Persistent hemodynamic effects without long-term clinical benefits in response to oral piroximone (MDL 19,205) in patients with congestive heart failure.

Piroximone (MDL 19,205), a new phosphodiesterase inhibitor with positive inotropic and vasodilating properties, was administered orally to 12 patients with severe congestive heart failure (NYHA class III to IV). After a mean dose of 1.7 +/- 0.4 (SD) mg/kg, cardiac index increased from 2.0 +/- 0.5 to 3.0 +/- 0.6 liters/min/m2 while pulmonary wedge pressure decreased from 23 +/- 6 to 15.6 +/- 7 mm Hg and systemic vascular resistance from 1520 +/- 370 to 1000 +/- 320 dyne-sec-cm-5. Mean arterial pressure was slightly reduced from 80 +/- 13 to 75 +/- 11 mm Hg and forearm blood flow increased by 79% (all p less than .01). Eleven patients were selected for long-term treatment. Two patients received a heart transplant soon after the treatment was started. The remaining nine patients were followed for a mean of 5.6 months (range 2 to 10). Severe congestive heart failure recurred in eight of these nine patients, resulting in the death of three patients within 4 months. The remaining six patients underwent repeat hemodynamic evaluation 2 months after the initiation of the treatment. A short-term hemodynamic response to the drug in this group demonstrated that piroximone retains its circulatory effect during continuous therapy. Nevertheless, three more patients of this group died within 8 months and two required heart transplants. Of the nine patients receiving long-term treatment, only one had sustained subjective improvement and increased exercise capacity. Therefore long-term therapy with piroximone did not appear to benefit patients with severe congestive heart failure. A drug-related deterioration of their clinical status cannot be excluded.