Acute and long-term effects of flosequinan in patients with chronic cardiac failure

The acute and long-term effects of the orally active vasodilator flosequinan were assessed in 10 patients with New York Heart Association class II to IV cardiac failure. Baseline hemodynamics, exercise capacity, left and right ventricular ejection fraction, and pulmonary transit time were measured by right cardiac catheterization, bicycle ergometer stress testing, and nuclear angiocardiography during a run-in period on placebo. Acute hemodynamic effects of flosequinan were monitored for 48 hours; the drug was then given as a single 100 mg daily dose for 6 weeks. Exercise capacity was reevaluated every 2 weeks, and right cardiac catheterization and nuclear angiocardiography were repeated at the end of the 6-week period. Placebo did not exert any effect. Flosequinan reduced right atrial, pulmonary artery, and pulmonary artery wedge pressures from 60 minutes to 48 hours after dosing. Heart rate was minimally increased. Cardiac index, mean systemic arterial pressure, and systemic and pulmonary vascular resistance were substantially unaffected. These effects were maintained after 6 weeks. Exercise capacity was enhanced after 2, 4, and 6 weeks. Left ventricular ejection fraction was unchanged, whereas right ventricular ejection fraction and pulmonary transit time were improved. In conclusion, flosequinan exerted a potent, long-lasting, venodilating effect that was maintained long-term, without evidence of tolerance.