Hemodynamic effects of BTS 49465, a new long-acting systemic vasodilator drug, in patients with severe congestive heart failure

The hemodynamic effects of BTS 49465, a new oral, direct-acting systemic vasodilator drug, were investigated in 10 patients with severe chronic congestive heart failure. One to 2 hours after the administration of 1.5 mg/kg orally, BTS 49465 produced significant increases in cardiac index, stroke volume index, and stroke work index (26%, 27%, and 23%, respectively, p < 0.01 to 0.001) and marked decresses in left ventricular filling pressure (-12.6 mm Hg, 44%), mean pulmonary artery pressure (-13.2 mm Hg, 31%), and mean right atrial pressure (-7.7 mm Hg, 63%), all p < 0.001, without significant changes in heart rate. These hemodynamic responses were accompanied by notable declines in systemic vascular resistance (-28%, p < 0.001) and pulmonary arteriolar resistance (-24%, p < 0.05). These effects persisted throughout the 24-hour period of observation. The decline in left ventricular filling pressure in our patients ranged in magnitude from 8 to 21 mm Hg, and varied linearly and directly with pretreatment values for left ventricular filling pressure (r = 0.69). The decrease in systemic vascular resistance ranged in magnitude from 3% to 40% and varied linearly and directly with pretreatment values for systemic vascular resistance (r = 0.85). These data indicate that BTS 49465, a new oral, direct-acting vasodllator agent, exerts balanced cardiocirculatory effects in patients with severe chronic heart failure, which may be sustained with once-dally oral administration.