Piroximone (MDL 19,205) in the treatment of unstable and stable chronic cardiac failure.

The hemodynamic and clinical response to oral and intravenous piroximone was examined in 25 patients with chronic cardiac failure secondary to ischemic or myopathic heart disease: 14 with severe failure, who were clinically unstable (group I), and 11 with stable failure of mild to moderate severity (group II) in whom maximal O2 uptake (VO2 max) to treadmill exercise could be monitored serially. Intravenous (0.5 to 1.0 mg/kg) and oral (0.7 to 4.9 mg/kg) piroximone significantly (p less than 0.05) improved right and left ventricular pump function in both groups while causing an insignificant rise in heart rate and reduction in arterial pressure. Myocardial O2 uptake was not altered acutely or subacutely after piroximone, and myocardial lactate production was not observed. The salutary hemodynamic response to oral piroximone was sustained for 5 hours and there was no evidence of tolerance to the third and fourth doses. In group II, VO2 max was increased (p less than 0.05) at 4, 8, 12, 24, and 48 weeks of oral piroximone therapy. Adverse gastrointestinal effects were observed in two patients and a supraventricular tachycardia in another. Thus, piroximone may prove useful in the long-term management of chronic cardiac failure. Controlled clinical trials should be undertaken to determine the ultimate efficacy and safety of piroximone in these patients.