We studied the hemodynamic effect of a single dose of the new direct-acting
vasodilator,
flosequinan, in 25 patients with severe acute-onset
heart failure complicating acute
myocardial infarction, which was resistant to high doses of
diuretics,
nitrates and
dobutamine given intravenously.
Flosequinan was added to conventional
therapy within 3.7 +/- 0.8 days of the
infarction in the form of a single oral dose of 100 mg. Hemodynamic monitoring was performed every hour for 4 hours after the administration, without any other
drug being added.
Flosequinan produced hemodynamic improvement in all patients. The effect peaked at 1 to 2 hours and remained at this level at 4 hours. Pulmonary capillary wedge pressure decreased from 28.4 +/- 4.5 to 17.8 +/- 5.7 mmHg and cardiac output increased from 3.5 +/- 0.3 to 4.0 +/- 0.4 L/min (p less than 0.05 for both). Pulmonary arterial and pulmonary vascular resistances were also significantly reduced. Heart rate was not significantly altered. Mean systemic arterial pressure was slightly but not significantly reduced. Administration of
flosequinan was not associated with symptomatic
hypotension,
cardiac arrhythmias or other adverse events and the hemodynamic effect was not related to the pre-treatment serum
sodium concentration. We conclude that
flosequinan is effective in producing acute hemodynamic improvement in patients with
heart failure complicating acute
myocardial infarction which is resistant to conventional
therapy.
Flosequinan is well tolerated in this group of patients and therefore further studies to determine the duration of action of the
drug in this condition are appropriate.