Clinical and Hemodynamic Effects of Nesiritide (B-Type Natriuretic Peptide) in Patients With Decompensated Heart Failure Receiving Beta-Blockers

William T. Abraham, MD; Mei L. Cheng, PhD; Geraldine Smoluk, PhD

Disclosures

CHF. 2005;11(2):59-64. 

In This Article

Abstract and Introduction

The use of β blockers in congestive heart failure presents a therapeutic challenge for patients with acute episodes of decompensation. Such patients may be less responsive to positive inotropic agents, whereas the beneficial effects of nesiritide, which are not dependent on the β-adrenergic receptor signal-transduction pathway, may be preserved. This analysis of the Vasodilation in the Management of Acute CHF trial evaluated the safety and efficacy of nesiritide in decompensated congestive heart failure patients receiving β blockers. The Vasodilation in the Management of Acute CHF trial was a multicenter, randomized, controlled evaluation of nesiritide in 489 hospitalized patients with decompensated congestive heart failure. One hundred twenty-three patients were on chronic β-blocker therapy at enrollment (31 randomized to placebo, 50 to nesiritide, and 42 to nitroglycerin). Primary end points included pulmonary capillary wedge pressure and dyspnea evaluation at 3 hours. Patients receiving nesiritide, but not IV nitroglycerin, had significantly reduced pulmonary capillary wedge pressure vs. placebo at 3 hours regardless of β-blocker use. The use of β blockers did not alter the beneficial effects of nesiritide on systemic blood pressure, heart rate, or dyspnea evaluation. In nesiritide-treated subjects, safety profiles were similar regardless of β-blocker use. Thus, the clinical and hemodynamic benefits and safety of nesiritide are preserved in decompensated congestive heart failure patients receiving chronic β blockade.

The demonstrated benefits of β blockers in patients with congestive heart failure (CHF) have led to greater use of these drugs over the past few years.[1] Recently published clinical practice guidelines for the evaluation and management of chronic heart failure mandate the use of these agents in nearly all CHF patients with systolic dysfunction.[2] Beta blockers are also prescribed commonly for the treatment of CHF associated with preserved left ventricular systolic function, also called diastolic heart failure. While improving morbidity and mortality in chronic heart failure,[3—5] β blockers present a challenge when CHF patients present with acute decompensation requiring IV vasoactive therapy. Clinical evidence suggests that β blockade should not be abruptly discontinued in heart failure patients.[6] It is likely, however, that β blockers attenuate the positive inotropic effects of sympathomimetic agents (e.g., dobutamine), which rely on the β-adrenergic receptor signal-transduction pathway to produce clinical and hemodynamic benefits.[] Moreover, the use of β1-selective adrenergic blockers in combination with dobutamine may increase the likelihood of (unmasked) β2-receptormediated hypotension.[8]

Nesiritide (Natrecor, Scios Inc., Sunnyvale, CA) is the first approved agent in a new pharmacologic class of drugs, the natriuretic peptides. It is a recombinant form of human B-type natriuretic peptide, an endogenous peptide secreted primarily by the cardiac ventricles in response to ventricular wall stress (pressure or volume overload).[9—12] In clinical trials, nesiritide added to standard care has been found to improve dyspnea, decrease afterload and preload, increase cardiac output, promote natriuresis and diuresis, and suppress sympathetic activation, endothelin, and the reninangiotensin- aldosterone system in CHF patients.[13—17] The physiologic and pharmacologic effects of nesiritide are mediated via the guanylyl cyclase-A receptor, a β-adrenergic-independent pathway.[18] Because nesiritide does not require β-adrenergic receptors or any component of the β-adrenergic receptor signal-transduction pathway for its pharmacologic effects, we postulated that the clinical and hemodynamic benefits as well as safety of nesiritide in patients with acutely decompensated heart failure should be similar regardless of β-blocker treatment status.

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