Sustained hemodynamic response to flosequinan in patients with heart failure receiving angiotensin-converting enzyme inhibitors

Abstract

Objectives: We evaluated the short- and long-term effects of flosequinan in 47 patients with severe heart failure despite ongoing captopril treatment.

Background: There have been no previous evaluations of the long-term hemodynamic effects of any direct-acting vasodilator in patients with heart failure receiving an angiotensin-converting enzyme inhibitor. Flosequinan is an arterial and venous vasodilator with actions similar to those of the hydralazine-isosorbide dinitrate combination.

Methods: After baseline hemodynamic measurements using balloon-tipped pulmonary artery and radial arterial catheters, patients were randomized to receive 50, 100 or 150 mg of flosequinan daily. Hemodynamic variables were measured immediately before and after short-term flosequinan administration and after 8 weeks of therapy.

Results: With short-term flosequinan administration, mean arterial, right atrial and left ventricular filling pressures decreased by 6.4 +/- 1.1, 3.8 +/- 0.5 and 7.3 +/- 0.7 mm Hg, respectively (all p < 0.001). Cardiac index increased by 0.5 +/- 0.1 liters/min per m2, systemic vascular resistance decreased by 616 +/- 105 dynes.s.cm-5 and heart rate increased by 4 +/- 1 beats/min (all p < 0.001). After 8 weeks of long-term flosequinan administration, the vasodilator effect of a dose of flosequinan persisted. Compared with pretreatment baseline values, mean arterial, right atrial and left ventricular filling pressures at the peak effect of flosequinan were decreased by 3.5 +/- 1.3, 2.8 +/- 0.7 and 5.1 +/- 1.3 mm Hg, respectively (all p < 0.01). Systemic vascular resistance had decreased by 585 +/- 95 dynes.s.cm-5, cardiac index had increased by 0.5 +/- 0.1 liters/min per m2 and heart rate had increased by 10 +/- 2 beats/min (all p < 0.001).

Conclusions: The arterial and venous vasodilator flosequinan exerts both short- and long-term sustained hemodynamic effects in patients with heart failure receiving angiotensin-converting enzyme inhibitors.