Vasodilation in the Management of Acute Congestive Heart Failure - VMAC


The VMAC trial was a randomized, double-blinded, placebo-controlled trial designed to test the safety and efficacy of intravenous (IV) nesiritide compared to placebo and IV nitroglycerin in the treatment of decompensated congestive heart failure (CHF).


To investigate the efficacy and safety of IV nesiritide in addition to standard medical therapy compared to placebo, specifically with regard to decreasing pulmonary capillary wedge pressure (PCWP) and decreasing self-assessed dyspnea in the nesiritide group compared to placebo.

Study Design

Study Design:

Patients Enrolled: 489
NYHA Class: III-IV in 84% of patients
Mean Follow Up: 6 months
Mean Patient Age: mean of 60, 62, 62 in 3 arms, p=NS
Female: 31
Mean Ejection Fraction: 85% of patients had ejection fractions <40%.

Patient Populations:

Dyspnea at rest due to decompensated CHF severe enough to require hospitalization and IV therapy. A cardiac etiology for dyspnea was established by estimated or measured elevation of cardiac filling pressures (PCWP ≥20 mm Hg in catheterized patients) and at least two of the following: 1) jugular venous distention, 2) paroxysmal nocturnal dyspnea or two-pillow orthopnea within 72 hours before study entry, 3) abdominal discomfort due to mesenteric congestion, or 4) a chest x-ray film consistent with decompensated CHF. Patients receiving dobutamine or dopamine but who otherwise met entry criteria were also permitted into the study.


Systolic blood pressure < 90 mm Hg; cardiogenic shock or volume depletion; contraindication to IV vasodilator; acutely unstable clinical status that would not permit a three-hour placebo period; use of IV nitroglycerin that could not be withheld; mechanical ventilation; and anticipated survival of less than 30 to 35 days. Patients with decompensated CHF in the setting of acute coronary syndromes, preserved systolic function, renal failure, or atrial or ventricular arrhythmias were not excluded based on these conditions alone.

Primary Endpoints:

Comparison of nesiritide versus placebo with regard to:

1) Change in PCWP from baseline in catheterized patients at three hours.

2) Patient self-evaluation of dyspnea at three hours.

Secondary Endpoints:

Comparison of nesiritide and nitroglycerin with regard to: onset of effect on PCWP, effect on PCWP at 24 hours, self-assessed dyspnea and global clinical status, and the overall safety profile, in addition to other clinical and hemodynamic effects at three and 24 hours

Drug/Procedures Used:

1) Patients were stratified by the physician’s nonrandomized preference to use a right heart catheter in treating the patient.

2) For the first three hours after enrollment, noncatheterized patients were randomized to one of three arms: titratable IV nitroglycerin, fixed-dose nesiritide (2 mcg/kg bolus followed by 0.01 mcg/kg/min infusion), or placebo. Catheterized patients were randomized to one of the same three groups or in addition to an adjusted-dose nesiritide subarm.

3) After three hours (primary endpoint), patients assigned to the placebo group crossed over to either the titratable nitroglycerin or fixed dose nesiritide arm.

Concomitant Medications:

Standard medical therapy for heart failure including dopamine or dobutamine, but with the exception of IV vasodilators or inodilators

Principal Findings:

A total of 489 patients were randomized, with 246 in the right heart catheter stratum, and 243 in the noncatheter stratum. There were 143 patients in the nitroglycerin arm, 204 in the nesiritide arm, and 142 in the placebo arm; all patients had dyspnea at rest, and 84% of patients had chronic decompensated CHF (New York Heart Association [NYHA] class III-IV) prior to the acute episode.

At three hours, the mean decrease in PCWP from baseline was -5.8 mm Hg for nesiritide, -3.8 mm Hg for nitroglycerin, and -2 mm Hg for placebo (p<0.001 for nesiritide vs. placebo, p=0.03 for nesiritide vs. nitroglycerin; p=0.09 for nitroglycerin vs. placebo). Also at three hours, nesiritide improved self-reported dyspnea compared to placebo (p=0.03), but not compared to nitroglycerin.

At 24 hours, the mean decrease in PCWP was greater with nesiritide versus nitroglycerin (-8.2 mm Hg vs. -6.3 mm Hg, p=0.04), but there were no differences in self-reported dyspnea (p=0.13). There were similar adverse effects at up to six months, with more reported headaches in the nitroglycerin-treated patients.


When added to standard medical therapy in patients with decompensated CHF, nesiritide was associated with beneficial hemodynamic improvements. Improvements in patient-reported dyspnea that were apparent at three hours were sustained at 24 hours. Nesiritide administration was associated with fewer mild side effects than IV nitroglycerin in this setting, and may be slightly more efficacious than nitroglycerin in its hemodynamic effects.


Publication Committee for the VMAC Investigators (Vasodilatation in the Management of Acute CHF). Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 2002;287:1531-40.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Chronic Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Dobutamine, Pulmonary Wedge Pressure, Dyspnea, Paroxysmal, Human Rights, Heart Failure, Dopamine, Cardiac Catheters, Headache, X-Ray Film, Natriuretic Peptide, Brain, Nitroglycerin

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