors, the outlook remains poor, with 40–50% mortality within 5 years among patients suffering from mild-to-moderate heart failure, rising to 70–80% in more advanced heart failure.2 The notion that β -blockers may confer substantial prognostic benefits in chronic heart failure will seem counterintuitive and even inconceivable to generations of clinicians brought up with the strict doctrine that these agents are harmful to patients with impaired ventricular function. Nevertheless, a compelling weight of evidence now supports such a radical and unprecedented U-turn in clinical practice. This evidence has emerged in three distinct phases: early reports and hypothesis-generating studies, followed by medium-sized randomized trials and most recently, definitive mortality trials. The traditional dogma that β -adrenoceptor antagonists worsen heart failure was first questioned by Waagstein in 1975.3 Over the next decade, a succession of small studies appeared to confirm that β -blockers are tolerated in over 90% of patients with stable chronic heart failure if introduced gradually, and result in consistent improvements in left ventricular function, haemodynamic indices and exercise tolerance.4 Furthermore, post hoc analysis of secondary prevention trials after myocardial infarction indicated that the prognostic benefits of β -blockade were greatest among those patients with evidence of left ventricular dysfunction.5 These encouraging findings initially attracted little interest, as they flew in the face of a traditional `haemodynamic' model of the pathogenesis of heart failure which emphasized the primacy of mechanical factors (impaired pump function, vasoconstriction and fluid retention). However, such a paradigm could not account for …