Summary
The long-term efficacy of the positive inotropic and vasodilator drug, pimobendan, was assessed in 21 patients suffering from symptomatic heart failure. Patients were randomized to 16 weeks of double-blind therapy with either 2.5 or 5.0mg/day of pimobendan (n = 10), or a matching placebo (n = 11). Patients were blinded on the study drug if their clinical status had not substantially worsened during the study. Of the placebo-treated patients, 5 patients were withdrawn from the study because of a deterioration of their heart failure, while none of the active treated group was withdrawn because of increased symptoms. Quality of life, assessed by the specific activity scale derived from the metabolic costs of individual physical activity, was 3.45 ± 0.90 (SD) mets in the baseline state and increased significantly after week 16, averaging 5.07 ± 1.40 and 4.67 ± 1.47 mets at weeks 16 and 24, respectively. In the placebo-treated group, the specific activity scale was 3.27 ± 1.21 mets at the baseline and remained unchanged throughout the study period. Patients treated with pimobendan were able to significantly increase their exercise duration. The accompanying increase in peak oxygen uptake was statistically insignificant, due to the limited number of patients enrolled in the study. These results suggest that in contrast to the recent pessimistic view of the long-term efficacy of cardiotonic drugs, pimobendan is beneficial in treating patients with congestive heart failure and may favorably modify their prognosis. Further largescale evaluation of this agent is warranted.
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References
Cohn JN (1988) Current therapy of the failing heart. Circulation 78:1099–1107
The SOLVD Investigators (1991) Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 325:293–302
Cohn JN, Johnson G, Ziesche S, et al. (1991) A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 325:303–310
Cody RJ, Packer M, Colucci WS (1988) Do positive inotropic agents adversely affect the survival of patients with chronic congestive heart failure? J Am Coll Cardiol 12:559–569
Packer M, Carver JR, Rodeheffer RJ, et al. (1991) Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 325:1468–1475
Ruegg JC (1986) Effects of new inotropic agents on Ca++ sensitivity of contractile proteins. Circulation 73 [Suppl III]:78–83
Ruegg JC, Morano I (1989) Calcium-sensitivity modulation of cardiac myofibrillar proteins. J Cardiovasc Pharmacol 14 [Suppl III]:S20-S23
Fujino K, Sperelakis N, Solaro RJ (1988) Sensitization of dog and guinea pig heart myofilaments to Ca2+ activation and the inotropic effect of pimobendan: comparison with milrinone. Circ Res 63:911–922
Berger C, Meyer W, Scholz H, et al. (1985) Effect of the benzimidazole derivatives pimobendan and 2-(4-hydroxy-phenyl)-5-(5-methyl-3-oxo-4. 5-dihydro-2H-6-pyridazinyl) benzimidazole. HCl on phosphodiesterase activity and force of contraction in guinea-pig hearts. Arzneimittelforschung 35:1688
Scholz H, Meyer W (1986) Phosphodiesterase-inhibiting properties of newer inotropic agents. Circulation 73 [Suppl III]:99–108
Hagemeijer F, Brand HJ, Roth W (1989) Cardiovascular effects and plasma level profile of pimobendan (UD-CG 115 BS) and its metabolite UD-CG 212 in patients with congestive heart failure after single and repeated oral dosing. J Cardiovasc Pharmacol 14:302–310
Walter M, Liebens I, Goethals H, et al. (1988) Pimobendane (UD-CG 115 BS) in the treatment of severe congestive heart failure. An acute haemodynamic crossover and double-blind study with two different doses. Br J Clin Pharmacol 25:323–329
Renard M, Walter M, Liebens I, et al. (1988) Pimobendane (UD-CG 115 BS) in chronic congestive heart failure. Chest 93:1159–1164
Hauf GF, Grom E, Johnchen E, et al. (1989) Acute and long-term hemodynamic effects of pimobendan (UD-CG 115 BS) in comparison with captopril. J Cardiovasc Pharmacol 14 [Suppl II]:S49-S56
Spencer H Kubo, Steven Gollub, et al. (1992) Beneficial effects of pimobendan on exercise tolerance and quality of life in patients with heart failure: results of a multicenter trial. Circulation 85:942–949
Remme W, Krayenbuhl H, Baumann G, et al. (1992) Efficacy and safety of pimobendan in moderate CHF. A double-blind parallel 6 month comparison with enalapril (abstract). J Am Coll Cardiol 19:261A
Sasayama S, Asanoi H, Ishizaka S, et al. (1992) Evaluation of functional capacity of patients with congestive heart failure. In: Yasuda H, Morgan HE (eds) New aspect in the treatment of failing heart. Springer, Berlin Heidelberg New York Tokyo, pp 113–117
Katz AM (1988) Cellular Mechanisms in congestive heart failure. Am J Cardiol 62:3A–8A
Holubarsch C, Hasenfuss G, Just H, et al. (1989) Influence of the positive inotropic substnace pimobendan (UD-CG 115 BS) on contractile economy of guinea pig papillary muscles. J Cardiovasc Pharmacol 14 [Suppl II]:S13-S17
Hasenfuss G, Holubarsch C, Heiss HW, et al. (1989) Influence of the calcium-sensitizer UDCG-115 on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy. Comparison with nitroprusside. Basic Res Cardiol 84 [Suppl I]:225–233
Goldman L, Hashimoto B, Cook EF (1981) Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new Specific Activity Scale. Circulation 64:1227–1234
OPC-8212 Multicenter Research Group (1990) A placebo-controlled, randomized, double-blind study of OPC-8212 in patients with mild chronic heart failure. Cardiovasc Drugs Ther 4:419–426
Feldman AM, Baughman KL, Lee WK, et al. (1991) Usefulness of OPC-8212, a quinolinone derivative, for chronic congestive heart failure in patients with ischemic heart disease or idiopathic dilated cardiomyopathy. Am J Cardiol 68:1203–1210
Feldman AM for the vesnarinon study group (1993) Effects of vesnarinon on morbidity and mortality in patients with heart failure. N Engl J Med 329:149–155
Phillips PJ, Gwathmey JK, Feldman MD, et al. (1990) Post-extrasystolic potentiation and the force-frequency relationship: differential augmentation of myocardial contractility in working myocardium from patients with end-stage heart failure. J Mol Cell Cardiol 22:99–110
Feldman MD, Gwathmey JK, Phillips P, et al. (1988) Reversal of the force-frequency relationship in working myocardium from patients with end-stage heart failure. J Applied Cardiol 3:273–283
Hagemeijer F (1991) Intractable heart failure despite angiotensin-converting enzyme inhibitors, digoxin, and diuretics: long-term effectiveness of add-on therapy with pimobendan. Am Heart J 122:517–522
van Meel JCA, Mauz ABM, Wienen W, et al. (1989) Pimobendan increases survival of cardiomyopathic hamsters. J Cardiovasc Pharmacol 13:508–509
Verdouw PD, Hartog JM, Duncker DJ, et al. (1986) Cardiovascular profile of pimobendan, a benzimidazolepyridazinone derivative with vasodilating and inotropic properties. Eur J Pharmacol 126:21–30
Arnout J, Deckmyn H, Huybrechts E, et al. (1986) UDCG 115 and 212, two benzimidazo-pyridazinones with broad spectrum antiplatelet activity. Thromb Haemost 54:134
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Sasayama, S., Asanoi, H., Kihara, Y. et al. Clinical effects of long-term administration of pimobendan in patients with moderate congestive heart failure. Heart Vessels 9, 113–120 (1994). https://doi.org/10.1007/BF01745236
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DOI: https://doi.org/10.1007/BF01745236