enalapril and pimobendan

In view of growing scepticism as to the efficacy and safety of agents with predominant phosphodiesterase inhibiting properties in heart failure, the clinical efficacy and safety of pimobendan, a calcium-sensitizing and partially phosphodiesterase-inhibiting compound, was compared with enalapril in 242 patients with mild to moderate heart failure (NYHA classification II-III) despite diuretics and digitalis, and abnormal haemodynamics at baseline. Patients were randomly assigned to either pimobendan (average 10.3 mg.day-1, n = 119), or enalapril (average 10.7 mg.day-1, n = 123) in a double-blind fashion for 6 months. Forty-two pimobendan and 37 enalapril patients stopped the treatment, five pimobendan and six enalapril due to worsening of failure without death, whereas 13 and eight patients, respectively, died from cardiac disorders (ns). Other reasons for discontinuation and adverse events not leading to discontinuation were also comparable. Although Holter analysis at 14 days, but not at 6 months, indicated increased ventricular extrasystoles in pimobendan patients, these did not lead to serious clinical events. NYHA classification improved similarly in both groups, from 2.51 to 2.16 (pimobendan) and from 2.40 to 2.06 (enalapril). The number of patients needing a change in background therapy or hospitalization did not differ between the two groups. Haemodynamic variables at rest were improved by both compounds after 6 months. In contrast, only enalapril improved haemodynamics during exercise, and reduced the cardiothoracic ratio. The primary endpoint, exercise capacity, increased significantly during the first 3 months by 45 and 53 s, under pimobendan and enalapril, respectively, but, although unchanged thereafter, the improvement was no longer statistically significant at 6 months in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography, Ambulatory; Enalapril; Exercise Tolerance; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Pyridazines; Time Factors

Twenty-four patients (one female, 23 male) with mild to moderate heart failure were randomly and double-blindly assigned to an oral treatment with 5 mg enalapril twice daily or 5 mg pimobendan (UDCG 115) twice daily. After the first tablet intake, blood pressure and heart rate were measured for 6 h. Therapy continued over 6 months. Systolic arterial blood pressure dropped from 126 +/- 20 mmHg to 111 +/- 14 mmHg (P less than 0.05) after the first enalapril tablet and from 123 +/- 16 mmHg to 112 +/- 13 mmHg (P less than 0.05) after the first pimobendan tablet. After 6 months, no important changes in blood pressure were observed in the pimobendan group and only a minor decrease in the enalapril group. There was no significant change in heart rate either after the first dose or after long-term therapy with either medication. After 6 months, cardiac index increased from 2.73 +/- 0.75 l.min-1.m-2 to 3.38 +/- 0.69 l.min-1.m-2 (P less than 0.01) after pimobendam, but did not change after enalapril (2.95 +/- 0.75 l.min-1.m-2 to 2.96 +/- 0.89 l.min-1.m-2, NS). Pulmonary capillary wedge pressure decreased during pimobendan long-term therapy from 16 +/- 8 mmHg to 14 +/- 8 mmHg (NS) and during enalapril from 21 +/- 7 to 14 +/- 7 mmHg (P less than 0.01). Exercise capacity increased in the pimobendan group from 17.2 +/- 5.4 kJ to 23.0 +/- 9.6 kJ (P less than 0.05), and in the enalapril group from 20.4 +/- 11.9 kJ to 24.8 +/- 18.5 kJ (NS) during long-term therapy over 6 months. Plasma renin activity increased from 0.96 to 3.6 ng.ml-1.h-1 (P less than 0.05) during enalapril long-term therapy, but remained unchanged (1.38 vs. 1.32 ng.ml-1.h-1, NS) during pimobendan. The new inotrope, pimobendan, exerted favourable long-term effects without haemodynamic or humoral signs of tolerance development.

Topics: Aged; Body Weight; Creatinine; Double-Blind Method; Enalapril; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Potassium; Pyridazines; Renin

Pimobendan, diuretics, and an angiotensin-converting enzyme inhibitor (ACEi) are widely used for the management of chronic valvular heart disease in dogs; however, the effects of that combination on heart rate variability (HRV) are unknown. The purpose of this study was to assess the HRV of symptomatic myxomatous mitral valve degeneration (MMVD) dogs in response to therapy with a combination of pimobendan, diuretics, and ACEi.. MMVD stage C (n = 17) dogs were enrolled and a 1-hour Holter recording together with echocardiography, blood pressure measurement, and blood chemistry profiles were obtained before and 1, 3, and 6 months after oral treatment with pimobendan (0.25 mg/kg), enalapril (0.5 mg/kg), and furosemide (2 mg/kg) twice daily. The results revealed that MMVD stage C dogs at the baseline had lower values of time-domain indices, low frequency (LF), high frequency (HF), and total power, as well as higher value of LF/HF. Triple therapy significantly increases these parameters in MMVD stage C dogs (P < 0.05). A positive moderate correlation was observed between time domain parameters and a left ventricular internal diastole diameter normalized to body weight (P < 0.05).. It can be concluded that MMVD stage C dogs possess low HRV due to either the withdrawal of parasympathetic tone or enhanced sympathetic activation, and a combination therapy was shown to enhance cardiac autonomic modulation inferred from the increased heart rate variability. Therefore, a combination therapy may be useful for restoring normal autonomic nervous system activity in dogs with MMVD stage C.

Topics: Animals; Cardiotonic Agents; Diuretics; Dog Diseases; Dogs; Enalapril; Furosemide; Heart Rate; Mitral Valve; Mitral Valve Prolapse

Abstract: An aquarium-housed, 6-mo-old African penguin (Spheniscus demersus) presented with acute respiratory distress. Auscultation revealed a grade II-III systolic murmur in the absence of adventitial sounds, and an enlarged heart without pulmonary edema was seen radiographically. Echocardiographic evaluation revealed atrioventricular (AV) valvular dysplasia and ventricular enlargement. The penguin was treated with enalapril, furosemide, and pimobendan but died within 3 wk of detection of the murmur. Congenital dysplasia of the right AV valve with right atrial and ventricular dilation and ventricular hypertrophy were diagnosed on postmortem examination.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Animals, Zoo; Bird Diseases; Cardiotonic Agents; Diuretics; Enalapril; Fatal Outcome; Furosemide; Heart Failure; Heart Valve Diseases; Male; Pyridazines; Spheniscidae

This retrospective study reports the survival time [onset of congestive heart failure (CHF) to death from any cause] of 21 dogs with mitral regurgitation (MR) and CHF treated with a combination of furosemide, angiotensin-converting enzyme inhibitor (ACEI, benazepril, or enalapril), pimobendan, spironolactone, and amlodipine. Baseline echocardiographic data: end-systolic and end-diastolic volume indices (ESVI and EDVI), left atrium to aorta ratio (LA/Ao), and regurgitant fraction (RF) are reported. Median survival time (MST) was 430 d. Initial dosage of furosemide (P = 0.0081) and LA/Ao (P = 0.042) were negatively associated with survival. Baseline echocardiographic indices (mean ± standard deviation) were 40.24 ± 16.76 for ESVI, 161.48 ± 44.49 mL/m(2) for EDVI, 2.11 ± 0.75 for LA/Ao, and 64.71 ± 16.85% for RF. Combining furosemide, ACEI, pimobendan, spironolactone, and amlodipine may result in long survival times in dogs with MR and CHF. Severity of MR at onset of CHF is at least moderate.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Cardiotonic Agents; Death, Sudden, Cardiac; Dog Diseases; Dogs; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Failure; Male; Mitral Valve Insufficiency; Pyridazines; Retrospective Studies; Ultrasonography

Topics: Cardiac Output, Low; Cardiotonic Agents; Enalapril; Humans; Placebos; Pyridazines; Research Design