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(Circulation. 2002;105:2223.)
© 2002 American Heart Association, Inc.

Clinical Cardiology: New Frontiers

New Therapeutic Options in Congestive Heart Failure

Part II

John McMurray, MD, FRCP, FESC; Marc A. Pfeffer, MD, PhD

From the Clinical Research Initiative in Heart Failure, University of Glasgow, Scotland (J.M.), and the Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass (M.A.P.).

Correspondence to Dr John J.V. McMurray, Clinical Research Initiative in Heart Failure, University of Glasgow, Wolfson Building, Glasgow G12 8QQ, Scotland. E-mail J.McMurray@bio.gla.ac.uk

Key Words: diastole • heart failure • pharmacology • trials • molecular biology

	Introduction

 
The second part of this review deals with newer, nonneurohumoral, pharmacological approaches to congestive heart failure (CHF) and nonpharmacological interventions in heart failure patients with low left ventricular ejection fraction (LVEF) as well as potential treatments for CHF with preserved LV systolic function. An algorithm summarizing current, evidence-based therapy is also provided.

	Anticytokine and Immunomodulating Therapy

 
Cytokines, such as tumor necrosis factor, are produced in increased amounts in a variety of tissues in patients with CHF.¹ Higher plasma cytokine concentrations are associated with a worse prognosis.¹ Experimentally, cytokines depress myocardial contractility, cause myocyte death, and induce heart failure.¹ There is some evidence that anticytokine interventions improve ventricular function and clinical status in CHF.^2,3 Two parallel trials (Randomized Etanercept North American Strategy to Study Antagonism of Cytokines [RENAISSANCE] and Research into Etanercept Cytokine Antagonism in Ventricular Dysfunction Trial [RECOVER], pooled as the Randomized Etanercept Worldwide Evaluation [RENEWAL] program) examining the effect of the anti–tumor necrosis factor agent etanercept on morbidity and mortality in CHF, however, were recently discontinued because of futility (Table). Even more recently, a placebo-controlled phase II trial with an alternative anti–tumor necrosis factor chimeric monoclonal antibody, infliximab, was stopped early because of higher rates of mortality and hospitalization in the active-therapy group. Whether this means that the cytokine hypothesis is invalid, that etanercept and infliximab were the wrong drugs to use (or were used incorrectly), that inappropriate patients were chosen, or that the study designs were flawed is unknown.

View this table: [in this window] [in a new window]   Table 1. Ongoing and Planned Trials of Pharmacological Agents in CHF

	Matrix Metalloproteinase Inhibitors

 
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