Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin converting enzyme inhibitors are now firmly established in the treatment of patients with chronic heart failure (CHF). Their beneficial acute and chronic hemodynamic effects are not associated with reflex tachycardia or drug tolerance. Angiotensin converting enzyme inhibitors produce symptomatic improvement and improve exercise capacity in all grades of heart failure. They also improve the prognosis of patients with severe heart failure. Quinapril is a recently introduced, nonsulfhydryl ACE inhibitor, whose intermediate half-life makes it well-suited for the treatment of patients with CHF. The acute and chronic hemodynamic effects of quinapril are similar to those of other ACE inhibitors. In a large, multicenter, randomized, placebo-controlled study of 225 patients with mild to moderate CHF, 10 to 40 mg/day quinapril significantly improved clinical status and exercise capacity in a dose-related manner. The incidence of side effects did not differ significantly from that of placebo. The initial studies with quinapril are promising and warrant further clinical investigation of this compound.
 ...
PMID:Quinapril in chronic heart failure. 226 Nov 47

In ten patients with angiographically demonstrated coronary heart disease exercise electrocardiograms were recorded before as well as two and four hours after administration of 5 or 10 mg Quinapril, an angiotensin converting enzyme inhibitor (ACEI). This reduced the sum of ST-segment depressions from 16.3 to 11.6 mV (P less than 0.001). While the heart rate remained unchanged, blood pressure fell from 147/91 to 119/79 mm Hg and the angina-free exercise time was clearly prolonged. Altogether there was a reduction of the ischaemia reaction by 35%. This perhaps speaks for an anti-anginal effect of ACEI, which could be of importance in the management of both hypertension and heart failure. In addition, the ACE inhibitors might be used as anti-angina drugs.
 ...
PMID:[Angiotensin-converting enzyme inhibitors in angina pectoris]. 335 81

The influence of angiotensin converting enzyme inhibitor therapy on elevated plasma endothelin concentrations in chronic heart failure was investigated by measuring plasma endothelin immunoreactivity in 22 patients with severe but stable chronic heart failure before and after 16 weeks of therapy with quinapril (n = 12) or captopril (n = 10). Plasma endothelin immunoreactivity in the patients (10.2 +/- 34 pg/ml) was significantly higher than a control group (5.9 +/- 1.8 pg/ml). Quinapril improved symptoms and haemodynamics but did not affect plasma endothelin immunoreactivity (11.9 +/- 2.9 pg/ml at baseline and 12.3 +/- 3.4 pg/ml after 16 weeks of quinapril). Captopril also had no effect on endothelin levels (8.1 +/- 2.9 at baseline and 8.1 +/- 3.8 pg/ml after 16 weeks of captopril). The vasodilatory effects of angiotensin converting enzyme inhibitors in heart failure are not mediated by, or associated with, changes in plasma endothelin immunoreactivity.
 ...
PMID:Effect of angiotensin converting enzyme inhibition on plasma endothelin in congestive heart failure. 818 87

Angiotensin converting enzyme (ACE) inhibitors are of proven value in patients with severe chronic heart failure (CHF). Studies of the effects of ACE inhibitors on exercise capacity and quality of life in mild CHF have produced conflicting results. We have studied the effects of quinapril, a new ACE inhibitor with a relatively short plasma half-life, in mild CHF. Once daily (o.d.) dosing was compared with twice daily (b.i.d.) dosing in a three-way cross-over, double-blind, placebo-controlled trial. Thirty-two patients (two female), mean age 59 (range 32-76) years were enrolled in three cardiology centres in the U.K. in 29 patients, and non-ischaemic in three. The mean (range) radionuclide ejection fraction was 20.4% (8%-47%). Following full familiarization with the protocol, the treadmill exercise time (modified Bruce protocol) was determined for each patient during a placebo run-in phase, and at the end of each of three 8-week double-blind treatment phases with quinapril o.d., quinapril b.i.d. (maximal total daily dose 20 mg) and placebo. Three patients were withdrawn due to adverse events while receiving quinapril (unstable angina, exacerbation of CHF and arrhythmia); there were no deaths and no patient was withdrawn due to hypotension. Mean exercise time (the primary end-point) was 65 s and 53 s longer in patients receiving quinapril o.d. and b.i.d. respectively compared to placebo (both P < 0.01, ANOVA). There was no significant period effect during the trial and no significant difference between the two quinapril dosing regimens. Quinapril had no significant effect on secondary end-points including ejection fraction, functional class and quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A multicentre, double-blind, placebo-controlled trial of quinapril in mild, chronic heart failure. 845 62

In this study 72 dogs the efficacy and safety of quinapril and captopril in the treatment of canine heart failure were found to be comparable. Differences exist between the dosage schedules of both ACE inhibitors. The recommended dosage schedule for the short acting captopril is three times daily 0.5 mg/kg bodyweight. Quinapril belongs to a newer generation of ACE inhibitors with a longer half life. Therefore a dosage of 0.5 mg/kg KGW once daily was in most cases sufficient for a successful therapy. This means that quinapril can ease the management of canine heart failure, because at least in dogs with mild to moderate heart failure the dosing interval is longer compared to captopril. Moreover, the treatment of small dogs is easier, because quinapril is available as 5 mg tablets whereas the smallest captopril tablets contain 12.5 mg agent.
 ...
PMID:[Treatment of heart failure in dogs with ACe inhibitors: comparison of quinapril and captopril]. 858 63

A drug surveillance study was performed to determine the tolerance and safety of quinapril in the treatment of patients with stage 1 or 2 hypertension. The trial was noncomparative, open-label, uncontrolled, and nonrandomized. Patients with secondary hypertension, heart failure, other heart diseases, and other serious conditions were excluded. After a washout period of 2 weeks, 752 patients (316 men and 436 women) with diastolic blood pressure (DBP) between 90 and 115 mm Hg and systolic blood pressure (SBP) between 140 and 200 mm Hg were entered into the treatment phase. The mean age of patients (+/- SD) was 53.1 +/- 11.4 years. Patients initially received 10 mg/d quinapril for 4 weeks. For nonresponders, the dosage was titrated up to a maximum of 40 mg. Active treatment continued for 12 weeks. Initial blood pressures (mean +/- SD) were DBP, 102 +/- 6.1 mm Hg, and SBP, 163 +/- 14.4 mm Hg. Final blood pressures were DBP, 83 +/- 6.5 mm Hg, and SBP, 135 +/- 11.6 mm Hg. The response rate for the therapeutic goal (DBP < 90 mm Hg and SBP < 140 mm Hg, or a reduction in SBP > or = 20 mm Hg) was 67.1%; 41 patients did not complete the study. The most common adverse events were cough, headache, and dizziness; only 10 patients (1.3%) failed to complete the study because of adverse events. Quinapril, as used in current private clinical practice, is well tolerated and effective for the treatment of patients with stage 1 or 2 hypertension.
 ...
PMID:Usefulness of low-dose, once-daily quinapril as monotherapy for patients with hypertension. 893 Apr 30

After two weeks of a wash-out run-in period with placebo, 131 patients with congestive heart failure (New York Heart Association [NYHA] class II to III) and left ventricular ejection fraction </=40% were randomly assigned to a treatment period of 4 weeks with 10 mg quinapril once daily or 12.5 mg captopril twice daily. At the end of this period, doses were titrated to 20 mg quinapril once daily or 25 mg captopril twice daily on the basis of physician judgment if there were no major adverse reactions and if blood pressure was not below 110/70 mm Hg. Clinical symptoms of heart failure were significantly relieved by both drugs at the end of a 12-week treatment period. At the beginning of the study, 23 (35%) of the 65 patients taking quinapril and 27 (41%) of the 66 patients taking captopril were in NYHA functional class III, whereas, at the end of the trial, only 4 (6%) of the patients in the quinapril group and 14 (22%; p < 0.05 versus quinapril) patients in the captopril group were classified as NYHA class III. Both drugs had a positive effect on echocardiographic parameters. There was a statistically significant increase in exercise duration in both treatment groups (quinapril, 6.2 +/- 1.8 versus 7.8 +/- 1.9 minutes, p < 0.001; captopril, 5.9 +/- 1.9 versus 7.1 +/- 2.3 minutes, p < 0.001). One patient in the quinapril group died suddenly during the study and two patients in the captopril group dropped out of the study due to persistent dry cough. No patient in the quinapril group reported side effects. Three patients in the captopril group suffered from moderate dry cough, one from taste-blindness, and another from unstable angina. The safety of the tested drugs was confirmed by laboratory tests. Quinapril was as effective as captopril in reducing signs and symptoms of heart failure and in improving the left ventricular function and the exercise capacity with few side effects.
 ...
PMID:Quinapril in patients with congestive heart failure: controlled trial versus captopril. 1042 9

It remains unknown whether angiotensin-converting enzyme (ACE) inhibition can prevent heart failure in rats with a fixed high pressure load of the left ventricle and if this effect could be attributed to normalization of contractile protein phenotype and cardiac collagen content. Rats with constriction of the ascending aorta were treated with the ACE inhibitor quinapril (6 mg kg(-1) day(-1)) (n=95) or placebo (n=96) (starting 6 weeks post surgery. Quinapril treatment improved survival markedly (P<0.0000001) during the 24 weeks observation period. There were 69 deaths with placebo and only 25 deaths with quinapril. At the end of the observation period signs of left ventricular backward failure were, however, detected in 75 rats with placebo and in 67 rats treated with quinapril (P=0.229). Cox proportional hazard model with time-dependent covariates was used to document that the effect of quinapril treatment had been dependent on time. Quinapril had no significant effect on the development of morphological signs of left ventricular dysfunction after the first 54 days of treatment. The increased isomysin V(3) proportion of hypertrophied non-failing hearts was also not affected by quinapril treatment. Irrespective of treatment, failing hypertrophied hearts were characterized by an increase in left ventricular volume (P<0.05), percentage of the 'foetal' isomyosin V(3) (P<0.05), and hydroxyproline concentration (P<0.05). While the cause of the improved survival remains unknown, quinapril did apparently not interfere with the restitution of 'foetal' gene expression of pressure overloaded cardiomyocytes leading to depressed myocardial performance, ventricular dysfunction and the consecutive myocardial fibrosis.
 ...
PMID:Heart failure development in rats with ascending aortic constriction and angiotensin-converting enzyme inhibition. 1092 73

Chronic angiotensin-converting enzyme (ACE) inhibition has been shown to improve cardiac sympathetic nerve terminal function in heart failure. To determine whether similar effects could be produced by angiotensin II AT(1) receptor blockade, we administered the ACE inhibitor quinapril, angiotensin II AT(1) receptor blocker losartan, or both agents together, to rabbits with pacing-induced heart failure. Chronic rapid pacing produced left ventricular dilation and decline of fractional shortening, increased plasma norepinephrine (NE), and caused reductions of myocardial NE uptake activity, NE histofluorescence profile, and tyrosine hydroxylase immunostained profile. Administration of quinapril or losartan retarded the progression of left ventricular dysfunction and attenuated cardiac sympathetic nerve terminal abnormalities in heart failure. Quinapril and losartan together produced greater effects than either agent alone. The effect of renin-angiotensin system inhibition on improvement of left ventricular function and remodeling, however, was not sustained. Our results suggest that the effects of ACE inhibitors are mediated via the reduction of angiotensin II and that angiotensin II plays a pivotal role in modulating cardiac sympathetic nerve terminal function during development of heart failure. The combined effect of ACE inhibition and angiotensin II AT(1) receptor blockade on cardiac sympathetic nerve terminal dysfunction may contribute to the beneficial effects on cardiac function in heart failure.
 ...
PMID:Renin-angiotensin system inhibition on noradrenergic nerve terminal function in pacing-induced heart failure. 1108 59

The cardioprotective effects of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of heart failure. Twenty-six rats were divided into two groups: one given 20 mg/kg/day quinapril (n = 11), and controls given 0.5% methylcellulose (n = 15). After oral administration for 1 month, quinapril reduced heart weight (from 1.28+/-0.05 to 0.87+/-0.02 g; p < 0.05) without changing body weight. Quinapril lowered left ventricular end-diastolic pressure (from 14.1+/-2.0 to 6.6+/-1.5 mmHg; p < 0.05) and central venous pressure (from 2.7+/-0.9 to 0.7+/-0.4 mmHg), and increased +/- dP/dt (from +2409+/-50 to +3569+/-169 mmHg/s, and from -2318+/-235 to -3960+/-203 mmHg/s; both p < 0.01). The area of myocardial fibrosis was markedly reduced by quinapril (6+/-3%) as compared with controls (29+/-6%; p < 0.01). Expression of transforming growth factor (TGF)-beta1 mRNA was markedly increased in controls as compared with age-matched normal rats. The increase in level of TGF-beta1 mRNA was significantly suppressed by quinapril (from 17.1+/-6.2 to 9.00+/-2.40; p < 0.05). These observations indicated that quinapril has cardioprotective effects on heart failure, and that the beneficial effects may be partly explained by attenuation of fibrotic response through suppression of TGF-beta1 mRNA expression.
 ...
PMID:Inhibition of progression of heart failure and expression of TGF-beta 1 mRNA in rats with heart failure by the ACE inhibitor quinapril. 1181 59


1