A multicenter, randomized, double-blind, placebo-controlled trial of pimobendan, a new cardiotonic and vasodilator agent, in patients with severe congestive heart failure

Stuart D. Katz, Spencer H. Kubo, Mariell Jessup, Suzanne Brozena, Janice M. Troha, Janice Wahl, Jay N Cohn, Edmund H. Sonnenblick, Thierry H. LeJemtel

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Pimobendan, a new oral cardiotonic and vasodilator agent, increases myocardial contractile force through specific inhibition of phosphodiesterase type Ill and increased calcium sensitivity of the myocardial contractile elements. The effects of pimobendan on left ventricular performance and maximal exercise capacity were studied in a multicenter, randomized, double-blind, placebo-controlled trial involving 52 patients with severe congestive heart failure despite diuretics, digoxin, and angiotensin-converting enzyme inhibitors. The acute hemodynamic evaluation included three single doses of 2.5, 5.0, and 10.0 mg of oral pimobendan, which was subsequently administered at a daily dose of 5 or 10 mg for 4 weeks. Acute administration of pimobendan significantly increased the resting cardiac index and lowered pulmonary capillary wedge pressure in a dose-dependent manner, whereas heart rate and systemic arterial pressure were not substantially altered. Patients receiving pimobendan, 5 and 10 mg daily, had a significantly greater increase in maximal exercise duration than those receiving placebo, that is, 144 ± 30 and 124 ± 33 seconds versus 58 ± 25 seconds (p = 0.05). Peak oxygen uptake increased by 1.7 ± 0.8 and 2.2 ± 1.3 ml/kg/min in patients receiving pimobendan at a daily dose of 5 and 10 mg, respectively, whereas it decreased by 0.1 ± 0.6 ml/kg/min in patients receiving placebo (p = 0.06). Thus pimobendan acutely improves resting left ventricular performance and chronically increases exercise duration and peak oxygen uptake in patients with severe congestive heart failure concomitantly treated with digoxin, diuretics, and angiotensin-converting enzyme inhibitors.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalAmerican Heart Journal
Volume123
Issue number1
DOIs
StatePublished - Jan 1 1992

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Cardiotonic Agents
Vasodilator Agents
Heart Failure
Placebos
Digoxin
Exercise
Angiotensin-Converting Enzyme Inhibitors
Diuretics
Oxygen
Pulmonary Wedge Pressure
Phosphoric Diester Hydrolases
pimobendan
Arterial Pressure
Heart Rate
Hemodynamics
Calcium

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A multicenter, randomized, double-blind, placebo-controlled trial of pimobendan, a new cardiotonic and vasodilator agent, in patients with severe congestive heart failure. / Katz, Stuart D.; Kubo, Spencer H.; Jessup, Mariell; Brozena, Suzanne; Troha, Janice M.; Wahl, Janice; Cohn, Jay N; Sonnenblick, Edmund H.; LeJemtel, Thierry H.

In: American Heart Journal, Vol. 123, No. 1, 01.01.1992, p. 95-103.

Research output: Contribution to journalArticle

Katz, Stuart D. ; Kubo, Spencer H. ; Jessup, Mariell ; Brozena, Suzanne ; Troha, Janice M. ; Wahl, Janice ; Cohn, Jay N ; Sonnenblick, Edmund H. ; LeJemtel, Thierry H. / A multicenter, randomized, double-blind, placebo-controlled trial of pimobendan, a new cardiotonic and vasodilator agent, in patients with severe congestive heart failure. In: American Heart Journal. 1992 ; Vol. 123, No. 1. pp. 95-103.
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abstract = "Pimobendan, a new oral cardiotonic and vasodilator agent, increases myocardial contractile force through specific inhibition of phosphodiesterase type Ill and increased calcium sensitivity of the myocardial contractile elements. The effects of pimobendan on left ventricular performance and maximal exercise capacity were studied in a multicenter, randomized, double-blind, placebo-controlled trial involving 52 patients with severe congestive heart failure despite diuretics, digoxin, and angiotensin-converting enzyme inhibitors. The acute hemodynamic evaluation included three single doses of 2.5, 5.0, and 10.0 mg of oral pimobendan, which was subsequently administered at a daily dose of 5 or 10 mg for 4 weeks. Acute administration of pimobendan significantly increased the resting cardiac index and lowered pulmonary capillary wedge pressure in a dose-dependent manner, whereas heart rate and systemic arterial pressure were not substantially altered. Patients receiving pimobendan, 5 and 10 mg daily, had a significantly greater increase in maximal exercise duration than those receiving placebo, that is, 144 ± 30 and 124 ± 33 seconds versus 58 ± 25 seconds (p = 0.05). Peak oxygen uptake increased by 1.7 ± 0.8 and 2.2 ± 1.3 ml/kg/min in patients receiving pimobendan at a daily dose of 5 and 10 mg, respectively, whereas it decreased by 0.1 ± 0.6 ml/kg/min in patients receiving placebo (p = 0.06). Thus pimobendan acutely improves resting left ventricular performance and chronically increases exercise duration and peak oxygen uptake in patients with severe congestive heart failure concomitantly treated with digoxin, diuretics, and angiotensin-converting enzyme inhibitors.",
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