OPC-8212 in the treatment of congestive heart failure: Results of a pilot study

To characterize the effects of OPC-8212, a quinolone inotropic agent, in patients with heart failure, we utilized invesive homodynamics, exercise testing, 24-hour ambulatory electrocardiograms, and two patient self-assessment questionnaires, before and after 1 month of treatment with OPC-8212, in 17 patients with moderate to severe congestive heart failure. There were no significant changes from baseline in heart rate (83±8 beats/min), mean arterial pressure (70±15 mmHg), pulmonary wedge pressure (18±7 mmHg), or cardiac index (2.3±0.4 L/min/m²) following treatment with OPC-8212. Both exercise duration (5.3±1.6 min) and peak oxygen consumption (12.0±2.9 mL/kg/min) were unchanged by OPC-8212. Two independent patient self-assessment scores, the Sickness Impact Profile and the Minnesota Living with Heart Failure Questionnaire, showed improvements from 6.8 to 5.4 and 49 to 38, respectively (both p<.05), suggesting that the patients reported an improvement in daily functioning. The median ventricular premature contraction count and frequency were reduced from 1,118 beats to 243 beats (p<0.05) and 11/1,000 beats to 2,4/1,000 beats (0.05<p<0.10), respectively. Two patients developed agranulocytosis during longer-term treatment following this 1-month study. These data demonstrate that OPC-8212 did not have significant effects on hemodynamics or exercise tolerance. However, the improvement in patient self-assessment scores and the trend for improvement in ventricular arrhythmia profiles suggest that OPC-8212 may have some benefit for patients with congestive heart failure, but additional placebo-controlled, double-blind studies are necessary.