Elsevier

The Lancet

Volume 378, Issue 9792, 20–26 August 2011, Pages 713-721
The Lancet

Series
Medical therapy for chronic heart failure

https://doi.org/10.1016/S0140-6736(11)61038-6Get rights and content

Summary

Understanding of contemporary pharmacological therapy for chronic heart failure continues to evolve. In this Review, we discuss how findings from clinical trials have caused the roles of old therapies to be expanded and past treatment algorithms to be challenged. Several trials investigating preserved ejection fraction as a measure of heart failure had disappointing results, although important studies are in progress. Many novel therapeutic approaches for heart failure have emerged and are discussed in this review. The pharmacological treatments for heart failure continue to change, with many exciting possibilities for the future.

Introduction

In the past 40 years, pharmacological therapy for chronic heart failure has rapidly expanded beyond diuretics and digoxin with the serial addition of hydralazine and isosorbide dinitrate, angiotensin-converting enzyme (ACE) inhibitors, β blockers, mineralocorticoid-receptor antagonists, and angiotensin-receptor blockers. The role of early standard therapies, diuretics and digoxin, has changed as new approaches have developed; similarly, contemporary medical therapy for heart failure is evolving. We discuss the controversies that have been incited by emerging data and assess the development of drugs for both heart failure with reduced left ventricular ejection fraction and heart failure with preserved ejection fraction. Additionally, we briefly describe new therapies that extend or address new approaches.

Section snippets

New data for existing agents

Neurohormonal antagonists are key to pharmacological management of patients with impaired ventricular systolic function and symptoms of heart failure. Agents that block the renin-angiotensin-aldosterone system and sympathetic nervous system have substantially improved morbidity and mortality rates in these patients.1, 2 This benefit has been established in adequately sized trials2 that assess the effects of these drugs on major clinical outcomes. Nevertheless, rates of morbidity and mortality

Pharmacological treatment of heart failure with preserved ejection fraction

Whether heart failure with preserved ejection fraction represents a continuum of molecular, cellular, and histochemical derangements compared with heart failure with reduced ejection fraction has been debated. However, the condition is now accepted as a disease entity in its own right, and is affected by concomitant disorders such as hypertension, obesity, and diabetes.26 Despite improved understanding of the pathophysiology of this disorder, pharmacological treatment (in addition to active

Neurohormonal blockade

The effect of neurohormonal blockade on the treatment of heart failure has been profound. Pharmacological challenges delayed the development of orally bioavailable renin inhibitors, despite renin's primary role in the renin-angiotensin-aldosterone system. The ALOFT study36 investigated the effects of addition of an oral, direct renin inhibitor to an ACE inhibitor in 302 patients with chronic heart failure.36 Aliskiren treatment significantly lowered concentrations of NT-proBNP compared with

Conclusions

Clinical trials have provided important guidance for how to maximise the benefits of established therapies in the treatment of patients with systolic chronic heart failure. Yet effective therapies for patients with heart failure with preserved ejection fraction are elusive. The emergence of several new treatment approaches provides encouragement that effective, clinically important therapies will be added in the near future. However, advances in clinical trial design will need to accompany

Search strategy and selection criteria

We searched the Cochrane Library, Medline, and Embase databases, with the search term “heart failure” in combination with the term “drug therapy”, and limited the results to include only adult populations, when available. We largely selected publications in the past 3 years, but did not exclude commonly referenced and highly regarded older publications. We also searched the reference lists of articles identified by this search strategy, and presentations from major international

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