Results of the VMAC Trial: Vasodilation in the Management of Acute Congestive Heart Failure
Objective: To compare the efficacy and safety of nesiritide (B-type or brain natriuretic peptide [BNP]), IV nitroglycerin (NTG), and placebo (PL), when added to standard care (may have included IV diuretics, dobutamine, dopamine, and all chronic cardiac therapy). Methods: This multicenter, randomized, placebo- and active-controlled trial treated 489 hospitalized patients with dyspnea at rest due to acutely decompensated CHF. Patients with acute coronary syndromes, diastolic dysfunction, arrhythmias, or renal insufficiency were not excluded. Randomization was stratified by use of a right heart catheter (n=246) or not (n=243). Patients were randomized to PL (n=142), NTG (n=143), BNP fixed-dose (n=142), or BNP adjustable-dose (n=62; catheterized patients only). BNP was administered as a 2 μg/kg bolus, followed by a fixed-dose infusion of 0.01 μg/kg/min for 3 hours. After 3 hours, adjustable-dose BNP patients could undergo dose increases to a maximum of 0.03 μg/kg/min, and PL patients crossed over to NTG or BNP fixed-dose. NTG dose was determined by the Investigator and was to be titrated to effect. Primary endpoints were the 3 hour pulmonary capillary wedge pressure (PCWP) and subject’s dyspnea evaluation (using a 7-point ordinal scale), comparing BNP to PL. Results: BNP significantly reduced PCWP and all PA pressures, compared to NTG and PL, by 15 minutes and through the 3 hour period. At 3 hours, dyspnea was improved by BNP compared to PL (p=0.034); the change in dyspnea with NTG was not statistically significant (p=0.191).
By 24 hours, symptomatic hypotension occurred in only 4% of BNP patients and 5% of NTG patients, whereas more headache occurred with NTG (20% vs. 8%, p<0.001). Fewer adverse events overall occurred in patients treated with BNP than with NTG (p<0.001). Conclusions:When added to standard care, fixed-dose administration of nesiritide produced a more rapid and greater improvement in hemodynamics than NTG titration or standard care alone (PL). Nesiritide, but not NTG, was associated with significant improvements in dyspnea, compared to standard care alone (PL). Compared to NTG, nesiritide was better tolerated by these acutely ill CHF patients. These data from the VMAC Trial suggest an important role for nesiritide in the treatment of acutely decompensated CHF, with or without invasive monitoring and without the need for dose titration.
- Copyright © 2000 by American Heart Association