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Efficacy and safety of flosequinan, given over 3 days, evaluated by continuous hemodynamic monitoring
A Schneeweiss1, M Plich, T Green
1Geriatric Cardiology Research Foundation, Safed, Israel.
Insights
Flosequinan, a balanced vasodilator, significantly improved hemodynamics in patients with chronic congestive heart failure. This cardiac drug demonstrated sustained efficacy over three days, enhancing cardiac output and reducing pulmonary capillary wedge pressure.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Chronic congestive heart failure (CHF) is a debilitating condition characterized by impaired cardiac function.
- Current treatments for CHF often involve diuretics and digitalis, but balanced vasodilators offer potential for improved hemodynamic management.
Purpose of the Study:
- To evaluate the hemodynamic effects of flosequinan, a novel balanced vasodilator, in patients with chronic congestive heart failure.
- To assess the acute and sustained hemodynamic response to oral flosequinan administration.
Main Methods:
- A study involving 12 patients with chronic congestive heart failure.
- Patients received 100 mg of flosequinan orally, once daily for three days, in addition to their existing diuretic and digitalis therapy.
- Hemodynamic monitoring, including pulmonary capillary wedge pressure (PCWP) and cardiac output (CO), was conducted for 72 hours post-administration.
Main Results:
- Flosequinan significantly reduced PCWP and increased CO within 1-2 hours of administration on all three days (p < 0.05).
- Hemodynamic improvements were sustained for at least 24 hours after each dose, with significant effects observed at 72 hours.
- Systemic and pulmonary vascular resistances were significantly reduced, with only a slight increase in heart rate observed transiently.
Conclusions:
- Flosequinan effectively produces hemodynamic improvement in patients suffering from chronic congestive heart failure.
- The drug demonstrated consistent efficacy with repeated dosing, suggesting a reliable therapeutic option for managing CHF hemodynamics.
Abstract:
The hemodynamic effects of flosequinan, a new balanced vasodilator, were evaluated in 12 patients with chronic congestive heart failure. The drug was added to diuretics and digitalis and given as an oral dose of 100 mg, once daily in the morning, over 3 days, and hemodynamic monitoring was performed before the first dose and for 72 h thereafter. Hemodynamic improvement, peaking between 1 and 2 h after oral administration, was observed on all 3 days. On day 1 pulmonary capillary wedge pressure (PCWP) was reduced from 27.8 +/- 8.6 to 13.0 +/- 3.1 mm Hg and cardiac output (CO) increased from 3.3 +/- 0.6 to 4.5 +/- 0.9 liters/min (p less than 0.05). After 12-16 h the effect was slightly attenuated but remained significant at 24 h. A similar response was observed after the doses given on days 2 and 3. At 72 h PCWP was 15.5 +/- 4.1 mm Hg and CO 3.8 +/- 1.1 liters/min (p less than 0.05 for the difference from baseline). Heart rate was slightly increased only at 2 h after the dose. Pulmonary arterial and right atrial pressure and systemic and pulmonary vascular resistances were significantly reduced (except for systemic resistance at 72 h). In conclusion, flosequinan produces hemodynamic improvement in patients with chronic congestive heart failure. The response to subsequent doses is similar to the response to the first dose.