Beta-blockers in chronic heart failure: What have we learned? What do we still need to know?
Introduction
The use of β-blockers for the treatment of chronic heart failure (CHF) has quite literally been a revolution in pharmacological therapy for this condition. These agents had long been contraindicated in the treatment of patients with systolic heart failure, the clinical consequence of impaired myocardial contractile function. However, in the late 1970s and early 1980s, Swedish researchers tested the hypothesis that blockade of chronic sympathetic activation might, in fact, be beneficial in this setting. Decades later, we now have an extensive clinical trials database demonstrating the benefit of these agents in improving prognosis, reducing hospitalisation and, particularly in more severe cases, relieving symptoms (Table 1). This database of placebo-controlled β-blocker trials in CHF is now more extensive than that for angiotensin-converting enzyme (ACE) inhibitors, which are widely accepted as standard therapy for heart failure. The robustness of this data is reflected within current heart failure guidelines, which mandate the use of β-blockers (if tolerated) in patients with mild, moderate and severe symptoms of systolic heart failure, provided the patient has been stabilised and rendered euvolemic (i.e. normal volume status restored).
This review focuses on reported advances in our understanding of β-blocker therapy for CHF. The question is also posed as to what further research is required both to provide additional mechanistic insight into the beneficial effects of these agents and to fill in the remaining gaps in the clinical trials database of β-blockers in this setting.
Section snippets
Sub-group analysis of major heart failure trials
Although there have been no major β-blocker CHF trials published in the past 12–18 months, additional insight has been gained from sub-group analysis of recent large-scale heart failure trials (Table 1). In many cases, these were predefined sub-group analyses, although some post-hoc analyses have also been performed. Sub-group analysis must be interpreted with considerable caution, as patients are generally not randomised within these sub-groups. Nevertheless, these analyses do have the
What do we still need to know?
Despite overwhelming evidence in support of the clinical efficacy of β-blockers in CHF, together with the most recent advances in data (as presented above), there still remain significant gaps in our knowledge of these agents. Thus, there is a clear need for ongoing research to address unanswered questions and to tease out the mechanisms of benefit of β-blockers to better direct therapies in the future.
Conclusions
β-blockers have been a major advance in the pharmacological management of the heart failure patient, and are a tribute to the persistence and mechanistic mind-thought of an early group of Swedish pioneers. They have, however, been slow to be embraced by physicians, particularly because of the ‘baggage’ of the past regarding perceived contraindications in this setting. Furthermore, there remain fears surrounding the tolerability and adverse effects of initiation of these agents, which have
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
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of special interest
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of outstanding interest
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