title: Comparative hemodynamic effects of OPC-18790 and dobutamine in patients with advanced heart failure.
abstract: OPC-18790 (Otsuka America Pharmaceutical, Rockville, MD), a novel positive inotropic agent, produces titratable hemodynamic benefits in patients with advanced heart failure. In such patients, OPC-18790 has been shown to acutely increase the cardiac index, while reducing systemic vascular resistance and left ventricular filling pressure, without an associated increase in heart rate. This study was performed to compare the acute hemodynamic effects of OPC-18790 and the beta-adrenergic receptor agonist, dobutamine, in patients with advanced heart failure. OPC-18790 and dobutamine were compared on successive days in 13 patients with worsening New York Heart Association class III or IV heart failure. The mean (+/- SEM) left ventricular ejection fraction was 15 +/- 2% (range, 6-29%). Pretreatment hemodynamics were: heart rate, 96 +/- 2 beats/min; mean arterial pressure, 77 +/- 3 mmHg; cardiac index, 1.80 +/- 0.10 L/min/m2; pulmonary capillary wedge pressure, 27 +/- 1 mmHg; mean pulmonary arterial pressure, 41 +/- 2 mmHg; and systemic vascular resistance, 1,732 +/- 152 dynes.s/cm5. At infusion rates yielding comparable increases in the cardiac index (5 micrograms/kg/min for 2 hours for each drug), OPC-18790 produced significantly more favorable effects on heart rate (-2 +/- 3% vs 11 +/- 4%; P = .01), pulmonary capillary wedge pressure (-32 +/- 4% vs -17 +/- 8%; P = .04), mean pulmonary arterial pressure (-14 +/- 3% vs 6 +/- 11%; P = .06), stroke volume index (48 +/- 8% vs 29 +/- 7%; P = .02), stroke work index (70 +/- 11 vs 42% +/- 12%; P = .03), and rate pressure product (2 +/- 4% vs 14 +/- 4%; P = .05). The hemodynamic profile for OPC-18790 differs from dobutamine, with OPC-18790 exhibiting no increase in heart rate, greater preload reduction, and an increase in cardiac performance at a lower estimated metabolic cost.
authors.affiliation: Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: W T
authors.initials: WT
authors.lastname: Abraham
authors.forename: B D
authors.initials: BD
authors.lastname: Lowes
authors.forename: M
authors.initials: M
authors.lastname: White
authors.forename: D A
authors.initials: DA
authors.lastname: Ferguson
authors.forename: C A
authors.initials: CA
authors.lastname: Scheffel
authors.forename: E E
authors.initials: EE
authors.lastname: Wolfel
authors.forename: J
authors.initials: J
authors.lastname: Lindenfeld
authors.forename: M R
authors.initials: MR
authors.lastname: Bristow
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000368:Aged; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D015363:Quinolones; C077543:toborinone; D004280:Dobutamine