Effects of long-term therapy with oral piroximone on resting hemodynamics, peak aerobic capacity, and the anaerobic threshold in patients with heart failure.

Piroximone (MDL 19205), a new imidazole derivative with positive inotropic and vasodilating properties, was administered to 10 patients with congestive heart failure. After acute intravenous (0.90 +/- 0.12 mg/kg, mean +/- SEM) and oral (1.41 +/- 0.18 mg/kg) administration, cardiac index and stroke volume index increased and were accompanied by a decline in systemic vascular resistance, pulmonary capillary wedge pressure, and right atrial pressure. Mean arterial pressure was unchanged, but heart rate increased modestly after intravenous piroximone. An increase in premature ventricular contractions was documented in four patients after drug administration. Seven of the 10 patients completed 12 weeks of therapy with piroximone; one patient withdrew after 8 weeks because of deterioration in clinical status; one developed severe ventricular arrhythmias and died after 5 days of treatment; and a drug-induced hepatitis was documented in one subject at 4 weeks. No significant improvement in oxygen uptake at peak exercise and the anaerobic threshold was observed after long-term treatment (assessed at 6 and 12 weeks). Hemodynamic responsiveness to piroximone was sustained in five patients who underwent repeat evaluation at 12 weeks. Thus, long-term treatment with piroximone was not associated with an improvement in maximal and submaximal exercise capacity in patients with congestive heart failure. Serious adverse effects were observed with the administration of this drug.