Author + information
- Received January 22, 1993
- Revision received March 12, 1993
- Accepted March 31, 1993
- Published online October 1, 1993.
- Stephen S. Gottlieb, MD, FACC∗∗,
- Marrick L. Kukin, MD, FACC∗,
- Joshua Penn, MD∗,b,
- Michael L. Fisher, MD, FACC∗,
- Michelle Cines, RN∗,
- Norma Medina, RN∗,
- Madeline Yushak, RN∗,
- Mary Taylor, RN∗ and
- Milton Packer, MD, FACC∗
- ↵∗Address for correspondence: Stephen S. Gottlieb, MD, Division of Cardiology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, Maryland 21201.
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−5and heart rate increased by 4 ± l 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/mn per m2and 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.
☆ This work was supported by a grant from Boots Pharmaceuticals, Inc., Lincolnshire, Illinois.
- Received January 22, 1993.
- Revision received March 12, 1993.
- Accepted March 31, 1993.