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

Pimobendan, a new oral cardiotonic and vasodilator agent, increases myocardial contractile force through specific inhibition of phosphodiesterase type III 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.     

Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study

A number of studies have shown short-term hemodynamic and symptomatic improvement in patients with congestive heart failure treated with angiotensin converting-enzyme inhibitors. The long-term efficacy of the oral long-acting converting-enzyme inhibitor enalapril remains to be established in controlled studies. We evaluated this drug in 36 patients with New York Heart Association functional class II to III heart failure who were clinically stable on digoxin and diuretic therapy. After baseline assessment of symptoms, exercise capacity, and results of echocardiographic examination and right heart catheterization, patients were randomly assigned to treatment with 5 mg enalapril twice daily (n = 18) or placebo (n = 18) in a double-blind fashion. The two groups had similar clinical, echocardiographic, and hemodynamic characteristics before treatment. After 3 months of treatment, the enalapril group showed a significant improvement as judged by subjective patient impression, functional class, and exercise duration (9.3 +/- 5.7 vs 17.6 +/- 5.6 min; p less than .001). Diuretic dosage was reduced in six patients and increased in one patient, one patient had died and another had been withdrawn from the study. In the placebo group there was no significant change with respect to patient impression, functional class, or exercise duration; diuretic dosage was increased in seven patients and four patients had died. Echocardiographic left ventricular dimensions were significantly reduced and left ventricular shortening fraction significantly increased in the enalapril group but were unchanged in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of long-term treatment with pimobendan on neurohumoral factors in patients with non-ischemic chronic moderate heart failure.

To evaluate the effects of the addition of pimobendan to an optimal basic regimen on plasma levels of neurohumoral factors in patients with non-ischemic, moderate heart failure during 2-year follow-up. This prospective, observational study involved 16 patients with non-ischemic, moderate heart failure [New York Heart Association (NYHA) functional class IIM-III] receiving an optimal basic regimen of digitalis, diuretics and angiotensin-converting enzyme inhibitor. Eight patients (Group P) were also administered pimobendan at a dose of 2.5 or 5 mg daily, while the other 8 served as controls (Group C). After 3 months of pimobendan administration, the plasma levels of norepinephrine and atrial natriuretic peptide and brain natriuretic peptide decreased and left ventricular ejection fraction improved. After 1 year, the cardiac symptoms, assessed using the Specific Activity Scale as well as the NYHA functional class, improved and the left ventricular end-diastolic diameter decreased. These improvements in Group P were maintained for 2 years. However, in Group C, the cardiac symptoms and the neurohumoral factor levels remained unchanged or deteriorated during this study, and one patient died of heart failure. Long-term combination therapy with the optimal basic regimen and pimobendan has potentially beneficial effects on neurohumoral factor levels and cardiac symptoms in patients with non-ischemic, chronic moderate heart failure.     

Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure

Calcium sensitization increases myocardial contractility byimproving energy utlization of the myocardium, without an increasein intracellular concentrations of cyclic adenosine monophosphate.The calcium sensitizer most extensively studied up to now ispimobendan (UD-CG 115 BS). Vasodilatation results primarilyfrom phosphodiesterase III inhibition Orally administered pimobendan appears rapidly in plasma. Apeak concentration is reached 1.5 h after drug intake; eliminationfrom the plasma compartment has a half-life of 1.5 h. First-passhepatic O-desmethylation of pimobendan produces the active metaboliteUD-CG 212; plasma concentration curves of UD-CG 212 are similarto those of pimobendan, with apeak concentration 1–2 hlater than the peak concentration of the parent compound. In patients with chronic congestive heart failure, pimobendanproduces a dose-dependent and prolonged decrease in pulmonarycapillary wedge pressure and an increase in cardiac output.Maintenance doses ofpimobendan are well tolerated and may leadto lasting symptomatic improvement in patients with heart failure;open and blinded trials show that exercise tolerance increases.No attenuation of these effects is seen during long-term therapywith pimobendan. Patients in chronic congestive heart failure frequently diesuddenly; many inotropic agents increase the incidence of suddendeath in these patients. Although proarrhythmia has never beenobserved with pimobendan, arrhythmia suppression with amiodaroneseems prudent in heart failure patients receiving maintenancedoses of pimobendan.     

Acute and chronic efficacy of felodipine in congestive heart failure

In 13 patients with congestive heart failure we tested the acute hemodynamic effects of 5 vs. 10 mg felodipine tablets, in a double-blind, cross-over study. One hour after felodipine 5 mg, echocardiographic ejection fraction (%), cardiac index (thermodilution-ml/min/m2), and pulmonary wedge pressure (mm Hg) significantly changed (from 21 +/- 2 to 26 +/- 2, 2350 +/- 150 to 2790 +/- 160, 24 +/- 4 to 17 +/- 4) while they remained steady after felodipine 10 mg. The greatest stroke index increases were associated with felodipine 5 mg in 12 patients and 10 mg in 1 patient. Therefore we evaluated (open study) the long-term (2 months- 1 year) clinical and hemodynamic efficacy following the treatment with the acutely most effective dose (twice daily). After 2 months ejection fraction, cardiac index and pulmonary wedge pressure were respectively 24 +/- 2, 2550 +/- 150, and 18 +/- 4 (12 hours after the last drug administration, n = 11, P less than 0.02 from baseline). These parameters further increased one to two hours after the following administration of felodipine. Clinical improvement (reduction of 1 functional class, according to the New York Heart Association) was observed in 8/13 patients. These 8 patients participated to the one year follow-up. In 5 patients follow-up was interrupted because of acute cardiovascular events. However, before study interruption (5 patients) or ending (3 patients) clinical status did not worsen and ejection fraction remained higher than in the pretreatment period. Therefore, low dose felodipine might be used in the treatment of congestive heart failure.     

Acute and long-term effects of pimobendan (UD-CG 115) in NYHA II and III heart failure. Results of a randomized multicenter double-blind study]

The effects of pimobendan (UD-CG 115) on hemodynamics and exercise capacity after acute (single dose) and chronic (6 month) oral treatment, as well as acute treatment after 6 months were investigated in 67 patients with chronic heart failure of NYHA classes II or III, which had persisted in spite of treatment with diuretics and digitalis. They were treated with pimobendan (2.5 mg bid or 5 mg) or placebo in a randomized, double-blind multicenter trial. With a single administration before and after 6 months' treatment there was-compared to placebo-a significant fall in pulmonary capillary pressure (PCP) at rest (R) and during exercise (E) of 7% to 24%. Right atrial pressure (R) and pulmonary arterial pressure (PAP) (R, E) decreased after pimobendan on day 1; cardiac index (E) increased significantly. All other parameters were not influenced. After chronic therapy, PCP (E), PAP (E), LV stroke work index (E), and pulmonary resistance (R and E) values were significantly lowered by pimobendan when compared to day 1. Exercise duration was prolonged after 6 months by 83 s and 47 s after 5 and 10 mg/day, resp., compared to the placebo group (group difference not significant). Subjective wellbeing was improved in all three groups (no group difference). Clinical symptoms were not altered; six patients (two in each group) died suddenly. Another nine patients discontinued the trial prematurely because of poor efficacy or adverse events (no group difference). Overall, pimobendan was well-tolerated and had favorable effects on both acute and chronic hemodynamics and on exercise capacity. There was no evidence of any tolerance development.     

Reduction in left ventricular volume and improvement in hemodynamics following intravenous administration of pimobendan (UDGG 115 BS) in dilated cardiomyopathy

Acute cardiovascular effects of 5 mg (group I, n = 6) and 10 mg (group II, n = 6) i.v. pimobendan (UDCG 115 BS) were studied by right and left heart catheterizations in patients suffering from idiopathic dilated cardiomyopathy (NYHA II and III). Before and 2.5 h after application of pimobendan left ventricular volumes and left ventricular dP/dtmax were evaluated by left heart catheterization. Right atrial pressure (RAP), pulmonary capillary wedge pressure (PCP), cardiac output (CO), heart rate, and systemic blood pressure were assessed before and 2.5, 4, and 6 h after administration of pimobendan. PCP was reduced from 12.2 +/- 7.5 to 8.3 +/- 7.1 mm Hg (p less than 0.05) by 5 mg of pimobendan, and from 18.3 +/- 6.2 to 6.2 +/- 3.4 mm Hg (p less than 0.005) by 10 mg of pimobendan. Reduction of RAP was significant only in group II (from 6.2 +/- 3.2 to 1.2 +/- 0.9 mm Hg; p less than 0.05). In contrast to other hemodynamic parameters, the significant increase of CO exhibited no dose-dependency. Only 10 mg of pimobendan induced a temporary reduction of mean arterial blood pressure. An increase in heart rate occurred only in group I and was merely transient. Left ventricular end diastolic and end systolic volume indices were clearly reduced by 5 mg as well as by 10 mg of pimobendan. A significant rise of left ventricular ejection fraction occurred only in group II. However, left ventricular dP/dtmax was increased significantly in both groups. No adverse effects were noted during acute administration of pimobendan. Therefore, intravenous pimobendan may be a useful drug in the treatment of acute cardiac failure.     

Effects of acute and chronic ibopamine administration on resting and exercise hemodynamics, plasma catecholamines and functional capacity of patients with chronic congestive heart failure.

The effects of acute and chronic ibopamine treatment on resting and exercise hemodynamics, exercise capacity and plasma catecholamines were evaluated in 25 patients with chronic heart failure, using a double-blind, parallel, placebo-controlled design. During 2 months of therapy with either placebo or ibopamine (100 mg, 3 times daily), 1 patient was withdrawn from each group for worsening heart failure, New York Heart Association functional class improved in 4 patients on ibopamine and in 1 on placebo, and furosemide dose could be decreased in 4 on ibopamine and in no patient on placebo. Acute ibopamine administration induced, in comparison with placebo, a significant increase of cardiac and stroke volume indexes both at rest and peak exercise, with a reduction of systemic vascular resistance. These hemodynamic changes were maintained also after chronic therapy, with no evidence of tolerance development. Exercise capacity (evaluated as peak exercise duration and oxygen consumption, and ventilatory threshold) did not significantly change. Resting and peak exercise norepinephrine plasma levels were significantly reduced after both acute and chronic ibopamine administration. Thus, the hemodynamic and neurohumoral effects of ibopamine make this drug potentially useful for the chronic treatment of congestive heart failure.     

Cardiocirculatory effects of afterload reduction with oral trimazosin in severe chronic congestive heart failure.

Because improved long-term oral vasodilator therapy for chronic congestive heart failure is needed, the cardiocirculatory effects of the new antihypertensive quinazoline derivative, trimazosin, were evaluated with use of concomitant cardiac catheterization and forearm plethysmography in nine patients with severe chronic congestive heart failure due to coronary disease. After ingestion of 100 to 300 mg (average 172 mg) of trimazosin, the greatly elevated left ventricular filling pressure decreased from 30 to 23 mm Hg and the lowered cardiac index rose from 2.02 to 2.59 liters/min per m2. Considerable improvement in cardiac function occurred within 1 hour after ingestion of trimazosin; peak efficacy was achieved after 2 hours and persisted in the 3rd hour. Heart rate was unchanged and systemic blood pressure was mildly reduced. Because pump performance was enhanced while indexes of myocardial oxygen consumption declined, ventricular efficiency increased. Vascular relaxation was produced in both the systemic resistance and capacitance beds, with venodilation slightly more prominent. This clinical investigation of the acute hemodynamic effects of trimazosin objectively demonstrates that the drug provides considerable hemodynamic benefit in cardiac dysfunction and is therefore a potentially salutary agent for treatment of patients with chronic severe congestive heart failure.     

Hemodynamic effects of pimobendan given orally in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Pimobendan (UD-CG 115 BS) was administered orally to 23 patients with congestive heart failure (functional class IV) caused by coronary artery disease (11 patients) or idiopathic dilated cardiomyopathy (12). All patients received maintenance doses of digoxin, furosemide and warfarin. Baseline data, collected during 15 hours, stayed within a 10% range. A 10-mg oral dose of pimobendan increased the heart rate from 95 +/- 20 to 109 +/- 24 beats/min (p less than 0.003). The pulmonary artery wedge pressure decreased from 23.0 +/- 5.9 to 10.1 +/- 5.2 mm Hg (p less than 0.0001), the cardiac index increased from 1.9 +/- 0.4 to 3.3 +/- 0.7 liters/min/m2 (p less than 0.0001) and the left ventricular stroke work index increased from 2,005 +/- 927 to 3,065 +/- 1,161 ml/mm Hg/m2 (p less than 0.0001). Statistically significant improvements in hemodynamic variables were still present 10 hours after the administration of pimobendan. Most patients felt better and reported no angina or other side effect, the incidence of ventricular arrhythmias was unchanged and no electrocardiographic changes suggesting ischemia were observed. Patients with severe congestive heart failure experienced a prolonged improvement of their cardiovascular condition after a single dose of pimobendan.     

A placebo-controlled,randomized, double-blind study of OPC-8212 in patients with mild chronic heart failure

Summary OPC-8212 is a newly synthesized, orally effective inotropic agent. Previous studies have shown short-term hemodynamic and symptomatic improvement in patients with congestive heart failure. However, the long-term efficacy of this agent remains to be established. Eighty-three patients with chronic heart failure were randomly assigned to treatment with either OPC-8212 (n=45) or matching placebo (n-38).Of the placebo-treated patients, two patients died and another six patients were withdrawn from the study because of a deterioration of heart failure, while only 1 out of 45 OPC-8212-treated patients were withdrawn because of increased congestive symptoms.After 12 weeks of treatment, the OPC-8212 group showed a significant improvement in their numerical scores in sense of well-being as judged by the patients' subscale A (p<0.01) and their physician's general impression of the patients' status (p<0.01). The ejection fraction obtained from echocardiography increased from a mean (±SEM) baseline value of 42.8±2.6% to 46.6±2.9% (p<0.05) in the OPC-8212 group and 44.4±3.7% to 45.5±4.1% in the placebo group. These effects were not associated with an increase in the heart rate. The treatment was well tolerated without any limiting side effects.Thus, OPC-8212 is effective in patients with chronic heart failure, providing significant hemodynamic and symptomatic benefit in chronic treatment, together with a possible improvement of the prognosis of patients with heart failure.     

Long-term control of congestive heart failure with captopril

The long-term effects of captopril therapy were assessed by sequential hemodynamic studies over a 6 month period in 19 patients with resistant congestive heart failure. Initial improvement during the first week of therapy was noted only in 11 and was marked by significant (p < 0.005) increases in cardiac output and stroke volume, slowing of heart rate, and reduction of total peripheral resistance. Of the remaining eight patients, seven improved subsequently with maintained therapy so that by the end of 3 months of treatment only one patient failed to respond significantly.The hemodynamic index that reflected response most consistently was the shortening in pulmonary mean transit time. Simultaneously with clinical improvement there was a reduction in cardiopulmonary volume that reflected a reduction in pulmonary congestion and probably systemic venodilation. Associated with these hemodynamic changes there was an increase in plasma renin activity and a significant reduction in plasma aldosterone, but these changes did not differ significantly between patients who responded markedly and those who responded moderately to converting enzyme inhibition.These results suggest that the response of congestive heart failure to captopril can occur gradually. Improvement was related to peripheral hemodynamic changes which led to a reduction in both total peripheral resistance and cardiopulmonary volume. The reduction in the plasma aldosterone/renin activity ratio was an effective marker of compliance.     

Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial.

PRIMARY OBJECTIVE: To determine the effects of pimobendan 2.5 and 5 mg daily on exercise capacity in patients with chronic heart failure. DESIGN: A randomised, double blind, placebo controlled trial of the addition of pimobendan to conventional treatment with a minimum follow up of 24 weeks. SETTING: Outpatient cardiology clinics in six European countries. PATIENTS: 317 patients with stable symptomatic heart failure, objectively impaired exercise capacity, and an ejection fraction of 45% or lower who were treated with at least an angiotensin converting enzyme inhibitor and a diuretic and who tolerated a test dose of pimobendan. RESULTS: Compared with placebo, both pimobendan 2.5 and 5 mg daily improved exercise duration (bicycle ergometry) by 6% (P = 0.03 and 0.05) after 24 weeks of treatment. At that time 63% of patients allocated to pimobendan and 59% of those allocated to placebo were alive and able to exercise to at least the same level as at entry (P = 0.5). No significant effects on oxygen consumption (assessed in a subgroup of patients) and on quality of life (assessed by questionnaire) were observed. Pimobendan was well tolerated. Proarrhythmic effects (24-hour electrocardiography) were not observed. In both pimobendan groups combined the hazard of death was 1.8 (95% confidence interval 0.9 to 3.5) times higher than in the placebo group. CONCLUSIONS: Pimobendan improves exercise capacity in patients with chronic heart failure who are also on conventional treatment. The balance between benefit and risk of treatment with this compound remains to be established however.     

Clinical and hemodynamic efficacy of enalapril in severe congestive heart failure

OBJECTIVES: Evaluate the clinical and hemodynamic efficacy of enalapril in the treatment of severe congestive heart failure, refractory to the classic therapeutics with diuretics and digitalis. SETTING: Hospitalized patients (pts) of a cardiac department. MATERIAL AND METHODS: 10 pts with a mean age of 57.8 years in whom a Swan-Ganz catheter was placed for 72 hours to monitor the right pressures and cardiac output, with regular control of arterial blood pressure and cardiac frequency. Low doses of enalapril (2.5 mg) were utilized at the start of the treatment and this dose was readjusted depending on the clinic and hemodynamic parameters. RESULTS: the 10 pts had the following characteristics: Basal-mean pulmonary arterial pressure (PAP) 34.1 mmHg, Pulmonary wedge pressure (PWP) 21.1 mmHg, cardiac output (CO) 4.8 l/min, cardiac index (CI) 2.8 l/min/m2. After 72 hours with enalapril treatment, these measurements were: PAP-23.8 mmHg, PWP-12.6 mmHg, CO-5.2 l/min and Cl-3.0 ll/min/m2. These differences were statistically significant. With a follow-up of 18.4 months, there was also a clinical improvement; of the 4 pts in class III, 2 moved to class II and 2 to class I; the 4 pts in class IV 4 moved to class II; two pts had died. CONCLUSIONS: In severe heart failure, the addition of enalapril to the classic therapy has allowed the immediate improvement of the clinical and hemodynamic indexes and this improvement was maintained in the follow-up period.     

Hemodynamic comparison of intravenous amrinone and dobutamine in patients with chronic congestive heart failure

Amrinone, a new inotropic agent, has been shown to be beneficial in patients with congestive heart failure. However, its hemodynamic effects have not been compared with those of currently useful catecholamines. In this study, the effects of intravenously administered dobutamine and amrinone were compared in eight patients with severe chronic congestive heart failure. Dobutamine was infused until a maximal increase in cardiac index was reached or undesirable effects were produced. This dose was then continued for 8 hours. After a return of hemodynamic values to baseline level, amrinone was infused at a rate of 40 μg/kg per min for 1 hour and then 10 μg/kg per min for 24 hours. Both drugs significantly improved cardiac index while simultaneously decreasing systemic vascular resistance and right atrial and pulmonary wedge pressures (p <0.05). Initially no differences could be found between the drugs. However, with prolonged infusion amrinone produced a sustained improvement whereas dobutamine had a decreased effectiveness. Thus, amrinone is comparable in effect with the optimal dose of dobutamine and would appear to be an extremely promising drug in the acute treatment of severe congestive heart failure.     

A dose-finding study of the hemodynamic effect of isosorbide dinitrate spray in congestive heart failure

A dose-finding study of the hemodynamic effect of a new formulation of isosorbide dinitrate (ISDN) spray was performed in 12 patients with chronic congestive heart failure. Doses of 1.25, 2.5, 5.0 mg and placebo, as 1 squirt, were randomly given to all patients. Hemodynamic measurements were performed by a Swan-Ganz catheter before and at 30 seconds and 1, 5, 10, 20 and 30 minutes after drug administration and every 30 minutes thereafter, until return of hemodynamic variables to baseline. Hemodynamic improvement evident as decreases in right-sided pressures and an increase in cardiac output was observed within 1 minute from administration of ISDN spray, and peaked at 5 minutes. Near maximal effect was achieved by the 2.5-mg dose. Thus, 2.5 mg of ISDN spray (new formulation) dose. Thus, 2.5 mg of ISDN spray (new formulation) produces rapid, near-maximal hemodynamic improvement in patients with congestive heart failure.     

The acute hemodynamic response to pirbuterol at rest and exercise in patients with heart failure with observations on long-term response

Rest and exercise hemodynamics with the beta agonist pirbuterol and a placebo preparation were studied in seven patients with severe chronic congestive heart failure. At rest, pirbuterol increased cardiac index (1.8 +/- 0.3 to 2.3 +/- 0.4 L/min/M2, p less than 0.01) and decreased systemic vascular resistance (1899 +/- 405 to 1419 +/- 257 dynes-sec-cm-5, p less than 0.01) without a significant change in heart rate, right atrial, pulmonary arterial, pulmonary arterial wedge, or systemic arterial pressures. Although there were slight increases in cardiac index at peak exercise with pirbuterol, neither total exercise time nor peak oxygen consumption were improved with this agent. No significant hemodynamic changes occurred with placebo at rest, nor was there improvement in exercise performance following placebo. Of three patients studied at six weeks, two showed total loss of hemodynamic effect of pirbuterol compared to the acute response. In conclusion, although acute rest hemodynamics improve with pirbuterol, the lack of improved acute exercise performance and the decrease in hemodynamic responsivity at six weeks appear to limit its usefulness in the treatment of heart failure.     

Hydralazine therapy in chronic congestive heart failure. Sustained central and regional hemodynamic responses

Central and regional hemodynamic parameters were evaluated at baseline and following three months of placebo or hydralazine therapy (100 mg orally every eight hours) in 20 patients with idiopathic dilated cardiomyopathy. Both control (placebo) and hydralazine groups were comparable with respect to functional classification (New York Heart Association classes III and IV) and baseline hemodynamic variables. In the hydralazine group, cardiac index increased 25 percent (2.4 +/- 0.4 to 3.0 +/- 0.5 liters/minute/m2), renal blood flow increased 26 percent (648 +/- 199 to 815 +/- 229 ml/minute), and limb blood flow was augmented by 35 percent (6.8 +/- 3.0 to 9.2 +/- 4.6 ml/dl/minute) with long-term therapy. These changes were significant (all p less than 0.05) when compared with both baseline values and values in the control group. Both central and regional hemodynamic parameters remained unaltered in the control group. Long-term hydralazine therapy (three months) elicited a favorable circulatory response in this group of patients with chronic congestive heart failure. Central or regional hemodynamic tolerance to oral hydralazine failed to develop in the majority of patients.     

曲美他嗪治疗冠心病心力衰竭的临床观察

目的:观察曲美他嗪治疗冠心病伴慢性心功能不全的临床疗效。方法:152例冠心病合并慢性心功能不全的患者,随机被分为对照组(常规治疗)和曲美他嗪组(常规治疗加曲美他嗪20mg,1次/d),各76例,观察3个月。结果:曲美他嗪组的心衰缓解情况、超声心动图的心功能指标均显著优于对照组(P<0.05)。结论:常规药物联合曲美他嗪治疗冠心病伴慢性心功能不全是一种疗效确切,安全简便的方法,值得临床推广使用。     

Clinical effects of long-term administration of pimobendan in patients with moderate congestive heart failure

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.