delapril and Heart-Failure

The addition of an angiotensin-converting enzyme (ACE) inhibitor to digitalis and diuretics in chronic congestive heart failure (CHF) prolongs survival and improves the clinical condition of patients. These actions depend on the inhibition of ACE and are, therefore, common to all ACE inhibitors. Thus, the inclusion of an ACE inhibitor in the therapeutic regimen of chronic CHF is mandatory, whenever feasible. The use of ACE inhibitors in chronic CHF should avoid symptomatic hypotension and inordinate decreases in renal function. To this end, ACE inhibitor therapy should progress by gradually increasing doses, and sodium intake and dosages of diuretics and ACE inhibitors should be adjusted in the light of changing circumstances. ACE inhibitors with short elimination half-lives should be preferred in chronic CHF, since they allow quicker dose adjustment than their longer-acting congeners, and given that compliance with once and twice daily dosing would be similar.

Topics: Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Heart Failure; Humans; Indans

A total of 101 patients (67 delapril, 34 placebo) with congestive heart failure, New York Heart Association (NYHA) classes II and III, entered a multicenter, randomized (2:1), double-blind, placebo-controlled study to determine the minimum effective and maximum tolerated doses of delapril. Patients received placebo or increasing doses of delapril. After a 2-week run-in period on placebo, patients were randomly assigned to delapril or placebo. The dose of delapril was 7.5 mg twice daily for 2 weeks, 15 mg twice daily for another 2 weeks, followed by 30 mg twice daily for 4 weeks. The dose was increased only if the patient did not present any symptoms of orthostatic hypotension. If such symptoms developed, the code was broken and an open treatment was continued on the minimum effective dose (delapril group). Patients with symptoms of orthostatic hypotension in the placebo group were withdrawn. At the end of the 8-week treatment, 36 (54.5%) patients in the delapril group completed the study on 30 mg twice daily, 12 (18.2%) on 15 mg twice daily, and 18 (27.3%) on 7.5 mg twice daily. Seven patients on placebo were withdrawn because of insufficient therapeutic response; one patient on delapril was lost to follow-up. There was a significant improvement (p < 0.01) in bicycle ergometric performance involving an increase in the exercise duration and the maximum workload tolerated in those patients completing the study on delapril 30 mg twice daily and those finishing on 15 mg twice daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Double-Blind Method; Exercise Test; Female; Heart Failure; Heart Rate; Humans; Indans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome

To evaluate the safety and efficacy of delapril versus enalapril in patients with congestive heart failure (CHF), New York Heart Association (NYHA) class II and III, 198 patients were enrolled in a study in 13 centers involving a double-blind parallel group design. After completing a 2-week run-in period on placebo, patients were randomized to receive delapril 7.5 mg twice daily or enalapril 2.5 mg twice daily for 2 weeks. The dose was then doubled for the remaining 6 weeks. In this phase, 1 patient in each group experienced orthostatic hypotension; the dose was then reduced to the initial dose for study completion. A total of 195 patients received active treatment (96 delapril, 99 enalapril). After 8 weeks' treatment, bicycle ergometry demonstrated a significant increase in exercise duration (p < 0.01) and workload (p < 0.01). Echo Doppler investigations showed a significant reduction (p < 0.01) in left ventricular end-systolic volume associated with a significant increase (p < 0.01) in ejection fraction and cardiac output. No clinically significant changes in blood pressure, heart rate, electrocardiogram, or biochemical and hematologic tests were found. There were no significant differences between treatment groups. Three patients in each group experienced adverse reactions requiring withdrawal of 1 patient in each group. Delapril 15 mg twice daily, like enalapril 5 mg twice daily, was effective in improving signs and symptoms of CHF and was well tolerated.

Topics: Administration, Oral; Adult; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Double-Blind Method; Echocardiography, Doppler; Enalapril; Exercise Test; Female; Heart Failure; Humans; Indans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome

In this study delapril and captopril were compared in outpatients with congestive heart failure (CHF), New York Heart Association (NYHA) classes III and IV, in a double-blind study of efficacy and safety. Efficacy was evaluated by monitoring changes in the NYHA classification, exercise work, hemodynamic parameters, Kostuk's classification, and clinical signs and symptoms. Safety was monitored by a variety of laboratory tests, including renal and hepatic function, urinalysis, routine hematology testing, and the reporting of adverse events. Analysis of the data obtained revealed that delapril and captopril exhibit equal efficacy over the dosage ranges studied. There was a greater improvement of NYHA classification in terms of CHF signs and symptoms and ergometric workload in the delapril group; however, this did not reach statistical significance. The safety of the 2 drugs was also comparable, with no significant differences in any of the parameters measured at the start and end of the study. There was no statistically significant difference in the reporting of adverse events between the 2 drugs, although the sample size studied was small. There were no significant differences between the 2 drugs in terms of their effects on arterial blood pressure and no difference between prestudy and post-treatment arterial blood pressure measurements.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Ambulatory Care; Angiotensin-Converting Enzyme Inhibitors; Captopril; Double-Blind Method; Exercise Test; Female; Heart Failure; Humans; Indans; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Treatment Outcome

In this controlled trial, 30 elderly patients with congestive heart failure, New York Heart Association (NYHA) classes II and III, were randomly assigned to treatment with captopril 25 mg three times daily or delapril 15 mg twice daily. At the end of an 8-week treatment period, clinical symptoms of heart failure were significantly relieved by both drugs, with a consistent and statistically significant improvement in patients' quality of life evaluated using a symptoms/activity scale (p < 0.001). None of the patients was judged NYHA class III at the end of the trial and 40% were assigned to class I (p < 0.01). There was a relevant, but not statistically significant, increase in exercise duration in both treatment groups (10% captopril group, 14% delapril group), but the number of patients discontinuing the exercise test for dyspnea was 50% less in the delapril group. Neither drug had evident effects on echocardiographic left ventricular parameters. Two patients treated with captopril and 3 with delapril complained of mild-to-moderate adverse reactions. The safety of both drugs was confirmed by laboratory tests.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Exercise Test; Female; Heart Failure; Humans; Indans; Male; Quality of Life; Severity of Illness Index; Treatment Outcome; Ventricular Function, Left

The results after the first 6 months of the 1-year treatment of this multicenter, randomized, open, parallel-group design study of delapril versus enalapril in patients with congestive heart failure (CHF), New York Heart Association (NYHA) classes II and III, are presented. The initial dose of delapril (7.5 mg twice daily) and enalapril (2.5 mg twice daily) could be doubled on a 2-weekly basis (from the beginning of the study) to a maximum of 30 mg twice daily and 10 mg twice daily, respectively. The evaluation of the efficacy was based on the changes of NYHA class, results of exercise testing involving bicycle ergometry (duration of exercise, workload, work performed, double product) performed before and after 3 months' treatment, echocardiography (left ventricular end-diastolic volume and end-systolic volume, ejection fraction, and left ventricular wall stress) at baseline and after 3 and 6 months of treatment and changes in cardiothoracic ratio, electrocardiography, and NYHA class, and patient's opinion of efficacy. Safety was evaluated by monitoring the adverse reactions, laboratory tests, and blood pressure. At 3 months, both treatments had produced a significant improvement compared with baseline in the duration of exercise, workload, and work performed in the bicycle ergometry test as well as in the ejection fraction and in left ventricular wall stress after 6 months of treatment. In addition, after 3 and 6 months of treatment, delapril produced a significant decrease in left ventricular end-systolic volume. Improvement of at least one NYHA class was observed in 20% of delapril patients and 14% of enalapril patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Echocardiography; Enalapril; Exercise Test; Female; Heart Failure; Humans; Indans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome

We investigated the effect of chronic administration of an angiotensin II type-1 receptor antagonist in the development of heart failure due to volume overload in rats.. Aortocaval fistula (AVF), a model of volume overloaded heart failure, was induced in rats by our newly developed technique using a simple and rapid 18-gauge needle multipuncture. After 3 weeks of oral administration of an angiotensin II receptor antagonist TCV-116, 1 mg/kg per day, we evaluated the hemodynamics, heart weight, and degree of left ventricular dilatation. We also compared the effect of TCV-116 with that of an angiotensin-converting enzyme inhibitor delapril, 1 g/L in drinking water.. AVF heart failure produced by our technique exhibited significant increases in the left ventricular end-diastolic pressure (LVEDP) (12 = 1 vs 4 +/- 1 mmHg, p < 0.05), right atrial pressure (RAP) (5.0 +/- 0.6 vs 1.0 +/- 0.4 mmHg, p < 0.05), right ventricular systolic pressure (RVSP) (58 +/- 6 vs 33 +/- 1 mmHg, p < 0.05), left ventricular weight (LVW) (3.00 +/- 0.13 vs 2.09 +/- 0.04 g/kg BW, p < 0.05), right ventricular weight (RVW) (0.93 +/- 0.05 vs 0.59 +/- 0.01 g/kg BW, p < 0.05), and left ventricular end-diastolic volume index (LVEDVI) (2.55 +/- 0.14 vs 0.80 +/- 0.12 ml/kg BW, p < 0.05) as compared with these values in sham-operated rats. There were no differences in shunt ratio between untreated and TCV-116- and delapril-treated AVF groups. TCV-116 improved these hemodynamics, as did delapril (TCV-116 vs delapril: LVEDP 8 +/- 1 vs 8 +/- 1, RAP: 3.8 +/- 0.6 vs 2.3 +/- 1.4, RASP: 50 +/- 2 vs 46 +/- 3, LVW: 2.53 +/- 0.11 vs 2.52 +/- 0.15, RVW: 0.80 +/- 0.04 vs 0.77 +/- 0.06, LVEDVI: 1.67 +/- 0.15 vs 1.70 +/- 0.17).. These results suggest that AVF rats with volume overload produced by a new multipuncture method exhibit both right- and left-side heart failure. Angiotensin II type-1 receptor antagonist as well as angiotensin converting enzyme inhibitor attenuate the development of this type of heart failure in rats.

Topics: Analysis of Variance; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta, Abdominal; Aortic Diseases; Arteriovenous Fistula; Benzimidazoles; Biphenyl Compounds; Heart Failure; Hemodynamics; Indans; Linear Models; Male; Rats; Rats, Wistar; Tetrazoles; Vena Cava, Inferior

Since dry cough has recently been recognized as a side effect of angiotensin converting enzyme (ACE) inhibitors employed in the treatment of hypertension or congestive heart failure, the incidence of dry cough in elderly patients receiving ACE inhibitors was investigated. There were 237 out-patients on either captopril, enalapril, or delapril, in August and November 1989. Questionnaires concerning dry cough and smoking were completed by 184 patients. Patients either less than 50 years of age, or with chronic pulmonary disease were excluded. The remaining 168 patients, 63 males, 105 females, with a mean age of 73 years were analyzed for the incidence of a dry cough in relation to age, sex, smoking, and type of drugs. The overall incidence of a dry cough was 21/168 (12.5%), 7/63 (11.1%) for males and 14/105 (13.3%) for females, and was less frequent with advancing age; in the 51-60 age group 4/11 (36.4%), in the 61-70 age group 5/39 (12.8%), in the 71-80 age group 9/75 (12.0%), in the 81-90 age group 3/40 (7.5%), in the 91- age group 0/3 (0%). Enalapril showed significantly higher incidence of dry cough than captopril (16/93, 17.2% vs 7/88, 8.0%, p less than 0.05). Delapril showed an incidence 4/11, 36.4%, however, 9 out of the 11 patients who were given delapril had had a history of a dry cough with captopril or enalapril, and in 4 out of these 9 patients the dry cough disappeared by replacement of captopril or enalapril by delapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cough; Enalapril; Female; Heart Failure; Humans; Hypertension; Indans; Male; Smoking; Surveys and Questionnaires

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Heart Failure; Hemodialysis, Home; Humans; Indans; Male