enalapril and Chronic-Disease

Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction and New York Heart Association class II-IV symptoms following a large, Phase III clinical trial (PARADIGM-HF) that demonstrated a 20% reduction in the combined primary end-point of death from cardiovascular cause or hospitalization for heart failure compared to enalapril. Areas covered: This review discusses the clinical efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril-valsartan in heart failure with reduced ejection fraction. Expert opinion: Based on the PARADIGM-HF trial, sacubitril-valsartan offers compelling reductions in meaningful clinical endpoints, independent of age or severity of disease. The rate of adverse events was comparable between the enalapril and sacubitril-valsartan groups, although the absolute rates are likely underestimated due to the entry criteria and run-in period. Future trials and post-market surveillance are critical to better understand the risk of angioedema in high risk populations, particularly African-Americans, as well as long-term theoretical risks including the potential for increased cerebral amyloid plaque deposition with possible development of neurocognitive disease. Current trials are underway to evaluate potential benefit in patients with heart failure with preserved ejection fraction.

Topics: Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Animals; Biphenyl Compounds; Chronic Disease; Drug Combinations; Enalapril; Heart Failure; Humans; Risk Factors; Tetrazoles; Valsartan

PARADIGM-HF study observed clinical outcomes after treatment by new drug LCZ696 or enalapril in patients with systolic chronic heart failure. It was randomized double-blind trial with LCZ696 (200 mg twice a day) and enalapril (10 mg twice a day). 8442 patients were enrolled with NYHA class II or III and left ventricular ejection fiction of 40% or less. Study drugs were added to other recommended medication. The trial was prematurely terminated after median follow-up of 27 months. The primary endpoint of the study was a combination of cardiovascular mortality and the first hospitalization for heart failure. LCZ696 drug, an inhibitor of angiotensin receptor and neprilysin (Arnie), has led to a reduction in the primary composite target by 20% (p <0.001). The treatment has decreased cardiovascular mortality by 20%, p <0.001 and hospitalization for worsening heart failure by 21%, p <0.001. LCZ696 has also decreased total mortality by 16%, p <0.001. The use of LCZ696 has been accompanied by frequent symptomatic hypotension and hypotension with a decrease in systolic blood pressure below 90 mm Hg, however, LCZ696 was less often associated with an increase in serum creatinine and serum potassium than enalapril. In addition, cough has occurred less frequently after LCZ696 than after enalapril. Discontinuation of therapy occurred in 746 patients (17.8%) treated with LCZ696 and in 833 patients (19.8%) treated with enalapril (19.8%) (p = 0.02). PARADIGM-HF study has also shown superiority of LCZ696 compared to ACE inhibitors in stable outpatients with chronic systolic heart failure NYHA stages II and III. Therefore, LCZ696 is more effective than ACE inhibitors (and angiotensin receptor blockers). Moreover, it is well tolerated. LCZ696 seems to replace the ACE inhibitors in mentioned patients. The authors also discuss the results of the first randomized study PARAMOUNT investigating LCZ696 efficacy in patients with chronic heart failure and good left ventricular ejection fraction.

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Chronic Disease; Double-Blind Method; Drug Combinations; Enalapril; Female; Heart Failure, Systolic; Hospitalization; Humans; Male; Middle Aged; Tetrazoles; Valsartan

The aims of this article were to review the rationale behind the development of combined angiotensin receptor/neprilysin inhibitors (ARNIs) for the management of chronic heart failure (HF) and to review the major clinical trials of LCZ696, the first drug in this class, that have been conducted to date.. A selected review was undertaken of publications examining the preclinical and clinical studies of drugs aimed at enhancing the activity of the endogenous natriuretic peptide system and their combination with inhibitors of the renin-angiotensin-aldosterone system, initially angiotensin-converting enzyme inhibitors (ACEIs) and more recently angiotensin II type 1 receptor blockers.. Selective neprilysin inhibitors are unlikely to be of benefit and may be associated with adverse effects when used in isolation in HF. Combining NIs with ACEIs is unsafe because of an unacceptably high prevalence of angioedema, which may be mediated by elevated levels of endogenous bradykinin. Combining a neprilysin inhibitor with an angiotensin II type 1 receptor blockers avoids the risk for angioedema. The ARNI LCZ696 was associated with greater reductions both mortality and morbidity compared with those with enalapril in a large-scale, Phase III clinical trial in patients with HF with reduced ejection fraction. Findings from a Phase II clinical trial suggested that LCZ696 may also be beneficial in HF with preserved ejection fraction, and a Phase III clinical trial of LCZ696 used for this indication is under way.. ARNIs have been described as a "game changer" by cardiologists. Based on findings from clinical trials conducted to date, there is an expectation that they will replace ACEIs as a building block of the pharmacologic treatment of chronic HF.

Topics: Aminobutyrates; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Chronic Disease; Drug Combinations; Drug Therapy, Combination; Enalapril; Heart Failure; Humans; Neprilysin; Proto-Oncogene Mas; Proto-Oncogene Proteins; Receptors, G-Protein-Coupled; Renin-Angiotensin System; Tetrazoles; Valsartan

Bisoprolol fumarate is a highly selective beta-1 receptor blocker. Bisoprolol has been extensively studied in three large mortality trials in stable chronic heart failure (CHF) patients. The CIBIS trial enrolled 641 patients and demonstrated the good tolerability of bisoprolol in a large CHF population, without evidence for any harmful effect. The CIBIS-II study was the first large randomized, double-blind, placebo-controlled study demonstrating in 2647 patients a dramatic reduction in mortality with a beta-blocking agent in CHF patients. CIBIS-III demonstrated in 1010 patients the equivalence of 2 different therapeutic strategies in de novo CHF patients. There was no difference in morbidity and mortality between sub-groups of patients receiving first bisoprolol or enalapril. These three trials also demonstrated the good tolerability of bisoprolol fumarate. Other studies were either limited in number of patients or not randomized. However, these studies confirmed the good tolerability of bisoprolol in CHF patients, even in elderly population. Bisoprolol fumarate is a selective beta-1 receptor blocker that significantly reduced morbidity and mortality in stable CHF patients. Bisoprolol is well tolerated with few significant side effects in different large trials.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Bisoprolol; Chronic Disease; Drug Administration Schedule; Drug Tolerance; Enalapril; Female; Heart Failure; Humans; Male; Randomized Controlled Trials as Topic; Treatment Outcome

This review has been focused on the new insights in the pathophysiology of mitral and aortic regurgitation and on the role of ACE-inhibitor therapy in children with chronic volume overload due to left-sided valvular lesions. Recent clinical studies show that these drugs have favorable effects when administered orally in chronic mitral and aortic regurgitation. Interestingly, the beneficial effects of ACE-inhibition regard the basic anatomic, hemodynamic and adaptive pathologic conditions related to volume overload, namely, the regurgitant orifice area and volume and ventricular remodeling. The heart is a plastic structure, constantly being altered in size, shape and composition in response to chronic volume overload. Thus, modulation of cardiac plasticity by ACE-inhibition raises the possibility of using new therapeutic strategies specifically designed to prevent and/or antagonize the mechanical disadvantages secondary to volume overload-induced cardiac remodeling. The beneficial effects of ACE-inhibition have also been observed in growing children with asymptomatic valvular regurgitation; thus, it appears that the unloading therapy has the potential of influencing the natural history of both mitral and aortic regurgitation and possibly delays surgical valve repair or replacement. These data justify early inhibition of the renin-angiotensin system in children with left ventricular volume overload due to mitral and aortic regurgitation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Aortic Valve Insufficiency; Child; Chronic Disease; Enalapril; Hemodynamics; Humans; Mitral Valve Insufficiency; Renin-Angiotensin System; Ventricular Dysfunction, Left

There is now abundant evidence that treatment with angiotensin-converting enzyme inhibitors (ACE-I) ameliorates the progression of chronic renal disease. Attention has therefore focused on the role of the renin angiotensin-aldosterone (RAA) system in mediating the development of progressive glomerulosclerosis and angiotensin II (Ang II) has been implicated in several processes thought to be important in the pathogenesis of this entity. Conversely, ACE is also known to catalyse the breakdown of bradykinin. Thus, ACE-I treatment results in elevated bradykinin levels which may cause selective efferent arteriolar dilatation, suggesting an alternative explanation for the beneficial effects of this class of drugs in chronic renal disease. The development of specific angiotensin type 1 receptor antagonists (AT1RA) has provided a means of testing the relative importance of these two mechanisms. In addition, AT1RAs differ from ACE-I in their effect on the RAA system in other aspects which may represent therapeutic advantages. This paper reviews studies which have compared ACE-I and AT1RAs in several rat models of chronic renal disease. Most have found similar beneficial effects including amelioration of proteinuria and glomerulosclerosis, which suggests that the effects of ACE-I are due to a reduction in Ang II activity and not due to increased levels of bradykinin. One long-term study has suggested greater renal protection with candesartan than with enalapril. However, conclusions as regards the relative efficacy of these two groups of agents in ameliorating the progression of chronic renal disease await the results of further long-term studies.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Bradykinin; Chronic Disease; Disease Models, Animal; Enalapril; Follow-Up Studies; Glomerulosclerosis, Focal Segmental; Hypertension, Renal; Peptidyl-Dipeptidase A; Rats; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin; Tetrazoles; Treatment Outcome

Topics: Captopril; Chronic Disease; Clinical Trials as Topic; Enalapril; Evaluation Studies as Topic; Heart Failure; Humans; Multicenter Studies as Topic; Placebos; Random Allocation

In the Studies of Left Ventricular Dysfunction (SOLVD) treatment trial, similar clinical benefits were observed between starting doses of enalapril and the target dose achieved by postrandomization up-titration. In our current analysis, protecting the randomization, we examined the early effects of starting doses of enalapril.. There were 2569 patients with mild-to-moderate chronic heart failure with reduced ejection fraction (ejection fraction ≤35%) randomized to receive starting doses (5-10 mg/day) of placebo (n = 1284) or enalapril (n = 1285). At day 14, both study drugs were blindly up-titrated to the target dose (20 mg/day). Overall, 96% (2458/2569) of the patients returned for dose up-titration, which was achieved in 59% (1444/2458), 48% (696/1444) of whom were in the enalapril group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes in the enalapril group were estimated.. HRs (95% CIs) for all-cause mortality, heart failure hospitalization, and the combined endpoint of heart failure hospitalization or all-cause mortality at 14 days after randomization were 0.80 (0.32-2.03), 0.63 (0.35-1.12), and 0.65 (0.39-1.06), respectively. Corresponding HRs (95% CIs) at 30 days were 0.82 (0.41-1.67), 0.43 (0.27-0.68), and 0.43 (0.27-0.68), respectively. The magnitude of these early effects of starting doses of enalapril is similar to its previously reported long-term effects at the target dose.. These data suggest that in stable ambulatory patients with heart failure with reduced ejection fraction, the magnitude of the early effect of starting doses of enalapril is similar to that observed during longer-term therapy with the target doses of the drug.

Topics: Aged; Chronic Disease; Dose-Response Relationship, Drug; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged

The angiotensin-converting enzyme inhibitor enalapril is commonly used to treat chronic heart failure in children. Because some children are unable to swallow capsules or tablets, a new, age-appropriate, orodispersible minitablet (ODMT) containing 1 mg of enalapril was developed within the EU-funded LENA (Labeling of Enalapril from Neonates up to Adolescents) consortium. In order to support the clinical evaluation of this new formulation in children, a relative bioavailability study was performed in healthy adults, comparing the bioavailability of enalapril in the ODMT with that of a reference product (RP) Renitec, a registered standard enalapril tablet formulation. In this open-label, randomized 3-way crossover study, 24 healthy subjects received a 10-mg enalapril dose administered as (1) 2 × 5-mg tablets of the RP swallowed with water, (2) 10 × 1-mg ODMT swallowed with water, and (3) 10 × 1 mg ODMT dispersed on the tongue. When the relative bioavailability of the ODMT formulation swallowed with water was compared with that of the RP, the estimated 90%CIs for the ratio of area under the concentration-time curve (AUC

Topics: Administration, Oral; Adult; Angiotensin-Converting Enzyme Inhibitors; Biological Availability; Chronic Disease; Cross-Over Studies; Dosage Forms; Enalapril; Female; Healthy Volunteers; Heart Failure; Humans; Male; Middle Aged; Safety; Tablets; Therapeutic Equivalency

We aimed to assess the cost effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) for the treatment of individuals with chronic heart failure and reduced-ejection fraction (HFrEF) from the perspective of the Swiss health care system.. The cost-effectiveness analysis was implemented as a lifelong regression-based cohort model. We compared sacubitril/valsartan with enalapril in chronic heart failure patients with HFrEF and New York-Heart Association Functional Classification II-IV symptoms. Regression models based on the randomised clinical phase III PARADIGM-HF trials were used to predict events (all-cause mortality, hospitalisations, adverse events and quality of life) for each treatment strategy modelled over the lifetime horizon, with adjustments for patient characteristics. Unit costs were obtained from Swiss public sources for the year 2014, and costs and effects were discounted by 3%. The main outcome of interest was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life years (QALYs) gained. Deterministic sensitivity analysis (DSA) and scenario and probabilistic sensitivity analysis (PSA) were performed.. In the base-case analysis, the sacubitril/valsartan strategy showed a decrease in the number of hospitalisations (6.0% per year absolute reduction) and lifetime hospital costs by 8.0% (discounted) when compared with enalapril. Sacubitril/valsartan was predicted to improve overall and quality-adjusted survival by 0.50 years and 0.42 QALYs, respectively. Additional net-total costs were CHF 10 926. This led to an ICER of CHF 25 684. In PSA, the probability of sacubitril/valsartan being cost-effective at thresholds of CHF 50 000 was 99.0%.. The treatment of HFrEF patients with sacubitril/valsartan versus enalapril is cost effective, if a willingness-to-pay threshold of CHF 50 000 per QALY gained ratio is assumed.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biphenyl Compounds; Chronic Disease; Cost-Benefit Analysis; Drug Combinations; Enalapril; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Quality-Adjusted Life Years; Stroke Volume; Switzerland; Tetrazoles; Valsartan

Compared to heart failure patients with higher systolic blood pressure (SBP), those with lower SBP have a worse prognosis. To make matters worse, the latter patients often do not receive treatment with life-saving therapies that might lower blood pressure further. We examined the association between SBP and outcomes in the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with an angiotensin-converting enzyme (ACE) inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF), as well as the effect of sacubitril/valsartan, compared with enalapril, according to baseline SBP.. We analysed the effect of treatment on SBP and on the primary composite outcome (cardiovascular death or heart failure hospitalization), its components and all-cause death. We examined baseline SBP as a categorical (<110, 110 to < 120, 120 to < 130, 130 to < 140 and ≥140 mmHg) and continuous variable, as well as average in-trial SBP and time-updated SBP.. All-cause and cardiovascular mortality rates were highest in patients with the lowest SBP whereas there was a U-shaped relationship between SBP and the rate of heart failure hospitalization. The benefit of sacubitril/valsartan over enalapril was consistent across all baseline SBP categories for all outcomes. For example, the sacubitril/valsartan versus enalapril hazard ratio for the primary endpoint was 0.88 (95%CI 0.74-1.06) in patients with a baseline SBP <110 mmHg and 0.81 (0.65-1.02) for those with a SBP ≥140 mmHg (P for interaction = 0.55). Symptomatic hypotension, study drug dose-reduction and discontinuation were more frequent in patients with a lower SBP.. In PARADIGM-HF, patients with lower SBP at randomization, notably after tolerating full doses of both study drugs during a run-in period, were at higher risk but generally tolerated sacubitril/valsartan and had the same relative benefit over enalapril as patients with higher baseline SBP.

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Blood Pressure; Chronic Disease; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Hospitalization; Humans; Hypotension; Male; Neprilysin; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan

Among patients with chronic heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction.. After a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy). The primary composite outcome was death from cardiovascular causes or hospitalization for heart failure.. After a median follow-up of 36.6 months, the primary outcome occurred in 770 patients (32.9%) in the combination-therapy group and in 808 (34.6%) in the enalapril group (hazard ratio, 0.93; 95% confidence interval [CI], 0.85 to 1.03). The primary outcome occurred in 791 patients (33.8%) in the aliskiren group (hazard ratio vs. enalapril, 0.99; 95% CI, 0.90 to 1.10); the prespecified test for noninferiority was not met. There was a higher risk of hypotensive symptoms in the combination-therapy group than in the enalapril group (13.8% vs. 11.0%, P=0.005), as well as higher risks of an elevated serum creatinine level (4.1% vs. 2.7%, P=0.009) and an elevated potassium level (17.1% vs. 12.5%, P<0.001).. In patients with chronic heart failure, the addition of aliskiren to enalapril led to more adverse events without an increase in benefit. Noninferiority was not shown for aliskiren as compared with enalapril. (Funded by Novartis; ATMOSPHERE ClinicalTrials.gov number, NCT00853658.).

Topics: Aged; Amides; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Follow-Up Studies; Fumarates; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Renin; Stroke Volume; Treatment Failure

Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting.. We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35%, without ACEI, β-blocker or angiotensin-receptor-blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6-24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death.. During the monotherapy phase, 8 of 23 deaths in the bisoprolol-first group were sudden, compared to 16 of 32 in the enalapril-first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21-1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29-1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51-1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71-16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92-7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99-5.75; P= 0.053. There were no significant between-group differences in any other fatal events.. Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol-first cohort.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Bisoprolol; Chronic Disease; Death, Sudden, Cardiac; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Hospitalization; Humans; Male

Dual blockade of the renin-angiotensin system (RAS) has been claimed to have a specific renal protective effect in chronic kidney disease (CKD). The present short-term study reports on the feasibility of dual blockade in a consecutive group of patients with CKD stage 3-5.. Forty-seven CKD patients, mean age 59 years, with mean estimated glomerular filtration rate (GFR) 26 ml/min/1.73 m(2) (range 13-49) and blood pressure (BP) 133/78 mmHg, were block randomized in an open study to 16 weeks of monotherapy with increasing doses of RAS blockade aiming at enalapril 20 mg o.d. or candesartan 16 mg o.d. Thereafter, the complementary drug was added in incremental doses over a period of 5 weeks aiming at combined enalapril 20 mg and candesartan 16 mg for 3 weeks. Seventy-five percent of the patients were known to be RAS blockade tolerant. Blood samples and BP were measured every 2-3 weeks. Doses of study medication were reduced in case of hyperkalemia >5.5 mmol/l, a sustained rise in p-creatinine >30% or symptomatic hypotension.. Twenty-one patients (45%) did not tolerate dual blockade in aimed dosages due to unacceptable p-creatinine increase (n = 12, including two study withdrawals), hypotension (n = 6), general discomfort (n = 2) or unmanageable hyperkalemia (n = 1). Hyperkalemia >5.5 mmol/l was seen in seven patients (15%). The reduced-dose group had baseline lower eGFR and diastolic BP.. Forty-five percent of CKD stage 3-5 patients did not tolerate dual RAS blockade with 20 mg enalapril and 16 mg candesartan daily, primarily due to loss of renal function or hypotension. Hyperkalemia could be managed in most patients. Caution is recommended when giving this treatment to patients with advanced CKD.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Chronic Disease; Disease Progression; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enalapril; Feasibility Studies; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Renin-Angiotensin System; Tetrazoles

Our objective was to investigate the effects and tolerability of fixed-dose combination therapy on blood pressure and LDL in adults without elevated blood pressure or lipid levels.. This was a double-blind randomised placebo-controlled trial in residents of Kalaleh, Golestan, Iran. Following an 8-week placebo run-in period, 475 participants, aged 50 to 79 years, without cardiovascular disease, hypertension or hyperlipidaemia were randomised to fixed-dose combination therapy with aspirin 81 mg, enalapril 2.5 mg, atorvastatin 20 mg and hydrochlorothiazide 12.5 mg (polypill) or placebo for a period of 12 months. The primary outcomes were changes in LDL-cholesterol, systolic and diastolic blood pressure and adverse reactions. Analysis was by intention-to-treat basis.. At baseline, there were differences in systolic blood pressure (6 mmHg). Taking account of baseline differences, at 12 months, polypill was associated with statistically significant reductions in blood pressure (4.5/1.6 mmHg) and LDL-cholesterol (0.46 mmol/l). The study drug was well tolerated, but resulted in the modest reductions in blood pressure and lipid levels.. The effects of the polypill on blood pressure and lipid levels were less than anticipated, raising questions about the reliability of the reported compliance. There is a case for a fully powered trial of a polypill for the prevention of cardiovascular disease.

Topics: Aged; Anticholesteremic Agents; Antihypertensive Agents; Aspirin; Atorvastatin; Blood Pressure; Cardiovascular Diseases; Cholesterol, LDL; Chronic Disease; Double-Blind Method; Drug Combinations; Enalapril; Female; Heptanoic Acids; Humans; Hydrochlorothiazide; Male; Middle Aged; Pilot Projects; Platelet Aggregation Inhibitors; Pyrroles; Risk Factors; Tablets

Angiotensin II and insulin resistance (IR) have clinical implications in the pathophysiology of chronic heart failure (CHF). However, it is still unclear whether the combination of an angiotensin-receptor blocker and angiotensin-converting enzyme inhibitor (ACEI) improves IR in CHF patients who do not receive β-blockers. Thus, the aim of the present study was to evaluate the effects of losartan on glucose metabolism and inflammatory cytokines in CHF patients treated with ACEI but not β-blockers.. The effect of losartan treatment for 16 weeks on IR was analyzed in 16 CHF patients in a randomized crossover trial. Insulin level and homeostasis model IR index (HOMA-IR) decreased significantly (P<0.05), but fasting plasma glucose did not change significantly. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 levels were significantly decreased with losartan (P<0.05). Furthermore, the changes in IL-6 and MCP-1 levels were significantly correlated with the reduction in HOMA-IR (P<0.05), but the change in TNF-α levels was not significantly correlated.. The addition of losartan to ACEI therapy improved IR and decreased inflammatory cytokines in CHF patients who did not receive β-blockers.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Blood Glucose; Chemokine CCL2; Chronic Disease; Cross-Over Studies; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Imidazolidines; Inflammation Mediators; Insulin; Insulin Resistance; Interleukin-6; Japan; Lisinopril; Losartan; Male; Middle Aged; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

Combination therapy with angiotensin II Type I receptor blocker 50 mg of losartan and a fixed combination of losartan (50 mg)/hydrochlorothiazide (12.5 mg) was administered to hypertensive patients with Stage 3 - 4 chronic kidney disease to investigate its renoprotective effect.. Subjects already being administered the angiotensin I-converting enzyme inhibitor enalapril and losartan 100 mg daily were enrolled in this open-labeled trial (n = 40). Administration of 100 mg losartan twice daily was replaced with losartan (50 mg)/hydrochlorothiazide (12.5 mg) once daily after the morning meal and losartan at 50 mg once daily after the evening meal for the 24-week study period.. The mixture of losartan/hydrochlorothiazide significantly reduced systolic and diastolic blood pressures by 14.7 and 7.4 mmHg, respectively, compared with the baseline values. No significant changes were observed in the serum creatinine levels and estimated glomerular filtration rate. The urinary protein/creatinine ratio was, however, significantly decreased. Similarly, the regression line of 1/serum creatinine level was significantly increased after administration of losartan/hydrochlorothiazide. None of the patients exhibited a significant increase in the occurrence of adverse effects.. Our results demonstrated that a low dose of hydrochlorothiazide had a renoprotective effect due to its blood pressure-lowering effect. We accordingly propose that a low dose of hydrochlorothiazide should be administered to those patients in whom the blood pressure is not well controlled by intensive renin-angiotensin system inhibition therapy using the maximum recommended doses of angiotensin II Type I receptor blockers and angiotensin I-converting enzyme inhibitors.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Chronic Disease; Creatinine; Drug Administration Schedule; Drug Combinations; Enalapril; Female; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Hypertension; Kidney Diseases; Losartan; Male; Middle Aged

To assess the clinical effects and safety profile of initial monotherapy with either bisoprolol or enalapril in elderly patients with heart failure (HF).. In CIBIS III, 1010 patients with mild to moderate HF and age>or=65 years were randomized to monotherapy with either bisoprolol or enalapril for 6 months.. Bisoprolol had a similar effect as enalapril on the combined end-point of all-cause mortality or hospitalization (HR 1.02; p=0.90), as well as on each of the individual end-points. A trend towards fewer sudden deaths was observed with bisoprolol (NS). On the other hand, more cases of worsening HF requiring hospitalization or occurring while in hospital were observed in the bisoprolol group (HR 1.67; p=0.03). The two groups were similar with regard to treatment cessations and early introduction of the second drug.. Bisoprolol and enalapril had a similar effect on the combined end-point of mortality or hospitalization during 6 months monotherapy. However, more worsening HF events were observed in the bisoprolol group.

Topics: Aged; Antihypertensive Agents; Bisoprolol; Blood Pressure; Bradycardia; Chronic Disease; Cough; Drug Administration Schedule; Enalapril; Female; Heart Failure; Heart Rate; Humans; Hypotension; Kaplan-Meier Estimate; Male; Prospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; Withholding Treatment

The long-term effect of beta-blockade on the plasma levels of natriuretic peptides BNP and its N-terminal counterpart, NT-proBNP, as risk markers in heart failure (HF) is obscure.. Stable systolic HF patients from the CARMEN study were divided in groups matching their randomised treatment allocation: Carvedilol, enalapril or carvedilol+enalapril. Changes in BNP and NT-proBNP from baseline to 6 months maintenance visit were evaluated in each treatment arm. Furthermore, the prognostic value of BNP and NT-proBNP during monotherapy with carvedilol was assessed with univariate Cox proportional hazards models using a combined endpoint of all cause mortality and cardiovascular hospitalisation.. NT-proBNP and BNP were significantly reduced after six months treatment with enalapril (NT-proBNP 1,303 to 857 pg/ml (P < 0.001), BNP 119 to 85 pg/ml (P < 0.001)) or carvedilol+enalapril (NT-proBNP 1,223 to 953 pg/ml (P = 0.003), BNP 117 to 93 pg/ml (P = 0.01)). In contrast, no change was observed in the carvedilol group (NT-proBNP 907 to 1,082 pg/ml (P = 0.06), BNP 114 to 130 pg/ml (P = 0.15). The prognostic value of NT-proBNP and BNP was maintained in the carvedilol group (NT-proBNP HR 1.018 95% CI (1.005-1.032), BNP 1.171 (1.088-1.260)).. Treatment of HF patients with carvedilol alone does not reduce levels of natriuretic peptides, but treatment with enalapril does. Both BNP and NT-proBNP predict death and hospitalisation in HF patients treated with carvedilol for six months. The clinical implication of our results is that NT-proBNP and BNP can be used as risk markers of death and cardiovascular hospitalisations in systolic HF patients receiving carvedilol without ACE inhibition.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Enalapril; Europe; Female; Heart Failure, Systolic; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Propanolamines; Proportional Hazards Models; Risk Assessment; Time Factors; Treatment Outcome

In patients with chronic heart failure (CHF), it remains unclear whether perindopril is more cardioprotective than enalapril.. Forty-five stable CHF outpatients undergoing conventional therapy including enalapril therapy were randomized to 2 groups [group I (n=24): continuous enalapril treatment; group II (n=21): enalapril was changed to perindopril]. Cardiac sympathetic nerve activity was evaluated using cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and 6 months after treatment. There was no difference in baseline characteristics between the 2 groups. In group I, there were no changes in MIBG parameters, left ventricular ejection fraction (LVEF) or plasma level of brain natriuretic peptide (BNP). In contrast, in group II the delayed heart/mediastinum count ratio was significantly increased (2.0+/-0.07 vs 2.15+/-0.07, p=0.013) and the washout rate was significantly decreased (33.0+/-1.4 vs 30.5+/-1.2, p=0.030) after 6 months compared with the baseline value. In addition, LVEF was significantly increased and the plasma BNP level was significantly decreased.. These findings suggest that for the treatment of CHF, perindopril is superior to enalapril with respect of cardiac sympathetic nerve activity and BNP.

Topics: 3-Iodobenzylguanidine; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Enalapril; Female; Follow-Up Studies; Heart; Heart Failure; Humans; Iodine Radioisotopes; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Perindopril; Radionuclide Imaging; Risk Factors; Stroke Volume; Sympathetic Nervous System; Treatment Outcome

The objective of this study was to determine the safety and efficacy of renin-angiotensin system (RAS) inhibitors and beta-blockers in chronic Chagas cardiomyopathy.. Chronic Chagas cardiomyopathy causes substantial morbidity and mortality in Latin America. Whether RAS inhibitors and beta-blockers are safe and beneficial has been challenged because of the lack of formal trials.. We conducted a double-blind, placebo-controlled, and randomized trial in 42 patients with Trypanosoma cruzi infection and cardiomyopathy. All patients received enalapril (up-titrated to 20 mg BID) and spironolactone (25 mg QD). Subsequently, the patients were randomly assigned to receive placebo (n = 20) or carvedilol up-titrated to 25 mg BID (n = 19). The primary end points were change in left ventricular ejection fraction (LVEF) after RAS inhibition and that after the addition of carvedilol. The secondary end points were changes in other echocardiographic parameters, Framingham score, quality of life (36-item Short-Form Health Survey), New York Heart Association class, radiographic indices, brain natriuretic peptide levels, and chemokines as well as safety end points.. Optimization of RAS inhibition was safe, hemodynamically well tolerated, and associated with improvements in Framingham score (P = .001) and quality of life as well as reductions in the cardiothoracic index (P = .002), brain natriuretic peptide level (P = .032), and RANTES (regulated on activation, normal T expressed and secreted) level (P = .001). Left ventricular ejection fraction increased by 2.3% (P = .25); in patients with an LVEF < or = 45% at baseline, it increased by 2.8% (P = .017). Treatment with carvedilol was associated with a trend toward an increase in LVEF (absolute difference between groups, 2.3%; P = .094). The addition of carvedilol was safe, hemodynamically well tolerated, and not associated with symptomatic bradycardia.. In patients with chronic Chagas cardiomyopathy, optimization of treatment with enalapril and spironolactone and subsequent addition of carvedilol were safe and associated with benefits in cardiac function and clinical status. Larger trials are needed to show effects on mortality and/or hospitalization.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Carbazoles; Carvedilol; Chagas Cardiomyopathy; Chronic Disease; Double-Blind Method; Enalapril; Female; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Propanolamines; Renin-Angiotensin System; Spironolactone

Chronic kidney disease (CKD), anemia, and declining kidney function are recognized as risk factors for adverse outcomes in patients with heart failure. This analysis was conducted to evaluate whether anemia is a risk factor for kidney function decrease in patients with heart failure. Data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized trial of enalapril versus placebo in patients with ejection fractions or=6 ml/min/1.73 m(2)/year. Anemia was defined as baseline hematocrit <36%. Multivariate logistic regression weighted by the number of GFR assessments was used to test the relation between anemia and rapid decrease. We also evaluated whether CKD (baseline GFR

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Cardiac Output, Low; Chronic Disease; Cohort Studies; Creatinine; Diabetes Complications; Double-Blind Method; Enalapril; Female; Follow-Up Studies; Glomerular Filtration Rate; Hematocrit; Humans; Hypertension; Kidney; Kidney Diseases; Male; Middle Aged; Placebos; Risk Factors; Stroke Volume

Heart failure (HF) treatment guidelines of the ESC recommend ACE-inhibitors (ACE-I) as first-line treatment and beta-blockers added if patients remain symptomatic. CARMEN explored the need for combined treatment for remodelling and order of introduction by comparing the ACE-I enalapril against carvedilol and their combination.. In a parallel-group, 3-arm study of 18 months duration, 572 mild heart failure patients were randomly assigned to carvedilol (N = 191), enalapril (N = 190) or their combination (N = 191). In the latter, carvedilol was up-titrated before enalapril. Left ventricular (LV) remodelling was assessed by transthoracic echocardiography (biplane, modified Simpson) at baseline and after 6, 12 and 18 months of maintenance therapy. Primary comparisons considered the change in LV end-systolic volume index (LVESVI) from baseline to month 18 between the combination and enalapril, and between carvedilol and enalapril.. In the first primary comparison, LVESVI was reduced by 5.4 ml/m2 (p = 0.0015) in favour of combination therapy compared to enalapril. The second primary comparison tended to favour carvedilol to enalapril (NS). In the within treatment arm analyses, carvedilol significantly reduced LVESVI by 2.8 ml/m2 (p = 0.018) compared to baseline, whereas enalapril did not. LVESVI decreased by 6.3 ml/m2 (p = 0.0001) with combination therapy. All three arms showed similar safety profiles and withdrawal rates.. CARMEN is the first study to demonstrate that early combination of ACE-I and carvedilol reverses LV remodelling in patients with mild to moderate HF and LV systolic dysfunction. The results of the CARMEN study support a therapeutic strategy in which the institution of beta-blockade should not be delayed.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Carbazoles; Carvedilol; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Propanolamines; Ventricular Remodeling

Angiotensin-converting-enzyme (ACE) inhibitors and beta-blockers are standard therapy for chronic heart failure (CHF). beta-blockers are recommended to be initiated after ACE-inhibitors, but this order is not evidence based. The initiation order may be important since many, especially elderly CHF patients cannot tolerate target doses of both. Data suggest that beta-blockers may be more important to CHF patients than ACE-inhibitors, especially in early stages of CHF.. To compare the effect on combined death or hospitalisation of initial monotherapy with either bisoprolol or enalapril, followed by combination therapy.. One-thousand CHF patients without ACE-inhibitor, beta-blocker or angiotensin-receptor-blocker therapy will be randomised 1:1 to monotherapy with either enalapril or bisoprolol for 6 months, followed by combined therapy for 6-18 months. The primary objective is to show non-inferiority for bisoprolol-first vs. enalapril-first regarding combined death or hospitalisation. If that is shown, superiority for bisoprolol-first will be tested.. If the trial shows non-inferiority for bisoprolol-first vs. enalapril-first, the first CHF therapy may be chosen based on individual judgement in each patient. If bisoprolol-first is superior to enalapril-first, a beta-blocker should be given prior to an ACE-inhibitor in CHF, and the paradigm of testing CHF compounds against a background of ACE-inhibitor therapy will be challenged.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Bisoprolol; Blood Pressure; Chronic Disease; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Heart Rate; Humans; Male; Practice Guidelines as Topic; Prospective Studies; Stroke Volume; Survival Analysis; Treatment Outcome

Experimental studies suggest that angiotensin-converting enzyme (ACE) inhibitors with high tissue affinity confer a greater degree of vascular renin-angiotensin system suppression than those with low tissue affinity despite similar suppression of the circulating renin-angiotensin system. To test this hypothesis in a clinical setting, we randomized subjects with chronic heart failure to receive the low tissue affinity ACE inhibitor enalapril or the high tissue affinity ACE inhibitor trandolapril, and assessed the degree of circulating and vascular renin-angiotensin system suppression. Vascular renin-angiotensin system suppression was determined by measuring the pressor response to intravenous injections of angiotensin I. Circulating renin-angiotensin system suppression was determined by measuring plasma angiotensin II. Vascular and circulating renin-angiotensin system suppression, endothelial function (flow-mediated vasodilation), and maximal exercise capacity (peak oxygen uptake) were assessed after a 4-week run-in period on open-label enalapril 40 mg/day and after 8 weeks of randomized double-blind treatment with enalapril 40 mg/day or trandolapril 4 mg/day. Twenty-six men and 4 women (mean age 52 +/- 11 years; mean left ventricular ejection fraction 25 +/- 9%; New York Heart Association class II [n = 16] and III [n = 14]) were studied. After a 2-month randomized treatment period, vascular renin-angiotensin system suppression, circulating renin-angiotensin system suppression, endothelial function, and exercise capacity did not differ between subjects treated with enalapril and those treated with trandolapril. Despite substantial differences in the tissue affinity of enalapril and trandolapril, the degree of vascular renin-angiotensin system suppression achieved with these agents did not differ in subjects with chronic heart failure during long-term therapy.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Double-Blind Method; Enalapril; Endothelium, Vascular; Exercise Tolerance; Female; Heart Failure; Humans; Indoles; Male; Middle Aged; Renin-Angiotensin System

The renin-angiotensin system is thought to be involved in the progression of chronic renal diseases of both diabetic and non-diabetic origin. It has been confirmed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) reduce urinary protein excretion and attenuate the development of renal injury. Clinical data comparing the renal effects of ACEIs and ARBs, either singly or in combination, are scarce and usually concern the use of standard or high doses.. This was a prospective, randomized, 9-month study of the effects of low doses of losartan (25 mg; n = 18) versus enalapril (10 mg; n = 18) versus the combination of losartan (25 mg) and enalapril (10 mg) (n = 16) on proteinuria, kidney function and metabolic profile in 54 patients with biopsy-proven chronic glomerulonephritis, hypertension and normal or slightly impaired kidney function. The clinical evaluation and laboratory tests were performed before treatment (baseline) and after 3 and 9 months of therapy.. After 3 months, significant decreases in proteinuria were observed in all groups: losartan, 22.6% (p = 0.02); enalapril, 43% (p = 0.012); and combined therapy, 63% (p = 0.001). This anti-proteinuric effect was even greater after 9 months of therapy: losartan, 44.2% (p = 0.02); enalapril, 49.6% (p = 0.02); and combined therapy, 51% (p = 0.003). There was no significant difference between losartan and enalapril with respect to their impact on proteinuria level. Proteinuria reduction was significantly greater in patients receiving combined therapy in comparison with losartan treatment after 3 months of therapy (p = 0.02). Creatinine clearance and serum creatinine were stable during the entire study period in all patients. No significant changes in lipids, serum uric acid or protein levels were observed.. These results indicate that proteinuria is reduced by low doses of losartan or enalapril. The combination of these drugs seems to be beneficial and may offer an additional renoprotective effect. This needs to be confirmed in a study with a larger sample size.

Topics: Adult; Analysis of Variance; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Enalapril; Female; Follow-Up Studies; Glomerulonephritis; Humans; Kidney Function Tests; Losartan; Male; Middle Aged; Prospective Studies; Reference Values; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome

To study echocardiographic parameters of left ventricular systolic function and valvar regurgitation under pharmacological influence in mildly symptomatic patients with chronic mitral regurgitation (MR).. We carried out a double-blind placebo controlled study in 12 patients with MR, mean aged 12.5 years old, who were randomized in 4 phases: A) digoxin; B) enalapril; C) digoxin + enalapril; D) placebo. The medication was administered for 30 days in each phase, and the following variables were analyzed: shortening and ejection fractions, wall stress index of left ventricle, left ventricular meridional end-systolic wall stress, Doppler-derived mean rate of left ventricular pressure rise (mean dP/dt), stroke volume and MR jet area. The clinical variables analysed were heart rate and systemic arterial pressure.. No significant variation was observed in the clinical variables analysed. The shortening and ejection fraction, the mean dP/dt and stroke volume significantly increased and the wall stress index of left ventricle, the meridional left ventricular end systolic wall stress and the mitral regurgitation jet area decreased in the phases with medication as compared with that in the placebo phase.. The parameters of left ventricular systolic function improved significantly and the degree of MR decreased with the isolated administration of digoxin or enalapril in mildly symptomatic patients with chronic MR. The combination of the drugs, however, did not show better results.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Child; Chronic Disease; Digoxin; Double-Blind Method; Enalapril; Female; Humans; Male; Mitral Valve Insufficiency; Systole; Time Factors; Ultrasonography; Ventricular Function, Left

Combined inhibition of the angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) may produce greater benefits in heart failure than ACE inhibition alone.. We randomly assigned 5770 patients with New York Heart Association class II to IV heart failure to double-blind treatment with either the ACE inhibitor enalapril (10 mg BID, n=2884) or to the ACE-NEP inhibitor omapatrilat (40 mg once daily, n=2886) for a mean of 14.5 months. The primary end point-the combined risk of death or hospitalization for heart failure requiring intravenous treatment--was used prospectively to test both a superiority and noninferiority hypothesis (based on the effect of enalapril in the Studies of Left Ventricular Dysfunction [SOLVD] Treatment Trial). A primary end point was achieved in 973 patients in the enalapril group and in 914 patients in the omapatrilat group (hazard ratio 0.94; 95% CI: 0.86 to 1.03, P=0.187)--a result that fulfilled prespecified criteria for noninferiority but not for superiority. The omapatrilat group also had a 9% lower risk of cardiovascular death or hospitalization (P=0.024) and a 6% lower risk of death (P=0.339). Post hoc analysis of the primary end point with the definition used in the SOLVD Treatment Trial (which included all hospitalizations for heart failure) showed an 11% lower risk in patients treated with omapatrilat (nominal P=0.012).. Omapatrilat reduces the risk of death and hospitalization in chronic heart failure but was not more effective than ACE inhibition alone in reducing the risk of a primary clinical event. Between-group differences in favor of omapatrilat observed in secondary and post hoc analyses warrant further study.

Topics: Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Disease-Free Survival; Double-Blind Method; Enalapril; Endpoint Determination; Female; Heart Failure; Humans; Male; Middle Aged; Neprilysin; Protease Inhibitors; Pyridines; Thiazepines

It is possible that vasodilator therapy may retard left ventricular (LV) dilatation and functional deterioration in chronic mitral regurgitation (MR). The study objectives were to evaluate comparatively the efficacy of nicorandil (a new, balanced vasodilator) and enalapril therapy on LV volume, mass and function in mildly symptomatic, chronic rheumatic severe MR.. Eighty-seven mildly symptomatic rheumatic patients with severe MR were enrolled in this prospective, randomized study. All patients underwent serial echocardiography study at entry, and again at six months. Eighty patients completed the study.. At six months, the nicorandil and enalapril patient groups each had a significant reduction in LV end-systolic volume index (57.4 +/- 24.8 versus 43.2 +/- 20.7 ml/m2, p = 0.003; 50.0 +/- 19.0 versus 40.4 +/- 14.2 ml/m2, p = 0.006, respectively) and LV mass index (218.0 +/- 88.0 versus 188.0 +/- 76.0 g/m2, p = 0.05; 217.2 +/- 48.0 versus 186.2 +/- 45.0 g/m2, p = 0.002 respectively). Both nicorandil and enalapril caused significant improvement in ejection fraction (63.8 +/- 7.0 versus 71.0 +/- 6.7%, p <0.0001; 63.2 +/- 6.9 versus 67.5 +/- 6.4%, p = 0.002, respectively) and a reduction in LV end-systolic stress (152.9 +/- 29.0 versus 126.0 +/- 25.0 dyne/cm2, p = 0.001; 150.0 +/- 30.2 versus 138.0 +/- 29.0 dyne/cm2, p = 0.002, respectively). However, nicorandil caused a greater reduction in absolute LV end-systolic volume index (13.3 +/- 10.1 versus 9.6 +/- 5.9 ml/m2, p = 0.02), and a greater improvement in absolute ejection fraction (7.2 +/- 4.7 versus 4.2 +/- 2.6%, p = 0.0005) than enalapril.. It is concluded that nicorandil is equivalent to enalapril in improving LV volume, mass, end-systolic stress and ejection fraction in mildly symptomatic chronic rheumatic severe mitral regurgitation over a period of six months.

Topics: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Enalapril; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Mitral Valve Insufficiency; Nicorandil; Prospective Studies; Rheumatic Diseases; Ultrasonography; Vasodilator Agents; Ventricular Function, Left

To study ednit (ACE inhibitor) effectiveness in the treatment of portal hypertension in patients with chronic hepatitis (CH) and hepatic cirrhosis (HC).. The examination of 87 patients with active CH and 54 patients with HC at the preascytic stage included two-dimentional ultrasonic scanning of the abdominal organs with doppler fluometry of the vessels in the territory of the portal vein, tetrapolar rheohepatography, ultrasound investigation, angiography of the abdominal vessels. The patients received combined therapy with ednit in a dose 5 mg twice a day for at least 5 weeks.. Patients with active CH and HC having portal hypertension treated with adjuvant ednit in the above dose achieved marked clinicobiochemical remission quicker, portal-hepatic circulation improved.. The addition of ednit to therapy of active CH and HC with portal hypertension is effective as it lowers total peripheral vascular resistance which eventually results in a fall of pressure in the territory of the portal vein and improvement of hepatic circulation. The highest effect is reached in administration of 5 mg twice for 24 hours.

Topics: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Chronic Disease; Enalapril; Female; Hepatitis, Viral, Human; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged

First-dose hypotension refers to an observed reduction in blood pressure after the administration of the first dose of ACE inhibitors in patients with congestive heart failure.. To compare the first-dose responses of low-dose enalapril and perindopril in patients with stable symptomatic chronic heart failure.. Single blind, randomised, multicenter, parallel, prospective study. Patients (N=298) with chronic heart failure due to ischemic heart disease or dilated cardiomyopathy, NYHA II-IV, ejection fraction<40%, age>18 years, naive to ACE inhibitors or ATI-receptor blocker, were randomised to receive a single dose of 2. 5 mg enalapril or 2.0 mg perindopril. Baseline laboratory and clinical examinations were performed before entry into the study. Ambulatory blood pressure monitoring started 2 h before the study medication was given, and continued for at least 10 h after the medication.. The maximum drop in blood pressure appeared approximately 4 h after dose administration in both groups, and was more pronounced in the enalapril group. Patients in the enalapril group had a significantly higher incidence of asymptomatic hypotension. No symptomatic hypotension requiring a change in medication or a prolongation of hospitalisation was observed.. A low dose of perindopril is well-tolerated at initiation of ACE inhibitor therapy in patients with chronic heart failure and causes less first-dose hypotension than a low dose of enalapril.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Chronic Disease; Dose-Response Relationship, Drug; Enalapril; Female; Heart Failure; Humans; Hypotension; Incidence; Male; Middle Aged; Perindopril; Prospective Studies; Risk Factors; Single-Blind Method; Stroke Volume

Unlike angiotensin converting enzyme inhibitors (ACEI), few long-term studies have shown calcium antagonists to retard the progression of renal dysfunction. Our aim was to prospectively compare the effects of amlodipine and ACEI (enalapril) on renal function in hypertensive patients with renal impairment due to chronic glomerulonephritis and essential hypertension. A total of 72 hypertensive patients with serum creatinine (Cr) > 1.5 mg/dL were randomly allocated to treatment with either drug. During a 1-year period, 33% of the patients treated with ACEI dropped out due to adverse events, whereas 9% of patients with amlodipine dropped out. Data of 28 patients were available for analysis of more than 1-year follow-up. Reductions in blood pressure were comparable between the amlodipine (from 165/101 to 138/81 mm Hg) and ACEI groups. Serum Cr increased from 2.1+/-0.8 (SD) to 2.6+/-1.0 mg/dL with amlodipine (n = 16), but the difference was equivalent to that with ACEI (n = 12). Creatinine clearance (Ccr) in the moderate dysfunction group (basal Cr, 1.5 to 2.0 mg/dL) changed from 36+/-10 to 33+/-11 mL/min (not significant) with amlodipine, and the change was similar to that noted with ACEI. Annual declines in Ccr with amlodipine (-3.7 mL/min/year) and ACEI (-2.6 mL/min/year) were comparable, and both tended to be smaller than the annual decline in glomerular filtration rate reported in the Modification of Diet in Renal Disease study (-6 mL/min/year). Serum potassium was increased significantly (P < .01), from 4.5+/-0.4 to 5.3+/-0.8 mEq/L, only in the ACEI group. This 1-year prospective study demonstrated the effect of amlodipine on renal function to be likely the same as that of ACEI. Furthermore, amlodipine was better tolerated than ACEI for hypertensive patients with renal dysfunction.

Topics: Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Captopril; Chronic Disease; Enalapril; Female; Glomerulonephritis; Humans; Hypertension; Kidney; Male; Middle Aged; Prospective Studies; Time Factors

Chronic cor pulmonale (CPC) in patients with chronic obstructive pulmonary disease (COPD) is a predictor of mortality. ACE inhibitors (ACEIs) improve the symptoms and reduce mortality of left ventricular or congestive failure, however their long term use in patients with CPC has not been tested. The aim of this study is to assess the effect on exercise tolerance and cardiorespiratory function of long term administration of enalapril in patients with CPC.. Placebo-controlled, double blind, randomized study. 28 patients (24 men and 4 women, mean age of 68.11 +/- 7.78, range 51-79) with CPC and without exacerbation of their respiratory symptoms at baseline were double blind randomised to receive enalapril or placebo for 6 months, added to their previous therapy. Respiratory function test, exercise tolerance ("six minutes walking test") and isotopic ventriculography were performed at baseline and at the end of the study.. At baseline there were no differences in FEV1, FVC, FEV1/FVC and exercise tolerance. Both placebo and enalapril were well tolerated. At the end of the study, patients taking enalapril increased their exercise tolerance an 8.9% (19 m) vs 4.7% (33 m) in the placebo group (p 0.44; 95 percent confidence interval, -41.10 to 91.99). RVEF improved a 6.4% with enalapril but worsened a 7.09% in placebo group (p 0.15; 95 percent confidence interval, -12.87 to 2.10).. Long term administration of enalapril do not improve neither exercise tolerance, nor right ventricular (RV) function, although given in increasingly doses is well tolerated and might prevent further worsening in RV systolic function.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Double-Blind Method; Enalapril; Exercise Tolerance; Female; Humans; Male; Middle Aged; Pulmonary Heart Disease; Spain; Time Factors; Ventricular Function, Right

We examined the effect of long-term treatment with two doses of the angiotensin converting enzyme (ACE) inhibitor enalapril on various immunological variables in patients with chronic congestive heart failure (CHF).. Immunological mediators are increasingly recognized to play a pathogenic role in the pathophysiology of CHF. Whether ACE inhibitor therapy modifies immunological variables has not previously been investigated.. Seventy-five patients (mean age 52 +/- 11 years) with CHF were randomized between low-(5 m g daily) and high-dose (40 mg daily) enalapril in a double-blind trial. Circulating levels of immunological parameters (i.e., proinflammatory cytokines, chemokines and adhesion molecules) were measured at baseline, at 10 weeks and at the end of the study (34 weeks).. All immunological parameters, except soluble interleukin (IL)-6 receptor, were increased in CHF compared with 21 healthy controls. During the study immunoreactive IL-6 levels decreased (p < 0.05) and soluble IL-6 receptor increased (p < 0.05) during high-dose but not during low-dose enalapril therapy. Furthermore, IL-6 bioactivity decreased only during the high-dose (p < 0.001), resulting in a significant difference in change during treatment between the two dosage groups (p < 0.001). This decrease in IL-6 bioactivity was significantly associated with decreased interventricular septum thickness as assessed by echocardiography (r = 0.56, p = 0.013). No other variables changed during treatment.. In patients with severe CHF, high-dose enalapril therapy is associated with a significant decrease in IL-6 activity. However, despite treatment with a high-dose ACE inhibitor, a persistent immune activation exists in these patients which may be of importance for the progression of CHF.

Topics: Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Chemokine CCL2; Chronic Disease; Cytokines; Double-Blind Method; Echocardiography; Enalapril; Female; Heart Failure; Heart Septum; Humans; Hypertrophy, Left Ventricular; Immunoenzyme Techniques; Interleukin-1; Interleukin-6; Male; Methotrexate; Middle Aged; Neopterin; P-Selectin; Receptors, Interleukin-6; Treatment Outcome; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

The aim of our investigation was assessment of enalapril effects in cor pulmonale. 20 patients with chronic obstructive pulmonary diseases complicate with cor pulmonale received combined treatment including enalapril. The course of such treatment led to a significant lowering of systolic and diastolic pressure in the pulmonary artery, systemic arterial pressure, specific peripheral resistance and minute volume in patients with hyperkinetic and mixed types of hemodynamics. Parameters of ECG and exercise tolerance improved. Enalapril is effective in correction of pulmonary and central hemocirculation in chronic cor pulmonale.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Enalapril; Female; Humans; Male; Middle Aged; Pulmonary Heart Disease

A six month long double-blind, placebo-controlled, crossover design pharmacological study was conducted on 14 chronically psychotic, institutionalized patients who suffered from chronic water abuse ("psychogenic polydipsia"). Effects of clonidine and enalapril administered separately and individually were assessed for possible beneficial effects on both physiological parameters such as diurnal weight gain, urine output, and serum sodium levels and on signs of delirium as measured by neurobehavioral testing. Improvement, particularly in tests reflecting fluid consumption, was found with either or both drugs in approximately 60% of test subjects, although no behavioral improvement was demonstrated. As a result of evidence for delayed and carry-over effects the authors recommend that future studies employ phases longer than one month and/or include washout periods.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antipsychotic Agents; Chronic Disease; Clonidine; Cross-Over Studies; Double-Blind Method; Drinking Behavior; Drug Therapy, Combination; Enalapril; Female; Humans; Male; Middle Aged; Schizophrenia; Schizophrenic Psychology

To investigate the efficacy and safety of fosinopril in the treatment of chronic heart failure (CHF), patients with mild to moderate CHF and left ventricular ejection fractions <40% were randomly assigned in a double-blind manner to receive fosinopril 5 to 20 mg every day (n = 122) or enalapril 5 to 20 mg every day (n = 132) for 1 year.. The event-free survival time was longer (1.6 vs 1.0 months, P= .032) and the total rate of hospitalizations plus deaths was smaller with fosinopril than with enalapril (19.7% vs 25.0%, P= .028). There was consistently better symptom improvement with fosinopril (P< .05). The incidence of orthostatic hypotension was lower in the fosinopril group (1.6% vs 7.6%, P< .05).. Fosinopril 5 to 20 mg every day was more effective in improving symptoms and delaying events related to worsening of CHF and produced less orthostatic hypotension than enalapril 5 to 20 mg every day.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Disease-Free Survival; Dose-Response Relationship, Drug; Double-Blind Method; Enalapril; Female; Fosinopril; France; Heart Failure; Humans; Male; Middle Aged; Treatment Outcome

To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62 +/- 11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n = 7), hypertension (n = 2), and atrial fibrillation (n = 1). Radioiodinated metaiodobenzyl guanidine (123I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, (1) left ventricular ejection fraction (LVEF) increased significantly from 38.3 +/- 6.9% to 47.5 +/- 14.7%; (2) sub-maximal exercise time increased significantly from 205 +/- 112 to 272 +/- 120 seconds; (3) the heart to mediastinum (H/M) ratio of 123I-MIBG increased significantly (early image: 1.99 +/- 0.38 versus 2.20 +/- 0.50; delayed image: 1.86 +/- 0.44 versus 2.09 +/- 0.51); and (4) the washout rate of 123I-MIBG decreased slightly from 29.1 +/- 9.1% to 25.4 +/- 7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and 123I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure.

Topics: 3-Iodobenzylguanidine; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Fibrillation; Chronic Disease; Enalapril; Female; Heart Failure; Humans; Hypertension; Iodine Radioisotopes; Male; Middle Aged; Myocardial Infarction; Radionuclide Imaging; Radiopharmaceuticals; Stroke Volume; Ventricular Function, Left

The therapeutic benefit of an angiotensin-converting enzyme (ACE) inhibitor in combination with a different type of vasodilator is unknown.. To evaluate the effects of a combined therapy on quality of life, exercise tolerance, and hemodynamic parameters, patients with severe heart failure (New York Heart Association classes III and IV, ejection fraction below 35%) who were on ACE inhibitor therapy were randomly assigned to additional double-blind treatment with urapidil (60-120 mg/d) or placebo for 12 weeks. After enrollment of 36 patients, the study was terminated early because no beneficial effects on exercise tolerance and hemodynamic parameters could be shown for the urapidil treatment, and a trend toward increased mortality of the urapidil group was observed (odds ratio, 4.92 [0.49-49.6]; P = .167).. The combination of urapidil with an ACE inhibitor in the treatment of severe chronic congestive heart failure does not seem to offer any advantages over therapy with an ACE inhibitor alone and may have potentially harmful effects.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Enalapril; Exercise Tolerance; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Odds Ratio; Oxygen Consumption; Piperazines; Quality of Life; Survival Analysis; Vasodilation; Vasodilator Agents

Therapy with angiotensin-converting enzyme inhibitors and nonselective vasodilators (hydralazine and isosorbide dinitrate) has become accepted treatment in patients with symptomatic, chronic congestive heart failure (CHF), and has been demonstrated in large clinical trials to ameliorate symptoms, improve exercise performance, and reduce cardiac mortality. Nevertheless, the management of patients with CHF remains a therapeutic challenge. The second Vasodilator-Heart Failure Trial (V-HeFT II) showed that the average 2-year mortality with enalapril (18%) was significantly lower than that with hydralazine-isosorbide dinitrate (25%) but, somewhat surprisingly, the nonspecific vasodilators produced significantly more improvement in exercise performance and left ventricular function. Such data suggest that improvement in symptoms, hemodynamics, and survival may not be afforded by the use of a single class of vasodilator therapy, but might be optimized by the combined use of different agents. This report describes the rationale and design of V-HeFT III, a multicenter, prospective, randomized, double-blind, placebo-controlled trial comparing the effects of chronic oral extended-release felodipine (felodipine ER) 2.5 to 5 mg twice daily, when added to a stable regimen of enalapril and loop diuretics, with or without digoxin, on exercise performance, morbidity, and mortality in patients with New York Heart Association functional class II to III CHF followed for a minimum of 12 weeks. Felodipine is a second-generation dihydropyridine calcium antagonist with a high degree of vascular selectivity which, in the doses used in this study, exerts its systemic arterial effect by decreasing peripheral vascular resistance without producing negative inotropic effects. The results of V-HeFT III may shed important light on the role of additive vasodilator therapy in the management of patients with CHF.

Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiotonic Agents; Chronic Disease; Digoxin; Diuretics; Double-Blind Method; Drug Therapy, Combination; Enalapril; Exercise Test; Felodipine; Heart Failure; Hemodynamics; Humans; Prospective Studies; Quality of Life; Research Design; Treatment Outcome; Vasodilator Agents

Although post exercise proteinuria has long been known, its exact pathophysiology is unclear. Our objective was to determine whether long-term angiotensin converting enzyme (ACE) inhibition by different ACE inhibitors had an influence on post exercise proteinuria. We studied 14 patients who also had mild, chronic proteinuria caused by diabetes mellitus or chronic glomerulonephritis. We compared changes both in chronic (baseline) and post exercise proteinuria, during and after treatment with three different ACE inhibitors, with appropriate washout periods for the three drugs to all 14 patients. Proteinuria (mg/24 hours +/- SD), prior to the treatment was 682 +/- 92. Proteinuria after treatment for 30 days with benazepril was 464.4 +/- 82.6 (p < 0.001), with enalapril: 477.1 +/- 105.5 (p < 0.001), and captopril: 504.7 +/- 100.1 (p < 0.001). Proteinuria three days after discontinuing the treatment with benazepril was 532.4 +/- 113.5, (p < 0.01), with enalapril: 561.3 +/- 128.5, (p < 0.01), and with captopril: 620.8 +/- 101.8, p = n.s. Post exercise proteinuria prior to treatment (mg/min. +/- SD) was: 1.38 +/- 0.32, vs. after a 30-day treatment period with benazepril: 0.81 +/- 0.19 (p < 0.001), enalapril: 0.95 +/- 0.24, (p < 0.001), captopril: 1.09 +/- 0.27 (p < 0.02). Post exercise proteinuria three days after discontinuing the treatment was (blood pressure already back to baseline): in case of benazepril: 1.26 +/- 0.36 (p = n.s.), of enalapril: 1.17 +/- 0.46 (p = n.s.), and of captopril: 1.34 +/- 0.41 (p = n.s.). We conclude that the renin-angiotensin system plays a significant role in the pathogenesis of post exercise proteinuria; the antiproteinuric effect of ACE inhibition in exercise-induced proteinuria seems to be associated chiefly with the hemodynamic changes due to these drugs, whereas in chronic proteinuria the antiproteinuric and antihypertensive effects are, at least partially, dissociated.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Captopril; Chronic Disease; Diabetes Mellitus, Type 2; Enalapril; Exercise; Female; Glomerulonephritis; Humans; Male; Proteinuria

Topics: Adult; Altitude Sickness; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Enalapril; Female; Hematocrit; Humans; Male; Middle Aged; Treatment Outcome

This study assessed the feasibility of an efficacy trial comparing angiotensin-converting enzyme inhibition and angiotensin II receptor antagonism in heart failure. Patients with moderate or severe heart failure whose condition had previously been stabilized by treatment with a converting enzyme inhibitor were randomly assigned to receive enalapril or losartan. The study was designed to detect any signs of clinical deterioration during double-blind treatment.. Losartan is a specific, nonpeptide angiotensin II receptor-1 antagonist with a vasodilator hemodynamic profile similar to that of converting enzyme inhibitors. Although therapy with specific receptor blockade has certain theoretic advantages over nonspecific converting enzyme inhibition, demonstration of a comparable therapeutic effect in patients with congestive heart failure will require a major effort comparing two active agents.. One hundred sixty-six patients with stable heart failure in New York Heart Association functional class III or IV and an ejection fraction < or = 35% were included in a multicenter, double-blind, parallel, enalapril-controlled trial. After a 3-week stabilization period with optimal therapy, including digitalis, diuretic drugs and a converting enzyme inhibitor, patients were randomly assigned to 8 weeks of therapy with losartan, 25 mg/day (n = 52); losartan, 50 mg/day (n = 56); or enalapril, 20 mg/day (n = 58). Patients were assessed with frequent clinical and laboratory evaluation and exercise testing.. No significant differences between groups in terms of changes in exercise capacity (6-min walk test), clinical status (dyspnea-fatigue index), neurohumoral activation (norepinephrine, N-terminal atrial natriuretic factor), laboratory evaluation or incidence of adverse experience were observed.. The results suggest that losartan and enalapril are of comparable efficacy and tolerability in the short-term treatment of moderate or severe congestive heart failure. A trial designed to compare the efficacy, tolerability and effect on mortality of long-term angiotensin II receptor blockade with converting enzyme inhibition is both feasible and ethically responsible.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Biphenyl Compounds; Chronic Disease; Confounding Factors, Epidemiologic; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Enalapril; Exercise Test; Feasibility Studies; Female; Heart Failure; Humans; Imidazoles; Losartan; Male; Middle Aged; Severity of Illness Index; Tetrazoles; Treatment Outcome

Topics: Adolescent; Chronic Disease; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Enalapril; Glycated Hemoglobin; Humans; Hypertension; Kidney

This study attempted to evaluate the long-term efficacy of enalapril versus hydralazine therapy on left ventricular volume, mass and function as well as on the renin-angiotensin system in chronic asymptomatic aortic regurgitation.. We tested the hypothesis that early administration of a vasodilator drug might be able to reduce left ventricular dilation and mass expansion. Because the renin-angiotensin system may be activated in chronic aortic regurgitation, early enalapril therapy might be beneficial.. Between 1990 and 1993, 76 asymptomatic nonrheumatic patients with mild to severe chronic aortic regurgitation were enrolled in a randomized, double-blind trial comparing enalapril with hydralazine. All patients underwent serial noninvasive studies. Seventy patients completed the 12-month follow-up.. At 1 year, patients receiving enalapril had a significant reduction in left ventricular end-diastolic and end-systolic volume indexes (124 +/- 15 vs. 108 +/- 17 ml/m2, p < 0.01; 50 +/- 12 vs. 40 +/- 14 ml/m2, p < 0.01, respectively) and mass index (131 +/- 16 vs. 113 +/- 19 g/m2, p < 0.01), whereas hydralazine therapy showed no significant changes. Both regimens not only had a significant reduction in left ventricular mean wall stress but also had a mild increase in exercise duration. Only enalapril therapy achieved a significant inhibition of the renin-angiotensin system, in contrast to hydralazine therapy. Moreover, the multiple r2 value from the analysis for end-diastolic volume index using the two variables of age and treatment drugs was 72.1% (p < 0.01).. Both regimens decrease left ventricular mean wall stress. Enalapril therapy achieves significant left ventricular mass regression, left ventricular end-diastolic and end-systolic volume index reduction and renin-angiotensin system suppression. These findings suggest that early unloading enalapril therapy has the potential to favorably influence the natural history of chronic aortic regurgitation.

Topics: Aged; Aortic Valve Insufficiency; Chronic Disease; Double-Blind Method; Echocardiography; Enalapril; Female; Follow-Up Studies; Hemodynamics; Humans; Hydralazine; Male; Middle Aged; Renin-Angiotensin System; Vasodilator Agents; Ventricular Function, Left

It has not been determined previously whether patients with severe chronic congestive heart failure differ in demographic characteristics with respect to left ventricular systolic dysfunction (LVD). In patients with severe chronic congestive heart failure in NYHA IV, an optional protocol in the CONSENSUS-I trial was designed to ascertain whether there were any differences in patient characteristics regarding the degree of LVD defined as left ventricular fractional shortening (FS). A subgroup of 54 patients from the CONSENSUS-I trial were evaluated with M-mode echocardiography. Patients with FS above median (14%) were older (74 +/- 7 vs. 68 +/- 7, p < 0.01), more often female (48 vs. 15%, p < 0.05) and had lower heart rates (77 +/- 15 vs. 95 +/- 17, p < 0.01). Analysis of the 2-year follow-up from the end of the trial was also performed. In the placebo group, patients with FS > 14% had significantly better prognosis than patients with FS < 14%. In the enalapril-treated group no such difference in survival was seen. The difference between the original treatment groups remained, despite the fact that treatment with enalapril was then made available to all surviving patients. In conclusion, patients with advanced chronic congestive heart failure and less severe LVD have different demographic characteristics than patients with more severe LVD. In the placebo group, but not in the enalapril group, prognosis was better in patients with less severe LVD.

Topics: Aged; Chronic Disease; Echocardiography; Enalapril; Female; Heart Failure; Humans; Male; Systole; Ventricular Dysfunction, Left; Ventricular Function, Left

We evaluated the effect of enalapril on proteinuria in 20 patients with chronic glomerulonephritis (CGN) and renal insufficiency. Patients were accepted into the study according to the following criteria: 1) a serum creatinine (s-Cr) level over 1.5 mg/dl or a creatinine clearance (Ccr) under 70 ml/min; and 2) urinary protein (UP) over 1.0 g/day, expect for the cases with uncontrollable hypertension. We measured total protein (TP), albumin, s-Cr, Ccr, UP, and Ht during the elanapril therapy. After enalapril therapy, UP slowly decreased, and TP and albumin levels increased. The levels of s-Cr and Ccr did not vary. None of the patients required discontinuation of enalapril therapy caused by side effects, such as anemia or hyperkalemia. In conclusion, enalapril has the effect of decreasing in proteinuria and increasing TP and albumin in patients with CGN and renal insufficiency irrespective of the original diseases.

Topics: Adolescent; Adult; Aged; Chronic Disease; Enalapril; Female; Glomerulonephritis; Humans; Male; Middle Aged; Proteinuria; Renal Insufficiency

The pharmacokinetics and haemodynamic effects of orally administered spirapril, a novel angiotensin-converting enzyme (ACE) inhibitor, have been investigated in patients with liver cirrhosis (n = 10), in patients with chronic, non-cirrhotic liver disease (n = 8) and in a control group of healthy subjects (n = 16). The absorption and elimination of spirapril did not differ between patients with liver disease and control subjects. In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 micrograms.h.l-1, 923 micrograms.h.l-1 and 1300 micrograms.h.l-1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively. Compared to healthy subjects, cirrhotic patients had a reduced rate constant of spiraprilat formation (1.10 h-1 in patients vs. 2.00 h-1 in control subjects) while the elimination half-life of spiraprilat was not different. The effect of spirapril on diastolic blood pressure was decreased in patients with chronic liver disease as compared to the controls. Thus, the pharmacokinetics of spirapril was unchanged in patients with different types of liver disease, including cirrhosis. However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients.

Topics: Administration, Oral; Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Chronic Disease; Enalapril; Female; Glycogen Storage Disease; Half-Life; Hemodynamics; Humans; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Diseases; Male; Middle Aged; Pulse

We have previously corroborated that lymphocyte beta-adrenergic receptor density is significantly reduced in patients with chronic heart failure. It is well known that angiotensin converting enzyme inhibitors normalize the function of sympathetic nervous system. We have assessed the effect of enalapril on lymphocyte beta-adrenergic receptor system from patients with chronic heart failure (n = 14) using a random, cross and double blind protocol. Our results show that the improvement in clinical score and ventricular function were not related with changes in the number and affinity of beta-adrenergic receptor nor cyclic AMP content in lymphocytes obtained from these patients.

Topics: Adult; Analysis of Variance; Chronic Disease; Cyclic AMP; Double-Blind Method; Enalapril; Female; Heart Failure; Humans; Lymphocytes; Male; Middle Aged; Receptors, Adrenergic, beta

This study was undertaken to determine if a standard dose of aspirin interacts relevantly with the circulatory effects of enalapril in severe heart failure.. The frequent association of heart failure with coronary artery disease confers potential for combined treatment with an angiotensin-converting enzyme inhibitor and the prostaglandin synthesis inhibitor aspirin, the pharmacodynamic actions of which are, in part, mutually opposed.. In 18 patients, on 3 consecutive days, hemodynamic measurements were performed at baseline and 4 h after administration of a double placebo, enalapril (10 mg) plus placebo and enalapril plus aspirin (350 mg) according to a double-blind, randomized, crossover protocol.. Enalapril given before aspirin led to significant decreases in systemic vascular resistance, left ventricular filling pressure and total pulmonary resistance together with a significant increase in cardiac output. When given with or on the day after aspirin, enalapril did not elicit significant changes in any of these variables. There was a clear tendency to lower values for pulmonary artery pressure on all regimens, and slowing of the heart rate was incurred whether or not aspirin had been given. Chi-square analysis of the individual responses showed that the probability of effecting a decrease in systemic vascular resistance > or = 300 dynes.s.cm-5 was six times greater when enalapril was given without aspirin (p < 0.01).. In severe heart failure, the prostaglandin synthesis inhibition by aspirin counteracts the systemic arterial vasodilation of angiotensin-converting enzyme inhibition with enalapril and substantiates its dependence on the integrity of prostaglandin metabolism. Trends toward reductions of pulmonary artery pressure and slowing of the heart rate were still observed, presumably subsequent to lowered norepinephrine concentrations indicating maintenance of prostaglandin-independent actions of angiotensin-converting enzyme inhibition.

Topics: Adult; Aged; Aspirin; Chi-Square Distribution; Chronic Disease; Coronary Disease; Double-Blind Method; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Pulmonary Circulation; Pulmonary Wedge Pressure; Renin; Severity of Illness Index; Vascular Resistance

The effects of flosequinan and enalapril on exercise capacity (bicycle exercise duration), quality-of-life symptomatology (visual analogue scales) and New York Heart Association (NYHA) grading, were compared in 61 patients with chronic heart failure (NYHA, grade III). Bicycle exercise duration improved similarly with flosequinan (+27%) and enalapril (+18%); in patients completing the study, flosequinan produced a significantly greater increase in exercise time at week 12, compared with enalapril (P = 0.02). Improvements in visual analogue scores relating to general health, energy and vitality, ability to perform physical activities and breathing performance, were equivalent for both drugs. Changes in NYHA classification showed that 27 (55%) of 49 patients completing the study had improved by at least one NYHA grade (15 (68%) patients on flosequinan; 12 (44%) on enalapril). The overall safety and tolerability of the two treatments was similar; 18 patients reported adverse effects while on flosequinan, compared with 19 patients on enalapril. Neither treatment was associated with any clinically important changes in haematological or biochemical variables, although some treatment-related effects were observed. This study confirms that flosequinan achieved similar efficacy to enalapril in the symptomatic relief of chronic heart failure. The effect of flosequinan on survival in chronic heart failure has not been tested; pending such studies, our data suggest that it may prove a useful alternative therapy in patients where ACE inhibitors are contraindicated or poorly tolerated.

Topics: Adult; Aged; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Enalapril; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Pain Measurement; Quinolines; Vasodilator Agents

To compare the first dose responses to low dose angiotensin converting enzyme inhibitors (captopril, enalapril, and perindopril) in elderly patients with stable chronic heart failure.. Double blind, randomised, placebo controlled, parallel, group prospective study of elderly patients with stable chronic heart failure.. General hospital in-patient admissions for supervised diuretic withdrawal (24-48 hours) and the introduction of angiotensin converting enzyme inhibitor therapy.. 48 unselected elderly (58-85 years) patients with symptomatic but stable chronic heart failure (New York Heart Association grades II-IV) confirmed by clinical history, examination, and cardiological investigations. Patients gave their written and informed consent to receive their initial treatment under double blind conditions; blood pressure was monitored and blood samples taken to measure the pharmacokinetic and neurohormonal responses.. Patients were randomised to receive a daily oral dose of placebo, captopril (6.25 mg), enalapril (2.5 mg), or perindopril (2 mg).. Blood pressure and heart rate responses, drug concentration, and plasma renin and ACE activities. Differences between treatment groups were analysed by analysis of variance.. The four randomised groups of patients had similar age, severity of heart failure (NYHA class), pretreatment diuretic dosage, plasma renin activity, and serum electrolyte state. Placebo treatment caused a modest but significant diurnal fall in blood pressure. Captopril produced a significant early (1.5 hours) and brief fall in blood pressure. The blood pressure fall with enalapril was later (4-10 hours), longer lasting, and was associated with significant slowing of supine heart rate. Though perindopril produced a similar plasma ACE inhibition to that produced by enalapril, it only caused changes in blood pressure that were similar to those caused by placebo.. This controlled study is the first to indicate a qualitative difference in the acute response to angiotensin converting enzyme inhibitors with similar structure and metabolism (that is, enalapril and perindopril). Low dose perindopril seems to be less likely to cause hypotension in patients with heart failure. The explanation for the differences is unclear but may reflect differential effects on local tissue angiotensin generation.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Captopril; Chronic Disease; Double-Blind Method; Enalapril; Female; Heart Failure; Heart Rate; Humans; Indoles; Male; Middle Aged; Peptidyl-Dipeptidase A; Perindopril; Renin

The aim of this study was to investigate the role of the renin-angiotensin-aldosterone system during anti-heart failure treatment with additional enalapril versus conventional vasodilator therapy (hydralazine + sorbitrate) and to assess whether or not enalapril can be suggested as the preferential vasodilator therapy in patients with chronic congestive heart failure. Over a 2.5-year period, 120 patients (New York Heart Association II-IV, creatinine less than or equal to 2.0 mg/dl) were enrolled in the study and randomly assigned to receive enalapril or hydralazine and sorbitrate therapy in addition to optimal digitalis and diuretics administration. At the end of a one-year followup, there was a tendency for mortality to be lower in the enalapril[correction of enlapril] group (4 cases) compared to the conventional group (9 cases), but the difference was not significant (p = 0.21). Both groups showed similar increases in plasma renin activity. The plasma aldosterone level decreased significantly in the enalapril group (p less than 0.005); whereas it rose significantly in the conventional group (p less than 0.005). The plasma norepinephrine level of the enalapril group fell significantly when compared with the conventional group. Thus, enalapril therapy achieved better reduction in the activating sympathetic system (p less than 0.0001). Reduction in the anti-diuretic hormone level was also found to be highly significant in the enalapril group, whereas no difference was seen in the conventional group. Furthermore, the serum creatinine level and blood urea nitrogen remained unchanged in the conventional group; whereas both were demonstrated to be reduced significantly in the enalapril group at a 1-year follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Chronic Disease; Enalapril; Heart Failure; Humans; Male; Middle Aged; Renin-Angiotensin System; Vasodilator Agents

Arterial hypertension and proteinuric nephropathy are common features in diabetic patients. In streptozotocin-diabetic rats, it has been possible to reduce the blood pressure and proteinuria by converting enzyme inhibitors, and so slowing the decline of kidney function. These results have been confirmed in diabetic patients affected by arterial hypertension and persistent proteinuria. However, up to now it has not been clear if these favorable renal effects are related specifically to converting enzyme inhibition. In the attempt to clarify this last point, from a practical as well as from a speculative point of view, 12 type 2 diabetic outpatients affected by mild to moderate arterial hypertension and persistent macroalbuminuria (greater than 250 mg/daily, at least on three consecutive occasions) without any other signs of renal diseases were studied. In a randomized sequence and in a double blind fashion, after a washout period of 3 weeks, the patients underwent pharmacological treatment which consisted of enalapril 20 mg o.d., chlorthalidone 12.5 mg o.d., atenolol 50 mg o.d. and placebo o.d. Each treatment lasted 45 days. Kidney function, blood pressure and heart rate were checked at the beginning and at the end of each treatment, while urinary albumin excretion was measured at the end of the 4th, 5th, and 6th week of each treatment. Blood pressure significantly decreased in a similar fashion after each active treatment, while kidney function did not change significantly. Urinary albumin excretion rate significantly decreased after enalapril and atenolol, but did not change after chlorthalidone. According to these results we can hypothesize that the inhibition of tissue angiotensin formation and its related change on the glomerular permeability, rather than renal and systemic hemodynamic features, seem to be the common mechanisms by which both enalapril as well as atenolol decrease the albuminuria in our patients.

Topics: Atenolol; Blood Pressure; Chlorthalidone; Chronic Disease; Diabetic Nephropathies; Diabetic Retinopathy; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Kidney; Male; Middle Aged; Proteinuria

Patients with congestive heart failure have a high mortality rate and are also hospitalized frequently. We studied the effect of an angiotensin-converting-enzyme inhibitor, enalapril, on mortality and hospitalization in patients with chronic heart failure and ejection fractions less than or equal to 0.35.. Patients receiving conventional treatment for heart failure were randomly assigned to receive either placebo (n = 1284) or enalapril (n = 1285) at doses of 2.5 to 20 mg per day in a double-bind trial. Approximately 90 percent of the patients were in New York Heart Association functional classes II and III. The follow-up averaged 41.4 months.. There were 510 deaths in the placebo group (39.7 percent), as compared with 452 in the enalapril group (35.2 percent) (reduction in risk, 16 percent; 95 percent confidence interval, 5 to 26 percent; P = 0.0036). Although reductions in mortality were observed in several categories of cardiac deaths, the largest reduction occurred among the deaths attributed to progressive heart failure (251 in the placebo group vs. 209 in the enalapril group; reduction in risk, 22 percent; 95 percent confidence interval, 6 to 35 percent). There was little apparent effect of treatment on deaths classified as due to arrhythmia without pump failure. Fewer patients died or were hospitalized for worsening heart failure (736 in the placebo group and 613 in the enalapril group; risk reduction, 26 percent; 95 percent confidence interval, 18 to 34 percent; P less than 0.0001).. The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions.

Topics: Blood Pressure; Cause of Death; Chronic Disease; Double-Blind Method; Electrolytes; Enalapril; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Kidney; Male; Middle Aged; Patient Compliance; Stroke Volume; Survival Rate

To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial.. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group.. The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination.

Topics: Adolescent; Adult; Aged; Chronic Disease; Death, Sudden; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Enalapril; Heart Failure; Hospitalization; Humans; Hydralazine; Isosorbide Dinitrate; Male; Middle Aged; Norepinephrine; Oxygen Consumption; Patient Compliance; Physical Exertion; Stroke Volume; Survival Rate

Topics: Adult; Captopril; Chronic Disease; Clinical Trials as Topic; Enalapril; Humans; Male; Schizophrenia; Schizophrenic Psychology; Water Intoxication

A single blind, placebo controlled, dose-ranging 3 month study of the effects of enalapril on cardiovascular parameters, clinical status and self-paced exercise capacity was undertaken in 12 Nigerians with chronic heart failure. Enalapril exerted only a modest reduction in blood pressure and heart rate but significantly improved functional capacity (P less than 0.01), and prolonged self-paced exercise time (P less than 0.05) compared to the placebo baseline. The pressure rate product and the double product corrected for exercise time, an index of myocardial oxygen demand, exhibited a significant and sustained reduction on enalapril treatment (P less than 0.01). Concentration of sodium in the serum was significantly increased (P less than 0.05) but concentrations of potassium and creatinine were unaltered. These results demonstrate the sustained efficacy of enalapril in black Africans with heart failure and indicate no important racial difference in the response to inhibition of angiotensin converting enzyme in congestive heart failure.

Topics: Adult; Aged; Black People; Blood Pressure; Chronic Disease; Dose-Response Relationship, Drug; Enalapril; Female; Heart Failure; Heart Function Tests; Heart Rate; Humans; Male; Middle Aged; Nigeria; Physical Exertion; Single-Blind Method

A prospective, randomized efficacy study of low-dose enalapril was undertaken in 38 outpatients (24 men, 14 women; mean age 58 [41-69] years) with chronic heart failure (NYHA functional class III-IV). All patients were pretreated with digitalis and diuretics, some also with conventional vasodilators. 19 patients (group E) received in addition to their previous medication, 5 mg enalapril daily, while the other 19 (group K) continued with their previous therapy. Three months later, 15 patients in group E improved by at least one NYHA functional class and none died (P less than 0.02). Four patients in group K died and only one patient improved by one class. After three months, left ventricular ejection fraction was significantly higher (P less than 0.0001) in group E (39 +/- 19%) compared to group K (30 +/- 14%). In group E, plasma aldosterone concentration decreased significantly (P less than 0.0001) by 33.4 +/- 6.5 ng/dl, while in group K no significant change occurred (delta 1.1 +/- 1.2 ng/dl). Thus, low-dose enalapril in addition to conventional therapy may improve the clinical status of patients in severe chronic heart failure. This improvement is associated with an increase in left ventricular ejection fraction and reduction in secondary hyperaldosteronism.

Topics: Chi-Square Distribution; Chronic Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enalapril; Heart Failure; Humans; Prospective Studies; Randomized Controlled Trials as Topic; Stroke Volume; Time Factors

The effects of the angiotensin converting enzyme inhibitor enalapril on myocardial sympathetic tone, as represented by noradrenaline overflow, were studied in 14 men with congestive heart failure (mean ejection fraction 20%) in a double blind crossover comparison with placebo. Arterial and coronary sinus catecholamine concentrations and oxygen content, and coronary sinus blood flow, were measured at rest and during peak symptom limited upright exercise on a bicycle ergometer. There were no significant changes four hours after the first dose of enalapril, but after six weeks of treatment (10-20 mg/day) enalapril reduced myocardial overflow of noradrenaline at peak exercise. The external workload (exercise duration) increased from baseline values after both placebo and enalapril, and there was no difference between placebo and enalapril at six weeks. Heart work, however, was lower after enalapril: stroke work index was reduced at rest and the double product was lower at peak exercise. The reduction in maximal myocardial oxygen consumption after enalapril did not reach statistical significance. Coronary sinus adrenaline concentrations after enalapril and after placebo were not significantly different. The long term reduction of myocardial sympathetic activity on exercise may represent a significant benefit from angiotensin converting enzyme inhibition in heart failure and may reflect a reduced cardiac workload.

Topics: Adult; Aged; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Enalapril; Heart; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardium; Norepinephrine; Physical Exertion; Random Allocation; Sympathetic Nervous System

Benazepril hydrochloride is a nonsulfhydryl, long-acting angiotensin-converting enzyme inhibitor that is orally effective. This study was designed to determine the acute hemodynamic effects of this agent in patients with chronic congestive heart failure. Twenty-six patients with New York Heart Association class III or IV congestive heart failure and left ventricular ejection fractions less than 35%, cardiac indexes less than 2.1 L/min/m2, and pulmonary artery wedge pressures greater than 12 mm Hg were given 2 or 5 mg benazepril hydrochloride. All does produced significant (p less than 0.05) increases in cardiac output (26.7% to 31.6% above control) and heart rate (5.4% to 11.2% above control) and decreases in systemic (27.1% to 32.0% below control) and pulmonary (34.8% to 55.5% below control) vascular resistances, mean pulmonary (25.3% to 30.3% below control) and systemic (13.4% to 18.5% below control) arterial pressures, and pulmonary artery wedge pressure (46.9% to 51.1% below control). Twenty-four hours after an initial dose, systemic vascular resistance and pulmonary artery wedge pressures remained below control levels. Angiotensin-converting enzyme activity fell by 67.8% +/- 6.4%, with a 15.8% +/- 7.6% decline in aldosterone levels. Thus benazepril hydrochloride is an effective angiotensin-converting enzyme inhibitor that produces hemodynamic effects that persist for 24 hours after a single oral dose.

Topics: Adult; Aged; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Captopril; Chronic Disease; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Multicenter Studies as Topic; Peptidyl-Dipeptidase A; Renin; Time Factors

The effect of angiotensin converting enzyme inhibition on myocardial ischaemia was studied in 12 normotensive patients with chronic stable angina and exercise induced ST segment depression. The study was randomised, double blind, placebo controlled, and crossover with treatment periods of two weeks. Enalapril was used to inhibit angiotensin converting enzyme. Assessment was by angina diaries and maximum symptom limited treadmill exercise tests. The results for the whole group showed a significant reduction in systolic blood pressure at rest and at peak exercise. Mean total exercise duration was 466 s (95% confidence interval 406 to 525) when the patients were taking placebo and 509 s (436 to 583) when they were taking enalapril. Four patients prolonged their total exercise time (mean 450 to mean 591 s) by more than 20%. Two patients, however, developed ischaemia earlier on exercise and reduced their total exercise duration (mean 490 to mean 390 s). Although angiotensin converting enzyme inhibition tended to reduce myocardial ischaemia in the group as a whole, some patients improved while others deteriorated. Thus the effects of enalapril are variable and this may have important implications when enalapril is used to treat heart failure in patients with underlying severe ischaemic heart disease.

Topics: Aged; Angina Pectoris; Chronic Disease; Coronary Circulation; Coronary Disease; Double-Blind Method; Enalapril; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Nitroglycerin; Random Allocation

In a 3-month prospective, single-blind, controlled trial, 38 patients in New York Heart Association functional class III-IV were assigned to group E (n = 19): enalapril 5 mg/day in addition to the previous therapy with digitalis and diuretics, or group C (n = 19): continuation of the previous therapy. In group E, 79% of the patients improved by at least one NYHA functional class after 3 months. In group C, the functional class did not change and four patients died. The echocardiographically determined end-diastolic diameter of the left ventricle decreased in group E from 72 +/- 8 mm to 63 +/- 6 mm (p less than 0.001), and the scintigraphically determined ejection fraction of the left ventricle increased from 33 +/- 18% to 40 +/- 19% (p less than 0.002). In contrast, no significant change was found in group C. Plasma-renin activity increased in group E from 8.2 +/- 1.8 ng/ml h to 29.7 +/- 14 ng/ml h (p less than 0.001), and plasma aldosterone decreased from 47.7 +/- 7.6 ng/dl to 19.9 +/- 4.8 ng/dl (p less than 0.01). In group C no significant change occurred. Comparing the actual changes (deltas) of the NYHA functional class (p less than 0.02), end-diastolic diameter and ejection fraction of the left ventricle, plasma-renin activity, and plasma aldosterone (p less than 0.0001), a significant difference between the two groups was found. Thus, low-dose enalapril resulted in a significant improvement of the NYHA functional class in patients with severe chronic heart failure, accompanied by an improvement in left ventricular function and a decrease in secondary aldosteronism.

Topics: Aged; Aldosterone; Chronic Disease; Electrocardiography; Enalapril; Heart Failure; Heart Function Tests; Heart Ventricles; Humans; Middle Aged; Renin; Single-Blind Method

The Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) was terminated prematurely when an independent Ethical Review Committee concluded, on the basis of interim analyses, that continuation would not be advisable on either ethical or scientific grounds. Among 124 patients treated with enalapril and 120 randomized to placebo, 6-month mortality rates were 27 and 48%, respectively. The 2 groups were found to be well balanced with regard to baseline clinical characteristics, and a consistent treatment effect was evident among subgroups. Furthermore, the difference favoring enalapril was found to have been present since the beginning of the study and was consistent over time. Based on these findings, the study was halted on December 14, 1986.

Topics: Chronic Disease; Enalapril; Ethics, Medical; Heart Failure; Humans; Methods; Scandinavian and Nordic Countries

Topics: Captopril; Chronic Disease; Clinical Trials as Topic; Enalapril; Evaluation Studies as Topic; Heart Failure; Humans; Multicenter Studies as Topic; Placebos; Random Allocation

The acute hypotensive response to oral and parenteral enalapril (E) and lisinopril (LI) was assessed in 24 patients with chronic congestive heart failure in two open, randomized, balanced, crossover studies. In the E study, 12 patients received each of three treatments: a single oral dose of 10 mg E, a single intravenous bolus of 5 mg E, and a single intravenous bolus of 5 mg enalaprilat (ET). In the LI study, 12 patients received each of two treatments: a single oral dose of 10 mg LI and a single intravenous bolus of 5 mg LI. Intraarterial blood pressure was measured continuously. Significant decreases from baseline in mean arterial pressure (MAP) were observed in all cases, starting at 15 min. The maximal hypotensive effect (MAP; mean +/- SD) was greatest and the nadir earliest for intravenous ET (-30 +/- 7 mm Hg at 75 min) compared with oral E (-25 +/- 10 mm Hg at 210 min) and intravenous E (-19 +/- 10 mm Hg at 195 min). Oral E and intravenous E had similar onsets of action. The maximal reduction following oral LI (-19 +/- 13 mm Hg at 210 min) was similar to oral E and intravenous E. The effect of intravenous LI (-25 +/- 9 mm Hg at 105 min) was similar to that of intravenous ET. Among the parenteral treatments, E produced the most gradual and least pronounced reduction in blood pressure, and may be best suited for use in the acute situation to minimize the risk of abrupt hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Aged; Blood Pressure; Chronic Disease; Enalapril; Enalaprilat; Female; Heart Failure; Humans; Hypotension; Injections, Intravenous; Lisinopril; Male; Middle Aged

The efficacy of enalapril, a new angiotensin-converting enzyme inhibitor, was investigated in a double-blind placebo-controlled study in 24 patients with chronic heart failure. The patients belonging to NYHA functional class II-IV and treated with digoxin and diuretics were randomized to enalapril (12 patients) or placebo (12 patients) treatment for a 12-week period. Assessments were carried out at baseline and at 4 and 12 weeks during the treatment period. Complete data could be obtained on 10 patients receiving enalapril and on 11 patients receiving placebo. NYHA functional class improved by at least one class in 6 of 10 patients in the enalapril group, but only in 1 of 11 patients in the placebo group (chi 2 = 6.54; p less than 0.05). Duration of bicycle ergometer exercise increased significantly in the enalapril group from 8.8 +/- 3.4 to 11.3 +/- 4.2 (4 weeks) and to 11.2 +/- 3.6 min (12 weeks; p less than 0.05 for both), whereas it remained unchanged in the placebo group. Left ventricular ejection fraction by radionuclide ventriculography in the enalapril group increased significantly (baseline: 33.5 +/- 19.9%, 4 weeks: 40.0 +/- 20.0% (p less than 0.001), 12 weeks: 39.6 +/- 20.1% (p less than 0.01], whereas in the placebo group it did not change significantly from the baseline of 48.8 +/- 16.7%. The results indicate that enalapril induces a sustained relief of symptoms and improves exercise capacity in patients with heart failure. This subjective improvement appears to be accompanied by an increase in ejection fraction.

Topics: Adult; Aged; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged

To evaluate the concept that long duration of action is an advantageous property of angiotensin-converting enzyme inhibitors in the treatment of severe heart failure, we randomly assigned 42 patients to therapy with either a short-acting inhibitor (captopril, 150 mg daily) or a long-acting inhibitor (enalapril, 40 mg daily) for one to three months while concomitant therapy with digoxin and diuretics was kept constant. The treatment groups had similar hemodynamic and clinical characteristics at base-line evaluation and similar initial responses to converting-enzyme inhibition. During long-term therapy, captopril and enalapril produced similar decreases in systemic blood pressure, but the hypotensive effects of enalapril were more prolonged and persistent than those of captopril. Consequently, although the patients in both groups improved hemodynamically and clinically during the study, serious symptomatic hypotension (syncope and near syncope) was seen primarily among those treated with enalapril. Sustained hypotension also probably accounted for the decline in creatinine clearance (P less than 0.05) and the notable retention of potassium (P less than 0.05) observed in the patients treated with enalapril but not in those treated with captopril. We conclude that when large, fixed doses of converting-enzyme inhibitors are used in the treatment of patients with severe chronic heart failure, long-acting agents may produce prolonged hypotensive effects that may compromise cerebral and renal function, and thus they may have disadvantages in such cases, as compared with short-acting agents.

Topics: Adult; Aged; Blood Pressure; Captopril; Chronic Disease; Clinical Trials as Topic; Creatinine; Digoxin; Diuretics; Drug Therapy, Combination; Electrolytes; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Hypotension; Male; Middle Aged; Random Allocation

Hemodynamic effects of the new oral angiotensin-converting enzyme inhibitor, enalapril, were evaluated acutely in 15 patients with chronic heart failure and in 7 patients after 4 weeks of maintenance therapy. Initial hemodynamic effects were characterized by a significant increase in cardiac index (from 2.1 +/- 0.7 to 2.6 +/- 0.7 liters/min per m2) and a decrease in pulmonary capillary wedge pressure (from 30 +/- 6 to 24 +/- 7 mm Hg), right atrial pressure (from 14 +/- 5 to 11 +/- 4 mm Hg), mean arterial pressure (from 96 +/- 16 to 80 +/- 17 mm Hg) and systemic vascular resistance (from 1,820 +/- 480 to 1,200 +/- 410 dynes . s . cm-5) without any significant change in heart rate, pulmonary artery pressure and pulmonary vascular resistance. During maintenance therapy, the dose of diuretic drugs had to be increased because of systemic venous hypertension. Repeat hemodynamic study showed that after chronic therapy, cardiac index (2.1 +/- 0.7 vs. 3.0 +/- 0.08 liters/min per m2) and stroke volume index (24 +/- 10 vs. 36 +/- 7 ml/m2) remained elevated and pulmonary capillary wedge pressure was lower than control (30 +/- 6 vs. 16 +/- 6 mm Hg), indicating sustained improvement in left ventricular performance. Plasma renin activity increased and plasma norepinephrine levels decreased after enalapril therapy and these humoral changes persisted during maintenance therapy. All patients receiving chronic therapy had symptomatic improvement. Significant hypotension, which occurred in five patients at the initiation of therapy, appears to be the major side effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Clinical Trials as Topic; Dipeptides; Dose-Response Relationship, Drug; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Renin; Time Factors

To study whether the changes in bioequivalent drugs with different appearances are associated with an increase in lack of adherence and medication use errors, in patients >65years old treated with antihypertensive and lipid-lowering medications.. Observational longitudinal prospective cohort study with a one-year follow-up period between 1 January 2013 and 31 December 2014.. Primary Healthcare Centres in the Community of Madrid.. Patients ≥65years-old with a diagnosis of hypertension and/or dyslipidaemia receiving treatment with Enalapril and/or Amlodipine and/or Simvastatin.. Variables collected during a Primary Care consultation by means of a personal interview were: sociodemographic (age, gender, level of education), clinical variables, adherence (Morisky-Green test and direct counting), medication errors (number and type), medication changes and number, analytical (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides) and combined variable (error and/or adherence). There were 1 baseline and 4 quarterly visits.. The study included 274 patients with a mean age 72 (6.6) years, of whom 47.8% were female. Some medication changes were observed in 134 patients (48.9%), with a median of 3 (IQR 1-5) and a maximum of 11 changes. The risk of presenting with a medication use error or decreased adherence was increased in patients exposed to changes in all visits with RR 1.14 (1.16-1.69) at one year of follow-up. The most frequent error was the loss of dose. For each change in medication, the probability of a combined event increases by 41%.. The changes made in bioequivalent drugs with different appearance could increase the number of medication use errors and decrease the adherence. More studies should be carried out to assess how much this affects the control of the disease. The intervention section is not considered because it is an observational study.

Topics: Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Chronic Disease; Drug Labeling; Drug Packaging; Enalapril; Female; Follow-Up Studies; Humans; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Longitudinal Studies; Male; Medication Adherence; Medication Errors; Primary Health Care; Prospective Studies; Simvastatin

Myocardial infarction (MI) triggers a local inflammatory response which orchestrates cardiac repair and contributes to concurrent neuroinflammation. Angiotensin-converting enzyme (ACE) inhibitor therapy not only attenuates cardiac remodeling by interfering with the neurohumoral system, but also influences acute leukocyte mobilization from hematopoietic reservoirs. Here, we seek to dissect the anti-inflammatory and anti-remodeling contributions of ACE inhibitors to the benefit of heart and brain outcomes after MI.. C57BL/6 mice underwent permanent coronary artery ligation (n = 41) or sham surgery (n = 9). Subgroups received ACE inhibitor enalapril (20 mg/kg, oral) either early (anti-inflammatory strategy; 10 days treatment beginning 3 days prior to surgery; n = 9) or delayed (anti-remodeling; continuous from 7 days post-MI; n = 16), or no therapy (n = 16). Cardiac and neuroinflammation were serially investigated using whole-body macrophage- and microglia-targeted translocator protein (TSPO) PET at 3 days, 7 days, and 8 weeks. In vivo PET signal was validated by autoradiography and histopathology.. Myocardial infarction evoked higher TSPO signal in the infarct region at 3 days and 7 days compared with sham (p < 0.001), with concurrent elevation in brain TSPO signal (+ 18%, p = 0.005). At 8 weeks after MI, remote myocardium TSPO signal was increased, consistent with mitochondrial stress, and corresponding to recurrent neuroinflammation. Early enalapril treatment lowered the acute TSPO signal in the heart and brain by 55% (p < 0.001) and 14% (p = 0.045), respectively. The acute infarct signal predicted late functional outcome (r = 0.418, p = 0.038). Delayed enalapril treatment reduced chronic myocardial TSPO signal, consistent with alleviated mitochondrial stress. Early enalapril therapy tended to lower TSPO signal in the failing myocardium at 8 weeks after MI (p = 0.090) without an effect on chronic neuroinflammation.. Whole-body TSPO PET identifies myocardial macrophage infiltration and neuroinflammation after MI, and altered cardiomyocyte mitochondrial density in chronic heart failure. Improved chronic cardiac outcome by enalapril treatment derives partially from acute anti-inflammatory activity with complementary benefits in later stages. Whereas early ACE inhibitor therapy lowers acute neuroinflammation, chronic alleviation is not achieved by early or delayed ACE inhibitor therapy, suggesting a more complex mechanism underlying recurrent neuroinflammation in ischemic heart failure.

Topics: Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Animals; Chronic Disease; Enalapril; Heart; Inflammation; Mice; Mice, Inbred C57BL; Myocardial Infarction; Nervous System Diseases

Cough may be associated with complications such as syncope, urinary incontinence, pneumothorax, and less frequently, pulmonary hernia and costal fractures. Chronic cough is a cause of rib fractures and when they occur it is likely to affect more than one rib. We report a 53 year-old obese male in treatment with enalapril 10 mg for hypertension with a dry cough lasting five months. He consulted for bilateral chest pain and a Chest X ray examination showed symmetrical fractures in the seventh left and right ribs. Enalapril was discontinued, cough and pain subsided in two weeks.

Topics: Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Cough; Enalapril; Humans; Hypertension; Male; Middle Aged; Rib Fractures; Tomography, X-Ray Computed

In this article we have described clinical pharmacology and data of clinical studies of an innovational drug valsartan + sacubitril in patients with chronic heart failure (CHF). The use of supramolecular complex valsartan + sacubitril allows to elevate quality of life and improve prognosis of patients with CHF. High efficacy of valsartan+sacubitril relative to impact on composite primary end-point (cardiovascular death + hospitalization due to CHF) was demonstrated in the clinical trial PARADIGM-HF in which it was compared with angiotensin converting enzyme inhibitor enalapril. Advantages of the use of valsartan + sacubitril for the budget were demonstrated in pharmacoeconomic studies. These advantages are maximally realized at long-term administration. Cost-efficacy of the use of valsartan+sacubitril in pharmacotherapy of CHF is comparable with that of statins in the treatment of ischemic heart disease or implantation of a cardioverter-defibrillator in prevention of sudden cardiac death. Thus, introduction of the drug into practice can be expected to reduce budget expenditures.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Chronic Disease; Enalapril; Heart Failure; Humans; Quality of Life; Stroke Volume; Tetrazoles

To describe the adaptation of a global health economic model to determine whether treatment with the angiotensin receptor neprilysin inhibitor LCZ696 is cost effective compared with the angiotensin-converting enzyme inhibitor enalapril in adult patients with chronic heart failure with reduced left ventricular ejection fraction in the Netherlands; and to explore the effect of performing the cost-effectiveness analyses according to the new pharmacoeconomic Dutch guidelines (updated during the submission process of LCZ696), which require a value-of-information analysis and the inclusion of indirect medical costs of life-years gained.. We adapted a UK model to reflect the societal perspective in the Netherlands by including travel expenses, productivity loss, informal care costs, and indirect medical costs during the life-years gained and performed a preliminary value-of-information analysis.. The incremental cost-effectiveness ratio obtained was €17,600 per quality-adjusted life-year (QALY) gained. This was robust to changes in most structural assumptions and across different subgroups of patients. Probability sensitivity analysis results showed that the probability that LCZ696 is cost-effective at a €50,000 per QALY threshold is 99.8%, with a population expected value of perfect information of €297,128. On including indirect medical costs of life-years gained, the incremental cost-effectiveness ratio was €26,491 per QALY gained, and LCZ696 was 99.46% cost effective at €50,000 per QALY, with a population expected value of perfect information of €2,849,647.. LCZ696 is cost effective compared with enalapril under the former and current Dutch guidelines. However, the (monetary) consequences of making a wrong decision were considerably different in both scenarios.

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Chronic Disease; Cost-Benefit Analysis; Drug Combinations; Economics, Pharmaceutical; Enalapril; Female; Guidelines as Topic; Heart Failure; Humans; Male; Middle Aged; Models, Economic; Neprilysin; Netherlands; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Stroke Volume; Tetrazoles; Valsartan

We have previously demonstrated that enalapril, α-lipoic acid and menhaden (fish) oil has potential as a treatment for diabetic peripheral neuropathy. In this study we sought to determine the efficacy of these treatments individually or in combination on multiple neuropathic endpoints in a high fat fed low dose streptozotocin treated mouse, a model of type 2 diabetes, following early or late intervention. Four or twelve weeks after the onset of hyperglycemia, diabetic mice were treated with enalapril, α-lipoic acid, menhaden oil or their combination for 12 weeks. Afterwards, endpoints including glucose tolerance, motor and sensory nerve conduction velocity, thermal nociception, and intraepidermal and cornea nerve fiber density was determined. Glucose clearance was impaired in diabetic mice and significantly improved only with combination treatment and early intervention. Diabetes caused steatosis, slowing of motor and sensory nerve conduction velocity, thermal hypoalgesia and reduction in intraepidermal and cornea nerve fiber density. Treating diabetic mice with enalapril, α-lipoic acid or menhaden oil partially protected diabetic mice from these deficits, whereas the combination of these three treatments was more efficacious following early or late intervention. These studies suggest that a combination therapy may be more effective for treating neural complications of type 2 diabetes.

Topics: Acute Disease; Animals; Chronic Disease; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Drug Therapy, Combination; Enalapril; Fish Oils; Hypoglycemic Agents; Male; Mice, Inbred C57BL; Nerve Regeneration; Neuroprotective Agents; Streptozocin; Thioctic Acid; Time Factors

The influence of vinpocetine, pentoxifylline and enalapril on endothelium functions has been studied in a group of in 172 patients with chronic brain ischemia. The endothelium-protective effect of drugs was manifested as the inhibition of the Willebrand factor output during arteriovenous occlusion test and as the renewal of endothelium-depended vasodilation. The extent of neurologic deficit reduction correlated with decrease in the activated endothelium-depended output of the Willebrand factor.

Topics: Adult; Aged; Antihypertensive Agents; Brain Ischemia; Case-Control Studies; Cerebrovascular Circulation; Cholesterol; Chronic Disease; Dose-Response Relationship, Drug; Enalapril; Endothelium, Vascular; Fibrinogen; Humans; Middle Aged; Pentoxifylline; Treatment Outcome; Vasodilation; Vasodilator Agents; Vinca Alkaloids; von Willebrand Factor

Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure.. To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens.. According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50%, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30% from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg.. 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8%) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes.. In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Creatinine; Diabetes Mellitus; Diuretics; Drug Therapy, Combination; Enalapril; Epidemiologic Methods; Female; Heart Failure; Humans; Lisinopril; Male; Reference Values; Renal Insufficiency; Risk Factors

The study included 56 patients with chronic cerebral ischemia and arterial hypertension. Protective effect of enalapril (enap) on endothelium was apparent as increased fibrinolytic activity of plasma, decreased platelet aggregation amplitude caused by adrenalin and ristocetin, partial restoration of endothelium-dependent vasodilation, and inhibition of Willebrand factor release in the arteriovenous occlusion test. The degree of reduction of neurologic deficit by enalapril correlated with the decrease in Willebrand factor release.

Topics: Aged; Antihypertensive Agents; Brain Ischemia; Chronic Disease; Drug Administration Schedule; Enalapril; Endothelium, Vascular; Humans; Hypertension; Middle Aged; Treatment Outcome; von Willebrand Factor

Renal fibrosis is the final common pathway of chronic kidney disease, and its progression predicts the degree of renal dysfunction. We investigated the renoprotective properties of pirfenidone in a remnant kidney model of chronic renal failure to determine its pharmacological potency compared to enalapril. Five-sixths nephrectomized rats were fed diet containing pirfenidone (approximately 700mg/kg/day) for 8weeks. Pirfenidone steadily inhibited the progression of proteinuria, but not to a significant degree. Pirfenidone prevented the elevation of plasma creatinine and blood urea nitrogen. At the end of the experiment, pirfenidone had reduced systolic blood pressure by means of its renoprotective effect. In a histological study, pirfenidone improved interstitial fibrosis in the renal cortex. These effects were supported by the suppression of the expression of TGF-beta and fibronectin in the mRNA of the kidney. In contrast, pirfenidone had little effect on the expression of alpha-smooth muscle actin, which is one of the proteins responsible for epithelial-mesenchymal transition. This property was confirmed by the TGF-beta-induced transdifferentiation observed in cultured normal rat kidney tubular epithelial NRK52E cells. These results suggest that pirfenidone improves the progression of chronic renal failure via its antifibrotic action, although pirfenidone has less effective TGF-beta-induced epithelial to mesenchymal transdifferentiation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cell Differentiation; Cell Line; Chronic Disease; Disease Progression; Enalapril; Epithelial Cells; Fibrosis; Kidney; Kidney Failure, Chronic; Male; Mesoderm; Nephrectomy; Proteinuria; Pyridones; Rats; Rats, Wistar; Transforming Growth Factor beta

Blockade of the renin-angiotensin system (RAS), the standard treatment for chronic proteinuric nephropathy, slows but may not halt progression of the disease, particularly when therapy is started late. Because vasopressin may also play a role in the progression of renal disease, we measured the effect of a dual V(1a) and V(2) vasopressin receptor antagonist (RWJ-676070) alone or combined with angiotensin-converting enzyme inhibition or angiotensin II type 1 receptor blockade on proteinuria and renal disease progression during overt nephropathy. Twenty-one days after renal mass reduction, a time of established injury, rats were given vehicle, RWJ-676070, enalapril, losartan, RWJ-676070 plus enalapril, or losartan in drinking water for an additional 39 days. RWJ-676070 returned the blood pressure to pre-treatment levels, which were significantly lower than those in vehicle-treated rats. Enalapril, losartan, and the combined therapies reduced blood pressure to a greater extent. RWJ-676070 afforded a partial antiproteinuric effect, which was enhanced by the addition of enalapril or losartan. Renal functional impairment, and glomerular and tubular changes were partially ameliorated by RWJ-676070; parameters significantly improved with either enalapril or losartan alone and improved to a greater extent with the combined therapies. Our findings suggest that vasopressin receptor antagonists could be of additional therapeutic value in the treatment of chronic proteinuric nephropathy.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Biomarkers; Blood Pressure; Body Weight; Chronic Disease; Disease Models, Animal; Disease Progression; Diuresis; Drinking; Drug Therapy, Combination; Eating; Enalapril; Hormone Antagonists; Kidney; Kidney Diseases; Losartan; Male; Nephrectomy; Proteinuria; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Renin-Angiotensin System; Spiro Compounds; Time Factors

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Bisoprolol; Carbazoles; Carvedilol; Chronic Disease; Clinical Trials as Topic; Drug Therapy, Combination; Enalapril; Heart Failure; Humans; Professional Practice; Propanolamines

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Drug Therapy, Combination; Enalapril; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Propanolamines; Risk Assessment; Time Factors; Treatment Outcome

Experiments were designed to test the hypothesis that antioxidant treatment would increase the anti-hypertensive actions of endogenous kinins during angiotensin converting enzyme (ACE) inhibition. Four groups of rats, all given angiotensin II (Ang II) for 2 weeks, were studied: 1) control, 2) enalapril, 3) tempol or 4) both tempol and enalapril. Ang II significantly increased systolic blood pressure (BP) when compared with the baseline (170+/-8 vs. 128+/-4 mm Hg, P<0.05). Neither enalapril nor tempol alone was able to attenuate the elevation in BP (165+/-7 and 164+/-6 mm Hg, respectively). In contrast, combined administration of tempol and enalapril prevented the increase in BP (137+/-5 mm Hg). Plasma 8-isoprostane increased in Ang II-infused rats when compared with control untreated rats (69+/-14 vs. 23+/-0.5 pg/ml, P<0.05). Tempol alone or tempol plus enalapril significantly attenuated the increase in plasma 8-isoprostane (29+/-6 and 34+/-7 pg/ml, respectively). In additional experiments, we used the bradykinin B(2) antagonist, icatibant to determine if increased B(2) receptor contributes to the anti-hypertensive effect of combined tempol and enalapril in Ang II-infused rats. Icatibant decreased the ability of this combination to lower arterial pressure. Additionally, a significant increase in B(1) receptor protein expression in renal cortex of Ang II-infused rats was observed compared to control suggesting that bradykinin receptor activation could account for the effect of enalapril to enhance the actions of tempol. These data support the hypothesis that combined reduction of superoxide along with enhanced endogenous kinins may facilitate blood pressure lowering in Ang II hypertension.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Antioxidants; Blood Pressure; Bradykinin; Chronic Disease; Cyclic N-Oxides; Dinoprost; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Enalapril; Hydrogen Peroxide; Hypertension; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Receptors, Bradykinin; Spin Labels; Superoxides; Time Factors

Chronic treatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension mediated partly by enhanced angiotensin-I-converting enzyme (ACE) activity. We examined the influence of L-NAME on rat liver morphology, on hepatic glycogen, cholesterol, and triglyceride content, and on the activities of the cytochrome P450 isoforms CYP1A1/2, CYP2B1/2, CYP2C11, and CYP2E1. Male Wistar rats were treated with L-NAME (20 mg/rat per day via drinking water) for 2, 4, and 8 weeks, and their livers were then removed for analysis. Enzymatic induction was produced by treating rats with phenobarbital (to induce CYP2B1/2), beta-naphthoflavone (to induce CYP1A1/2), or pyrazole (to induce CYP2E1). L-NAME significantly elevated blood pressure; this was reversed by concomitant treatment with enalapril (ACE inhibitor) or losartan (angiotensin II AT(1) receptor antagonist). L-NAME caused vascular hypertrophy in hepatic arteries, with perivascular and interstitial fibrosis involving collagen deposition. Hepatic glycogen content also significantly increased. L-NAME did not affect fasting glucose levels but significantly reduced insulin levels and increased the insulin sensitivity of rats, based on an intraperitoneal glucose tolerance test. Immunoblotting experiments indicated enhanced phosphorylation of protein kinase B and of glycogen synthase kinase 3. All these changes were reversed by concomitant treatment with enalapril or losartan. L-NAME had no effect on hepatic cholesterol or triglyceride content or on the basal or drug-induced activities and protein expression of the cytochrome P450 isoforms. Thus, the chronic inhibition of NO biosynthesis produced hepatic morphological alterations and changes in glycogen metabolism mediated by the renin-angiotensin system. The increase in hepatic glycogen content probably resulted from enhanced glycogen synthase activity following the inhibition of glycogen synthase kinase 3 by phosphorylation.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Chronic Disease; Cytochrome P-450 Enzyme System; Enalapril; Enzyme Activation; Enzyme Inhibitors; Fasting; Glucose; Glycogen; Glycogen Synthase Kinase 3; Hypertension; Hypertrophy; Liver; Liver Cirrhosis; Losartan; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Peptidyl-Dipeptidase A; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Renin-Angiotensin System

The aim of the article was to assess the efficacy of treatment of atrial fibrillation (AE) and congestive heart failure (CHF) with Enalapril in combination with Cordaron. For this reason 62 patients from 37 to 70 years old (mean age 54, 6 +/- 6,1) with CHF (class II-III NYHA) and persistent AF underwent the medical treatment. The suggested scheme of treatment improved HF functional class by NYHA, raised anti reactive effectiveness and favorably influenced on the diastolic function of the LV in this type of patients.

Topics: Adult; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Pressure; Chronic Disease; Drug Therapy, Combination; Echocardiography; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged

1. The aim of the present study was to evaluate the effect of treatment with enalapril on the sensitivity of cardiopulmonary reflexes 30 days after myocardial infarction in Wistar rats. 2. Animals were divided into four groups: (i) sham operated, receiving vehicle (SHAM); (ii) infarcted, receiving vehicle (0.9% NaCl; INF); (iii) sham operated, receiving enalapril (SHAME); and (iv) infarcted, receiving enalapril (INFE). 3. Enalapril was administered at a dose of 10 mg/kg per day. Serotonin (4-32 microg/kg, i.v.) was administered in order to activate the Bezold-Jarisch reflex, which was estimated as the percentage of reduction in heart rate. 4. The volume-sensitive cardiopulmonary reflex was induced by saline overload and evaluated as the percentage increase in sodium and volume renal excretion. At the end of the experiments, rats were killed and hearts excised to estimate the size of the infarction. The weight of the kidneys, lungs, liver and cardiac chambers as ratios of bodyweight was used to estimate the extent of hypertrophy. 5. The results showed an impairment in the sensitivity of the cardiopulmonary reflexes in the INF group compared with the SHAM and SHAME groups. We observed right ventricle and pulmonary hypertrophy, a reduction in mean and systolic arterial pressure and an increase in heart rate in INF animals. In the INFE group, nearly all the parameters were normal compared with the INF group, except for systolic arterial pressure, which was only partially improved. 6. The main finding of the present study was that treatment with enalapril normalized the sensitivity of the cardiopulmonary reflexes, which could be due, in part, to the reduction of cardiac hypertrophy. The present study provides information about the beneficial effects of the angiotensin-converting enzyme inhibitors by normalizing the cardiopulmonary reflexes involved with the regulation of volume and sodium, as well as control of arterial pressure and heart rate in infarcted animals.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Baroreflex; Blood Pressure; Cardiomegaly; Chronic Disease; Disease Models, Animal; Enalapril; Heart Rate; Kidney; Lung; Male; Myocardial Infarction; Natriuresis; Rats; Rats, Wistar; Reflex; Sympathetic Nervous System; Urination; Water-Electrolyte Balance

Previous studies have shown that the renin-angiotensin system (RAS) is activated in diabetes and this may contribute to the subcellular remodelling and heart dysfunction in this disease. Therefore, we examined the effects of RAS blockade by enalapril, an angiotensin-converting enzyme inhibitor, and losartan, an angiotensin receptor AT1 antagonist, on cardiac function, myofibrillar and myosin ATPase activity as well as myosin heavy chain (MHC) isozyme expression in diabetic hearts. Diabetes was induced in rats by a single injection of streptozotocin (65 mg/kg; i.v.) and these animals were treated with and without enalapril (10 mg/kg/day; oral) or losartan (20 mg/kg/day; oral) for 8 weeks. Enalapril or losartan prevented the depressions in left ventricular rate of pressure development, rate of pressure decay and ventricular weight seen in diabetic animals. Both drugs also attenuated the decrease in myofibrillar Ca2+-ATPase, Mg2+-ATPase and myosin ATPase activity seen in diabetic rats. The diabetes-induced increase in beta-MHC content and gene expression as well as the decrease in alpha-MHC content and mRNA levels were also prevented by enalapril and losartan. These results suggest the occurrence of myofibrillar remodelling in diabetic cardiomyopathy and provide evidence that the beneficial effects of RAS blockade in diabetes may be associated with attenuation of myofibrillar remodelling in the heart.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Chronic Disease; Diabetes Mellitus, Experimental; Enalapril; Gene Expression; Heart Ventricles; Losartan; Male; Myofibrils; Myosin Heavy Chains; Myosins; Rats; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; RNA, Messenger

Diabetes mellitus is a predictor of morbidity and mortality in patients with heart failure. The effect of angiotensin-converting enzyme (ACE) inhibitors on the prevention of diabetes in patients with left ventricular dysfunction is unknown. The aim of this retrospective study was to assess the effect of the ACE inhibitor enalapril on the incidence of diabetes in the group of patients from the Montreal Heart Institute enrolled in the Studies of Left Ventricular Dysfunction (SOLVD).. Clinical charts were evaluated for fasting plasma glucose (FPG) levels by blinded reviewers. A diagnosis of diabetes was made when a FPG > or =126 mg/dL (7 mmol/L) was found at 2 visits (follow-up, 2.9+/-1.0 years). Of the 391 patients enrolled at the Montreal Heart Institute, 291 were not diabetic (FPG <126 mg/dL without a history of diabetes), 153 of these were on enalapril and 138 were on placebo. Baseline characteristics were similar in the 2 groups. Forty patients developed diabetes during follow-up, 9 (5.9%) in the enalapril group and 31 (22.4%) in the placebo group (P<0.0001). By multivariate analysis, enalapril remained the most powerful predictor for risk reduction of developing diabetes (hazard ratio, 0.22; 95% confidence intervals, 0.10 to 0.46; P<0.0001). The effect of enalapril was striking in the subgroup of patients with impaired FPG (110 mg/dL [6.1 mmol/L] < or =FPG <126 mg/dL) at baseline: 1 patient (3.3%) in the enalapril group versus 12 (48.0%) in the placebo group developed diabetes (P<0.0001).. Enalapril significantly reduces the incidence of diabetes in patients with left ventricular dysfunction, especially those with impaired FPG.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Chronic Disease; Diabetes Mellitus; Enalapril; Female; Heart Failure; Humans; Incidence; Male; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Ventricular Dysfunction, Left

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Cardiomyopathy, Dilated; Chronic Disease; Dose-Response Relationship, Drug; Enalapril; Endothelium, Vascular; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Muscle, Smooth, Vascular; Myocardial Ischemia; Oxygen Consumption; Pulmonary Wedge Pressure; Severity of Illness Index; Stroke Volume; Treatment Outcome; Vasodilation

Weight loss in chronic heart failure is linked to impaired survival. We aimed to assess the frequency of weight loss in patients with this disease, whether the degree of weight loss predicts mortality, and whether weight loss can be prevented by angiotensin-converting-enzyme (ACE) inhibitors.. We investigated weight changes in 1929 patients from the SOLVD trial who had chronic heart failure, were free of oedema at baseline, and survived for at least 4 months after trial entry. Meanfollow-up was 35 months (SD 13). We analysed the effect of weight loss at cutpoints of 5%, 7.5%, 10%, 15% (a priori), and 6% (post hoc) to identify which one best predicted outcome. To validate results, we analysed data for 619 patients in the V-HeFT II trial.. 817 (42%) patients in the SOLVD trial had weight loss from baseline of 5% or more. At 8 months follow-up, all cutpoints for weight loss were significantly associated with impaired survival after adjustment for age, sex, New York Heart Association class, left ventricular ejection fraction, and treatment allocation. Weight loss of 6% or more at any time during follow-up was the strongest predictor of impaired survival (adjusted hazard ratio 2.10, 95% CI 1.77-2.49; p<0.0001). Patients on the ACE inhibitor enalapril had a lower hazard of 6% or more weight loss than did those not taking the drug (adjusted reduction 19%, p=0.0054). Results from analyses of V-HeFT II data lent support to our findings.. Weight loss occurs frequently in patients with chronic heart disease, its reversal is rare, and when present, it is independently linked to impaired survival. Weight loss of more than 6% should be used to define the presence of cachexia in patients with chronic heart failure. In chronic heart failure, treatment with an ACE inhibitor reduces the risk of weight loss.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Data Interpretation, Statistical; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Male; Middle Aged; Prognosis; Randomized Controlled Trials as Topic; Survival Analysis; Weight Loss

By inhibiting prostaglandin synthesis, aspirin can interfere with both arterial functional and angiotensin-converting enzyme inhibitor (ACEI) properties and be deleterious in chronic heart failure (CHF).. Our aim was to prospectively evaluate the effect of aspirin on arterial functional properties in CHF patients treated with ACEIs.. Over three consecutive treatment periods of 7 days, 18 patients received placebo, followed by aspirin 100 mg/day, and then aspirin 325 mg/day. Single blind prospective assessment of reflected wave and time reflection by radial applanation tonometry; pulse wave velocity; blood pressure; thromboxane B2 (TxB2) and prostaglandins in plasma and urine was performed. Aspirin 325 mg/day induced a significant increase in augmentation index of reflected wave (P<0.0001 and P=0.0013 vs. placebo and aspirin 100 mg, respectively) and a significant decrease in reflected wave traveling times (P=0.0007 vs. placebo). Aspirin 100 mg/day produced a similar, though non-significant, trend in these parameters compared with placebo. Both aspirin treatments produced a statistically significant decrease in serum TxB2 (P<0.0001) but did not have an effect on the metabolite of prostaglandin I2 (P=0.136).. This study demonstrates the existence of a dose-mediated deleterious effect of aspirin upon arterial functional properties in CHF patients treated with ACEI.

Topics: Adult; Aged; Aged, 80 and over; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Arteries; Aspirin; Blood Pressure; Chronic Disease; Controlled Clinical Trials as Topic; Cyclooxygenase Inhibitors; Diastole; Dose-Response Relationship, Drug; Enalapril; Endpoint Determination; Female; Heart Failure; Heart Rate; Humans; Lisinopril; Male; Manometry; Middle Aged; Observer Variation; Prospective Studies; Ramipril; Renin; Reproducibility of Results; Single-Blind Method; Systole; Thromboxane B2; Time Factors; Treatment Outcome

86 patients with chronic obstructive pulmonary diseases (COPD) and tuberculosis in combination with COPD complicated by chronic pulmonary heart (CPH) received a 18-month continuous treatment with enalapril (enap, D. Reddis Laboratories). It was found that the addition of enap, an inhibitor of ACE, to combined therapy of CPH patients is pathogenetic as it results in lowering of blood pressure in pulmonary artery, remodeling of hypertrophic right ventricle of the heart and decline of left ventricular dysfunction, in improvement of functional state of the lungs, in arrest of progression of cardiac failure. Long-term administration of the drug induced no serious side effects and is well tolerated.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Chronic Disease; Combined Modality Therapy; Cough; Enalapril; Humans; Hyperventilation; Middle Aged; Pulmonary Disease, Chronic Obstructive; Pulmonary Heart Disease; Time Factors; Treatment Outcome; Tuberculosis, Pulmonary; Ventricular Remodeling

The efficacy of ACE inhibitors (ACEIs) in the treatment of chronic heart failures is well documented. However, ACEIs may provide incomplete blockade of the renin-angiotensin system (RAS) because of the alternative pathways for angiotensin II (All) production. We hypothesized that more complete blockade of RAS by adding an AT1 receptor blocker (ARB) may have greater potential to decrease mortality associated with heart failure and improve cardiac function than monotherapy with ACEIs. The objective of this study was to evaluate the effect of combined therapy on cardiac functions and survival in cardiomyopathic hamsters. Male cardiomyopathic hamsters (BIO TO2) were administered either placebo (group C), enalapril (30 mg/kg/day) (group E), or enalapril (30 mg/kg/day) + valsartan (500 mg/ kg/day) (group EV), starting at the age of 6 weeks. Kaplan-Meier analysis was performed to assess the differences in survival. Cardiac functions were evaluated by echocardiogram and cardiac catheterization. Group EV showed significant increases in fractional shortening, LV dP/dTmax, and deceleration time, and showed significant decreases in left ventricular diastolic dimension, LV dP/dTmin, and early diastolic mitral velocity/atrial systolic velocity. Treatment with enalapril resulted in longer survival compared with placebo. Moreover, life expectancy (median probability of survival: 433 days) increased significantly in group EV compared with group E (P<0.05) as well as group C (P<0.001). It is concluded that combined therapy improved cardiac function and survival compared to placebo or enalapril monotherapy.

Topics: Angiotensin I; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathy, Dilated; Cell Count; Chronic Disease; Cricetinae; Drug Therapy, Combination; Echocardiography, Doppler; Enalapril; Fibrosis; Hemodynamics; Male; Myocytes, Cardiac; Random Allocation; Receptors, Angiotensin; Renin-Angiotensin System

To evaluate peculiarities and trends in 24-hour arterial pressure (AP) profile and bronchoobstructive syndrome (BOS) in patients with chronic obstructive pulmonary diseases (COPD) and arterial hypertension (AH) on combined treatment including enalapril maleate.. Changes in BOS as shown by clinical data, data of peakflowmetry and external respiration function as well as in AP 24-hour profile according to 24-hour monitoring were studied in 50 patients with exacerbation of bronchial asthma and chronic bronchitis treated for 4 weeks with conventional broncholytic and antiinflammatory modalities, in 28 patients with mild and moderate AH receiving combined therapy including enalapril maleate.. In exacerbation of COPD, 24-h AP profile is characterized by high frequency of the curve "non-dipper". Concomitant mild and moderate AH was diagnosed in more than half of the examinees. The addition of enalaprile maleate to the treatment in many cases lowered systolic and diastolic AP, normalized sympathicoadrenal system and 24-hour AP rhythm, reduced dyspnea, improved exercise tolerance, sleep. Good tolerance of the drug was seen in patients with exacerbation of COPD.. In exacerbation of COPD it is recommended to monitor AP for 24 hours for early detection of AH and initiation of combined treatment with correction of bronchoobstructive syndrome and hemodynamic disorders. As a hypotensive drug, enalapril maleate is adequate in such patients.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Asthma; Blood Pressure; Bronchitis, Chronic; Chronic Disease; Circadian Rhythm; Enalapril; Female; Humans; Hypertension; Lung Diseases, Obstructive; Male; Middle Aged

Plasma aldosterone escape is found during long-term ACE inhibitor therapy of chronic heart failure. Evidence for aldosterone production in cardiovascular tissues raised the question of whether aldosterone escape occurs or not in these tissues. Rats with infarction-induced chronic heart failure were treated with enalapril (20 mg/kg/d) and losartan (15 mg/kg/d) for 20 weeks. Untreated chronic heart failure and sham-operated rats were used as positive and normal controls, respectively. Ex vivo mesenteric artery and heart perfusion, high performance liquid chromatography, and RIA for aldosterone were performed. Chronic heart failure due to myocardial infarction was associated with tissue-specific activation of cardiovascular aldosterone synthesis. In the mesenteric artery, enalapril significantly inhibited aldosterone production compared to untreated, chronic heart failure rats, and losartan lowered aldosterone production to that of sham rats. In myocardium, enalapril failed to significantly inhibit aldosterone production, and losartan significantly inhibited aldosterone production compared to untreated, chronic heart failure rats. These results provide the first evidence that long-term ACE inhibition therapy induces aldosterone escape in myocardium but not in mesenteric artery of chronic heart failure. The angiotensin II subtype 1 receptor blocker losartan tranquilized aldosterone levels in the cardiovascular tissues of chronic heart failure rats.

Topics: Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiac Output, Low; Cardiomegaly; Cardiovascular System; Chronic Disease; Enalapril; Losartan; Male; Mesenteric Arteries; Myocardial Infarction; Rats; Rats, Wistar

Body wasting is a clinical feature of a variety of chronic illnesses including congestive heart failure. The wasting associated with chronic congestive heart failure (cardiac cachexia) has recently been shown to portend a worse prognosis, and it is an independent predictor of mortality. The mechanisms underlying cardiac cachexia are multi-factorial, including metabolic, nutritional, neuroendocrine and immunological aberrations. There is, however, no direct evidence that current medical treatment reverses cachexia in chronic heart failure.. The effect of enalapril, digoxin and frusemide combination on clinical, biochemical and anthropometric indices were determined in eight cachectic Nigerians with chronic congestive heart failure [body mass index (BMI) 20.80+/-2.7 kg/m(2), left ventricular ejection fraction 29+/-4% and LV mass index 161+37 g/m(2)] at baseline, and again after 3 and 6 months of therapy. Ten age- and sex-matched healthy volunteers whose anthropometric data were concurrently measured served as controls.. The anthropometric and clinical measurements were significantly (P<0.001) reduced in heart failure compared to the healthy controls. Congestive hepatomegaly significantly regressed from 161+/-20 mm to 123+/-13 mm after 6 months therapy (P<0.001 ANOVA). There was a significant increase in the sum of four skin fold thickness from 27.6+/-3.3 mm to 30.1+/-3.9 mm at 6 months (P<0.001 ANOVA) 95% confidence intervals for the difference being 1.42 to 3.4 mm. There was a significant increase in the mid-upper arm circumference (P<0.001 ANOVA) with a 95% confidence interval of 0.87-2.1 cm, and a similar trend for increased mid-thigh circumference (95% confidence limits 0.93-5.30 cm) was apparent. Plasma albumin and sodium increased significantly (P<0.05) from 30.1+/-3.8 g/l and 136+/-5.9 mmol/l to 32.9+/-2.5 g/l and 139+/-3.9 mmol/l, respectively. There was a positive and significant correlation between the treatment induced increases in plasma albumin and the increase in mid-upper arm circumference (y=0.25x+0.8, r=0.76, P=0.03 ANOVA) but not with the change in skin fold thickness.. The preliminary results demonstrate increased subcutaneous fat (increased skin fold thickness), greater muscle bulk (increased mid-upper arm and thigh circumferences) together with a significant elevation in plasma albumin and the hematocrit, which reflect the anabolic state in patients treated with ACE inhibitor-digoxin-diuretic with congestive heart failure.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anthropometry; Body Mass Index; Cachexia; Cardiotonic Agents; Chronic Disease; Confidence Intervals; Digoxin; Diuretics; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Failure; Humans; Linear Models; Male; Middle Aged; Nutrition Assessment; Serum Albumin; Skinfold Thickness; Sodium; Treatment Outcome

Hyperoxaluria is a recognized cause of tubulointerstitial lesions and it may contribute to chronic renal failure. In previous studies we demonstrated that enalapril was effective against the progression of tubulointerstitial lesions in a 4-week hyperoxaluria rat model. We evaluated whether the action of enalapril on the tubulointerstitial lesions produced by hyperoxaluria persisted for a long period.. Two-month-old male Sprague-Dawley rats were divided into 4 groups of 12 each, including 1--control animals given tap water, 2--animals with hyperoxaluria, 3--animals with hyperoxaluria plus enalapril, 4--animals with enalapril. Hyperoxaluria in groups 2 and 3 rats was induced by administering 1% ethylene glycol, a precursor for oxalates, in the tap water continuously throughout the whole study. Meanwhile, groups 3 and 4 received 20 mg./l. enalapril in the drinking water. At the end of the study renal tubulointerstitial lesions were evaluated by immunostaining using monoclonal antibodies against macrophage infiltrates (ED1), tubulointerstitial alpha-smooth muscle actin and transforming growth factor-beta1. The lesions were quantified by semiquantitative scores. Creatinine clearance and urinary albumin excretion were also determined.. There was no difference in urine oxalate excretion in groups 2 and 3. Group 3 rats treated with enalapril showed fewer tubulointerstitial lesions than nontreated group 2 rats, as indicated by the mean scores plus or minus standard error of mean for inflammatory infiltrate (2.16 +/- 0.2 versus 0.83 +/- 0.16), tubular atrophy (2 +/- 0.27 versus 0.66 +/- 0.14), interstitial fibrosis (2.5 +/- 0.15 versus 0.5 +/- 0.1), glomerular ED1 (1.75 +/- 0.25 versus 0.16 +/- 0.11), interstitial ED1 (2.33 +/- 0.18 versus 0.58 +/- 0.10) tubular transforming growth factor-beta1 (2.09 +/- 0.08 versus 0.91 +/- 0.14), interstitial transforming growth factor-beta 1 (2.33 +/- 0.22 versus 0.66 +/- 0.12), tubulointerstitial alpha-smooth muscle actin (2.91 +/- 0.22 versus 0.83 +/- 0.16), lower urinary albumin excretion (35.5 +/- 2.7 mg. daily versus 10.9 +/- 1) and higher creatinine clearance (2.29 +/- 0.04 ml. per minute versus 2.54 +/- 0.03, all p <0.05).. Based on our results we believe that enalapril would provide a beneficial effect against chronic tubulointerstitial lesions caused by oxalates.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Chronic Disease; Disease Models, Animal; Enalapril; Hyperoxaluria; Immunohistochemistry; Kidney Function Tests; Male; Nephritis, Interstitial; Probability; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Sensitivity and Specificity; Treatment Outcome; Urinalysis

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Drug Therapy, Combination; Enalapril; Female; Humans; Kidney Diseases; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Proteinuria; Spironolactone

Despite considerable progress in immunosuppression, the incidence of chronic renal allograft rejection has not decreased. Recent studies have revealed that angiotensin-converting enzyme (ACE) inhibition ameliorates graft arteriosclerosis, glomerulosclerosis, and tubular atrophy. Moreover, it decreases systemic and glomerular capillary hydrostatic pressure in a rat kidney allograft model. We evaluated the effects of the ACE inhibitor enalapril on cytokine and growth factor expression in chronically rejecting rat kidney allografts.. Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (Lew) rats. To prevent acute rejection, cyclosporine A (1.5 mg/kg/day) was given to all recipients during the first 10 days after transplantation. Enalapril (60 mg/L) or vehicle was added to the drinking water 10 days after transplantation. Animals were harvested 20 weeks after transplantation for histologic and immunohistologic studies, as well as for evaluation of cytokine and growth factor mRNA by semiquantitative polymerase chain reaction.. Controls developed severe signs of chronic rejection, such as glomerular and vascular lesions, associated with a large number of infiltrating leukocytes. Enalapril-treated animals developed less proteinuria and other signs of chronic rejection. The mRNA levels of transforming growth factor-beta 1 (TGF-beta 1), platelet-derived growth factor A and B chain (PDGF A and B), insulin-like growth factor-I (IGF-I), interleukin-1 (IL-1), and monocyte chemoattractant protein-1 (MCP-1) were significantly reduced in the enalapril group and were most pronounced for IL-1 and PDGF A. In addition, we found an increased level of renal angiotensinogen mRNA after treatment with enalapril.. Treatment with enalapril attenuated the development of proteinuria, ameliorated morphological damage, decreased leukocyte infiltration, and prevented a rise in renal mRNA levels of growth factors and cytokines in kidney grafts in a rat model of chronic renal allograft rejection.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Chronic Disease; Diuresis; Enalapril; Graft Rejection; Growth Substances; Kidney; Kidney Transplantation; Male; Proteinuria; Rats; Rats, Inbred F344; Rats, Inbred Lew; RNA, Messenger

Inhibition of dopamine beta-hydroxylase (DBH) results in a decrease in norepinephrine synthesis. The present study was a randomized, blinded, placebo-controlled investigation of the long-term effects of therapy with the DBH inhibitor nepicastat (NCT) on the progression of left ventricular (LV) dysfunction and remodeling in dogs with chronic heart failure (HF).. Moderate HF (LV ejection fraction [LVEF] 30% to 40%) was produced in 30 dogs by intracoronary microembolization. Dogs were randomized to low-dose NCT (0.5 mg/kg twice daily, n=7) (L-NCT), high-dose NCT (2 mg/kg twice daily, n=7) (H-NCT), L-NCT plus enalapril (10 mg twice daily, n=8) (L-NCT+ENA), or placebo (PL, n=8). Transmyocardial (coronary sinus-arterial) plasma norepinephrine (tNEPI), LVEF, end-systolic volume, and end-diastolic volume were measured before and 3 months after initiating therapy. tNEPI levels were higher in PL compared with NL (86+/-20 versus 13+/-14 pg/mL, P:<0.01). L-NCT alone and L-NCT+ENA reduced tNEPI toward normal (28+/-4 and 39+/-17 pg/mL respectively), whereas HD-NCT reduced tNEPI to below normal levels (3+/-10 pg/mL). In PL dogs, LVEF decreased but was unchanged with L-NCT and increased with L-NCT+ENA. L-NCT and L-NCT+ENA prevented progressive LV remodeling, as evidenced by lack of ongoing increase in end-diastolic volume and end-systolic volume, whereas H-NCT did not. In dogs with HF, therapy with L-NCT prevented progressive LV dysfunction and remodeling. The addition of ENA to L-NCT afforded a greater increase in LV systolic function. NCT at doses that normalize tNEPI may be useful in the treatment of chronic HF.

Topics: Animals; Chronic Disease; Disease Models, Animal; Disease Progression; Dogs; Dopamine beta-Hydroxylase; Dose-Response Relationship, Drug; Enalapril; Enzyme Inhibitors; Heart Failure; Imidazoles; Norepinephrine; Stroke Volume; Thiones; Ventricular Dysfunction, Left; Ventricular Function, Left

Changes in 24-h profiles of arterial pressure following treatment with zolpidem were studied in 12 patients with essential arterial hypertension and chronic sleep problems on enalapril. One week treatment with zolpidem improved quality of sleep, increased a circadian index of systolic arterial pressure, 3 non-dipper patients recovered circadian rhythm of arterial pressure. The antihypertensive effect at night was higher when enalapril was used in combination with zolpidem than in monotherapy with enalapril.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertension; Hypnotics and Sedatives; Male; Middle Aged; Pyridines; Sleep Wake Disorders; Zolpidem

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Chronic Disease; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Hypertension, Pulmonary; Male; Middle Aged; Phenyl Ethers; Treatment Outcome

Chronic severe subclinical systemic hypertension was diagnosed in a 28-yr-old male western lowland gorilla (Gorilla gorilla gorilla). Thoracic radiography, electrocardiography, and echocardiography revealed an enlarged heart with a hypertrophied left ventricle, mitral regurgitation, and a persistent left bundle branch block. Enalapril, later combined with nifedipine, was of some value in reducing the hypertension, with partial reversal of cardiac enlargement and resolution of the bundle branch block. Two years after initiation of treatment, the gorilla developed lethargy and dyspnea. The diagnosis of heart failure was confirmed under anesthesia; the gorilla did not recover and was euthanized. Postmortem examination confirmed congestive heart failure with chronic, fibrosing cardiomyopathy similar to that in other gorillas.

Topics: Animals; Animals, Zoo; Antihypertensive Agents; Ape Diseases; Blood Pressure Determination; Chronic Disease; Drug Therapy, Combination; Echocardiography; Electrocardiography; Enalapril; Euthanasia; Fatal Outcome; Gorilla gorilla; Heart Failure; Hypertension; Male; Myocardium; Nifedipine; Radiography, Thoracic; Vasodilator Agents

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Chronic Disease; Cough; Enalapril; Female; Humans

Angiotensin-converting enzyme inhibitors have been shown to have beneficial effects in the short- and long-term treatment of adult patients with chronic mitral regurgitation. The safety and efficacy of such treatment have not been established for children. The objective of this study was to assess the effect of the angiotensin-converting enzyme inhibitor enalapril on the severity of valvar mitral regurgitation and the systolic performance of overloaded left ventricle of children.. Ten patients 3 to 16 years of age (mean age 9.6 +/- 3.8 years) with moderate to severe chronic mitral insufficiency were examined by means of Doppler echocardiography before and 2 hours after receiving a single oral dose of enalapril (0.40 mg/kg). Effective regurgitant orifice area, regurgitant volume and fraction, left ventricular end-diastolic and end-systolic volumes indexed for body surface area, left ventricular pump function (total ejection fraction), left ventricular contractility (stress-adjusted velocity of shortening) and afterload (peak systolic and end-systolic circumferential wall stress), and systemic vascular resistance were calculated before and after treatment.. The following values decreased significantly compared with baseline values: effective regurgitant orifice area (36.2 +/- 17.4 versus 25.9 +/- 16.5 mm(2), P =.00008), regurgitant volume (53.6 +/- 27.4 versus 36.1 +/- 24.5 mL, P =.0002), regurgitant fraction (56.7 +/- 14.5% versus 39.9 +/- 17.0%, P =. 0009), left ventricular end-diastolic volume indexed for body surface area (81.3 +/- 17.4 versus 76.1 +/- 16.1 mL/m(2), P =.005), left ventricular end-systolic volume indexed for body surface area (26.7 +/- 9.1 versus 22.6 +/- 8.9 mL/m(2), P =.02), afterload (peak systolic circumferential wall stress 135.8 +/- 15.3 versus 123.5 +/- 19.7 g/cm(2), P =.005; end-systolic circumferential wall stress 57.8 +/- 12.4 versus 48.3 +/- 12.8 g/cm(2), P =.005), and systemic vascular resistance (2012.2 +/- 536.1 versus 1622.7 +/- 389 dyne. sec. cm(-5), P =.005). Left ventricular pump function increased (total ejection fraction 67.6 +/- 5.7% versus 71.7 +/- 6.5%, P =. 005) without significant changes in left ventricular contractility (stress-adjusted velocity of shortening -0.35 +/- 0.8 versus -0.21 +/- 1.3 SD, P not significant).. The data showed that for pediatric patients single-dose treatment with oral enalapril reduces the severity of mitral regurgitation and improves left ventricular loading conditions and systolic performance without impairment of myocardial contractility. Persistence of these unloading effects in long-term therapy might slow the evolution of left ventricular dysfunction caused by overload-induced myocardial damage and possibly delay the time at which surgical repair or replacement of the mitral valve becomes necessary.

Topics: Administration, Oral; Adolescent; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Cardiac Volume; Child; Child, Preschool; Chronic Disease; Echocardiography, Doppler; Enalapril; Female; Hemodynamics; Humans; Male; Mitral Valve Insufficiency; Myocardial Contraction; Severity of Illness Index; Treatment Outcome; Vascular Resistance; Ventricular Function, Left

The cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are increased in the circulation of patients with chronic heart failure. However, their correlation with left ventricular dysfunction has not yet been thoroughly evaluated, and their interrelation with other neurohumoral systems, such as the adrenergic system and endothelin, is unclear. Therefore TNF-alpha, its soluble receptor II, IL-6, big endothelin, and noradrenaline levels were simultaneously measured in venous blood from 65 patients with heart failure in New York Heart Association (NYHA) class II to IV during therapy with digitalis, furosemide, and enalapril. TNF-alpha plasma levels were 3.2+/-0.2 SEM pg/ml in 38 patients in NYHA function class II, 4.0+/-0.3 SEM pg/ml in 16 patients in NYHA function class III, and 5.3+/-0.9 SEM pg/ml in 11 patients in NYHA function class IV (p < 0.001 vs NYHA function class II). IL-6 plasma levels were 3.1+/-0.6 SEM pg/ml in 38 patients in NYHA function class II, 5.2+/-0.8 SEM pg/ml in 16 patients in NYHA function class III, and 13.3+/-3.9 SEM pg/ml in 11 patients in NYHA function class IV (p < 0.0001 vs NYHA function class II andp < 0.0001 vs NYHA class III). Thus both cytokines increased with increasing severity of heart failure, but only IL-6 plasma levels were different in patients in the more severe function classes. TNF-alpha correlated closely with TNF soluble receptor II (r = 0.8, p < 0.0001) and modestly with serum creatinine (r = 0.6, p < 0.0001), whereas IL-6 plasma levels were not statistically related to kidney function. Significant modest correlations were also found among TNF-alpha and IL-6 (r = 0.3, p < 0.01), big endothelin (r = 0.3, p < 0.01), and noradrenaline levels (r = 0.4, <0.001). This study supports the hypothesis that in heart failure both cytokines, TNF-alpha, and IL-6, as well as neurohumoral factors, play a role in the clinical progression of the disease. Thereby levels of TNF-alpha but not IL-6 seem to be related to concomitant kidney dysfunction.

Topics: Adrenergic Agonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiotonic Agents; Chronic Disease; Creatinine; Digitalis Glycosides; Disease Progression; Diuretics; Enalapril; Endothelin-1; Endothelins; Female; Furosemide; Heart Failure; Humans; Interleukin-6; Kidney; Linear Models; Male; Middle Aged; Multivariate Analysis; Neurotransmitter Agents; Norepinephrine; Protein Precursors; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Clinical Trials as Topic; Enalapril; Heart Failure; Humans; Patient Selection; Treatment Outcome

Authors investigated the effect of enalapril (10-20 mg daily) on twenty-nine patients with chronic heart failure in NYHA III-IV stadium who's ejection fraction value was under 40% and had restrictive type of diastolic filling abnormality. Parameters of left ventricular function were measured by echocardiography and the basal data were compared to data detected at the time of 3 and 6 months control. A beneficial effect of enalapril was found on functional cardiac status (reduction in NYHA score), on systolic function (augmentation in ejection fraction and mean mitral anulus motion amplitude). Parallel with the previous parameters in the severity of restrictive diastolic filling alterations (reducing the value of pathologically high E/A ratio and an increasing in deceleration time of early diastolic filling wave) a countable decrease was observed. Authors emphasize the favourable effect of angiotensin converting enzyme inhibitors on chronic heart failure caused by different reasons independently of its severity. The source of drug action is reduction of the preload and afterload as well as keeping under control the harmful ventricular remodelling based on impediment of myocardial angiotensin system.

Topics: Adolescent; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Chronic Disease; Diastole; Echocardiography; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged

Chronic hypoxia induces pulmonary hypertension and right ventricular hypertrophy. These changes are completely reversible, except for persistent myocardial fibrosis. The aim of the present study was to determine whether treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril can reduce the ventricular collagen content in animals recovering from chronic hypoxia. Adult male Wistar rats were exposed to intermittent high-altitude hypoxia simulated in a barochamber (7000 m, 8 hr/day, 5 days a week, 24 exposures), then transferred to normoxia and divided into two groups: (a) treated with enalapril (0.1 g/kg/day for 60 days) and (b) without treatment. The corresponding control groups were kept under normoxic conditions. Enalapril significantly decreased the heart rate, systemic arterial pressure, and absolute left and right ventricular weights in both hypoxic and control rats; on the other hand, the pulmonary blood pressure was unchanged. The content and concentration of collagen was reduced in both ventricles of enalapril-treated hypoxic and control animals by 10-26% compared with the corresponding untreated groups. These data suggest that the partial regression of cardiac fibrosis due to enalapril may be independent of the pressure load.

Topics: Altitude Sickness; Angiotensin-Converting Enzyme Inhibitors; Animals; Body Weight; Chronic Disease; Collagen; Enalapril; Hemodynamics; Hydroxyproline; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Male; Myocardium; Organ Size; Pulmonary Fibrosis; Rats; Rats, Wistar

Our recent study demonstrated that in chronic hypertension, hypertrophy of intracerebral arterioles was associated with an increase in the vascular extracellular matrix proteins: fibronectin, laminin, and collagen IV. An additional cerebral finding in chronic hypertension was hypertensive encephalopathy, in which breakdown of the blood-brain barrier (BBB) to serum proteins occurred in multifocal areas of the cortex and basal ganglia. This study was undertaken to determine which of these alterations were attenuated by antihypertensive therapy.. Two weeks after the surgery to produce chronic renal hypertension, half the hypertensive rats were treated orally with enalapril (30 mg/kg), an angiotensin-converting enzyme inhibitor, for 5 weeks. Rats were perfusion-fixed, and their brains were removed and processed for morphological studies. The effect of treatment on vascular hypertrophy was assessed by quantitative morphometry and on the vascular extracellular matrix proteins and BBB permeability alterations by immunohistochemistry.. There was increased immunoreactivity for laminin, fibronectin, and collagen IV in pial and intracerebral arterioles of untreated hypertensive rats. Immunoreactivity was greatest in arterioles in areas with breakdown of the BBB to serum proteins. Enalapril treatment for 5 weeks resulted in a significant reduction of the mean systolic blood pressure, which was accompanied by attenuation of vascular hypertrophy and attenuation of changes in the vascular extracellular matrix proteins. In addition, there was reduction in the magnitude of BBB breakdown after treatment.. Enalapril treatment had a protective effect and attenuated vascular hypertrophy and the increase in vascular extracellular matrix proteins observed in chronic hypertension. In addition, there was reduction in the magnitude of BBB breakdown.

Topics: Animals; Antihypertensive Agents; Arterioles; Blood Pressure; Blood-Brain Barrier; Cerebrovascular Circulation; Chronic Disease; Enalapril; Extracellular Matrix Proteins; Female; Fibronectins; Hypertension; Rats; Rats, Wistar

The effect of enalapril on cerebral blood flow (CBF) was studied in 11 patients with chronic heart failure (NYHA II or III, dilated cardiomyopathy in 6 and old myocardial infarction in 5). CBF was evaluated by analyzing the Patlak-Plot curve obtained from radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (99mTC-HM-PAO). Cardiac index (CI) and stroke volume (SV) were simultaneously measured by impedance cardiography. These measurements were performed before and at four weeks after daily administration of 5 mg enalapril. The stroke volume, cardiac index, and heart rate were not significantly changed after four weeks of enalapril administration. However, CBF was increased by 6.5% from 36.72 +/- 4.66 to 39.13 +/- 5.65 mL/100g/min (P < 0.05). These results suggest that enalapril increased cerebral blood flow, which was not related to increased cardiac output in congestive heart failure. Patlak-Plot analysis of radionuclide angiography using 99mTC-HM-PAO may be available for quantitative assessment of brain perfusion.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Cardiac Output; Cardiomyopathy, Dilated; Cerebrovascular Circulation; Chronic Disease; Enalapril; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Radionuclide Angiography; Stroke Volume; Technetium Tc 99m Exametazime

This study compared the effects of angiotensin converting enzyme (ACE) inhibitors captopril versus enalapril on left ventricular (LV) muscle mass and LV systolic and diastolic function in 58 patients with primary glomerulonephritis and moderate chronic renal failure. The design was a 6-8 week titration phase and 6-month maintenance phase. Mean myocardial mass calculated by M-mode echocardiography in the captopril group was 153 +/- 26 g/m2 before, and 130 +/- 14 g/m2 after 6 months of treatment, in enalapril group 147 +/- 22 g/m2 before, and 126 +/- 23 g/m2 after 6 months of treatment (p < 0.05). LV ejection fraction, early and late transmitral flow velocities and early to late LV inflow velocities ratio were not significantly affected by both ACE inhibitors.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Captopril; Chronic Disease; Drug Evaluation; Enalapril; Female; Glomerulonephritis; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Remission Induction; Time Factors

Insulin resistance (IR) and secondary hyperinsulinaemia are major risk factors of atherosclerosis and probably also of related glomerulosclerosis. Angiotensin converting enzyme inhibitors (ACEI), while improving IR in essential hypertension, do not improve it in patients with chronic renal disease. Thus, the combination of ACEI and low protein diet was evaluated. Thirty-eight patients with various kidney diseases and mild to moderate impairment of kidney function were included in the study. Thirteen of them suffered from IR. Their dietary protein intake was decreased from > or = 1.0 g/kg/d to 0.6-0.7 g/kg/d. Moreover, they were treated by ACEI enalapril at dosages of 2-10 mg/d depending on the absence/presence and severity of hypertension. The patients were followed for 8 months. No clinically relevant kidney disease progression (KDP) was found. IR patients improved remarkably. IR was examined by the oral glucose tolerance test and glucose, insulin and C-peptide determinations. Their increased plasma triglyceride, VLDL concentrations and proteinuria decreased, HDL concentration increased. Acid-base balance and anaemia did not change. It is concluded that protein restriction in combination with ACEI treatment improve IR and the associated dyslipoproteinaemia and proteinuria.

Topics: Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Combined Modality Therapy; Diet, Protein-Restricted; Enalapril; Female; Humans; Insulin Resistance; Kidney; Kidney Diseases; Kidney Function Tests; Male; Middle Aged

Administration of angiotensin converting enzyme (ACE) inhibitors to patients with congestive heart failure (CHF) is associated to a decrease in the abnormal vasoconstrictor neurohormonal activity. This contributes to the sustained benefits of these drugs on symptoms and survival of patients with CHF. There is little information, however, regarding the effects of ACE inhibition on vasodilator and natriuretic hormones.. To evaluate the chronic effects of enalapril, in addition to digitalis and diuretics in patients with chronic cardiac failure.. Nine patients with an idiopathic dilated cardiomyopathy (8 male, aged 48 to 76 years old) under treatment with digitalis and diuretics, received enalapril 20 mg bid during eight weeks. Before and after this treatment period resting left ventricular ejection fraction, functional class, plasma levels of atrial natriuretic factor and bradykinins (BK) and urinary excretion of kalikreins (BK) and prostaglandin E2 (PGE2) were measured.. After enalapril therapy, there was a significant increase in maximal O2 consumption (14.8 +/- 1.2 to 18.6 +/- 1.5 ml/kg/min, p < 0.05) and radionuclide LV ejection fraction (27.4 +/- 1.1 to 31.4 +/- 0.9% p < 0.05). This was associated with a significant decrease in plasma ANP levels (559 +/- 158 to 178 +/- 54.8 pg/ml) and UK (391 +/- 112 to 243 +/- 92 Cu/24 h).. The decrease in ANP levels, which is a well known marker of prognosis in CHF, could contribute to explain the sustained clinical benefits observed with ACE inhibitors in patients with CHF.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Bradykinin; Cardiac Output, Low; Cardiomyopathy, Dilated; Chronic Disease; Dinoprostone; Enalapril; Female; Humans; Kallikreins; Male; Middle Aged; Oxygen Consumption; Stroke Volume; Vasodilator Agents

To assess non-invasively the effect of enalapril on cardiac sympathetic neuronal uptake function in patients with congestive heart failure, by using [123I]-metaiodobenzylguanidine (MIBG), which is a noradrenaline analogue. Cardiac MIBG uptake was visualised by single photon emission tomography (SPET). In addition, plasma noradrenaline concentration, indicating systemic sympathetic activity, was measured to see whether it was related to cardiac MIBG uptake.. Consecutive patients were treated with enalapril and served as their own controls.. Cardiac unit of a tertiary care centre.. 23 Patients with chronic, mild to moderate, stable congestive heart failure, and a left ventricular ejection fraction less than 40%. Heart failure was caused by ischaemic heart disease or was idiopathic.. Cardiac MIBG SPET was performed and plasma noradrenaline concentration was measured before and after 6 weeks treatment with enalapril.. Cardiac uptake of MIBG was measured by using the left ventricular cavity and a venous blood sample as a reference.. Cardiac uptake of MIBG increased significantly after enalapril treatment, indicating improved cardiac neuronal uptake function. Plasma noradrenaline concentration did not decrease significantly. Cardiac MIBG uptake was not related to plasma noradrenaline concentration.. Cardiac MIBG SPET can be used to assess changes in cardiac sympathetic neuronal uptake function caused by pharmacological intervention. Enalapril seemed to improve cardiac sympathetic neuronal uptake function but did not significantly affect plasma noradrenaline concentrations in a group of patients with predominantly moderate heart failure. These results accord with the hypothesis that restoration of cardiac neuronal uptake of noradrenaline is one of the beneficial effects of enalapril in such patients.

Topics: 3-Iodobenzylguanidine; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Enalapril; Female; Heart; Heart Failure; Humans; Iodine Radioisotopes; Iodobenzenes; Male; Middle Aged; Myocardium; Norepinephrine; Prospective Studies; Sympatholytics; Tomography, Emission-Computed, Single-Photon

By a reciprocal of creatininemia the rate of chronic renal failure progression (CRF) was assessed in 14 patients with nephropathy on enalapril treatment. The day dose ranged from 2.5 to 15 mg. In patients with serum creatinin levels from 0.24 to 0.41 mmol/l (group 1) enalapril significantly inhibited CRF progression, as it did in group 2 (serum creatinin levels from 0.47 to 0.68 mmol/l) but 1 patient. In patients with creatinin levels over 0.71 mmol/l, the influence of enalapril on CRF progression rate was insignificant. All the patients exhibited stabilization of arterial hypertension. Proteinuria diminished in groups 1 and 2, while creatinin clearance decreased in groups 1 and 3. It is inferred that enalapril control of renal function in nephropathy patients is efficient only in early CRF.

Topics: Adult; Chronic Disease; Creatinine; Diabetic Nephropathies; Disease Progression; Enalapril; Female; Glomerulonephritis; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Pyelonephritis; Statistics, Nonparametric

Studies in patients with moderate heart failure have shown a positive relation between atrial size and plasma atrial natriuretic peptide (ANP)(99-126) concentrations; however, the relation of the hormone level and left atrial size and left ventricular function in patients with severe chronic heart failure has not been determined. Fifty-three patients from the Cooperative North Scandinavian Enalapril Survival Study with severe chronic heart failure were evaluated with M-mode echocardiography and determination of plasma concentrations of ANP(99-126). In 35 patients, the plasma level of N-terminal ANP(1-98) was also measured. A significant negative relation was found between ANP(1-98), ANP(99-126), and left atrial diameter (r = -.28, P = .05 and r = -.41, P < .005, respectively). Plasma concentrations of both ANP(1-98) and ANP(99-126) were related to left ventricular systolic function as determined by the systolic time interval index (r = .4, P < .05 and r = .29, P < .05, respectively). A significant improvement of left ventricular systolic function was found in the enalapril group but not in the placebo group. After 6 weeks of therapy, no correlation was found between changes in left atrial size or systolic function or changes in either the ANP(1-98) or ANP(99-126) concentration. The results indicate that high ANP(1-98) or ANP(99-126) plasma concentration is determined by the depressed left ventricular function rather than increased left atrial size in patients with chronic severe heart failure. The findings suggest that the ANP release relation to atrial pressure/atrial size is distorted in severe heart failure.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Chronic Disease; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Peptide Fragments; Protein Precursors; Ultrasonography; Ventricular Function, Left

Antiproteinuria effects of angiotensin-converting enzyme (ACE) inhibitors was studied in 23 patients with chronic nephritis (CN) and 32 patients with diabetic nephropathy (DN). CN patients received Capoten, DN patients were given enalapril. The drugs were also examined for the action on systemic arterial pressure, renal function and intrarenal hemodynamics. Significantly decreased urinary excretion of protein occurred in DN patients on the treatment month 1, in CN subjects on month 3. In both groups ACE inhibitors produced marked hypotensive effect, did not affect renal function, noticeably improved intraglomerular hemodynamics. Hypotensive and antiproteinuria activity of the drugs were unrelated. The mechanism of antiproteinuria action of ACE inhibitors works via normalization of intrarenal hemodynamics. Systemic arterial hypertension seems to be an additional factor aggravating disturbances of intrarenal circulation and provoking proteinuria.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Captopril; Chronic Disease; Diabetic Nephropathies; Drug Evaluation; Enalapril; Female; Glomerulonephritis; Hemodynamics; Humans; Male; Middle Aged; Nephrotic Syndrome; Proteinuria

Topics: Captopril; Chronic Disease; Digoxin; Enalapril; Heart Failure; Humans

The aim of this study was to determine whether or not angiotensin-converting enzyme inhibitor, enalapril, could ameliorate the chronic tubulo-interstitial nephropathy (TIN) in uninephrectomized (UNx) rats. Chronic TIN(M) was induced by 2-bromoethylamine hydrobromide. Rats were assigned to five groups; control, UNx-control (UNxC), UNx treated with enalapril (UNxE), UNxMC and UNxME. Enalapril was given for 12 months as drinking water (50 mg/l). At 6 months, albuminuria in UNxE decreased significantly compared with UNxC, but without change in UNxM rats. By 12 months, although all rats in control, UNxC and UNxE remained alive, 1 and 4 rats died in UNxME and UNxMC, respectively. Albuminuria in UNxC was reduced significantly by enalapril but not in UNxM rats. Both urine volume and urine osmolality became equal to control by enalapril in UNx rats, but not in UNxM rats. Serum cholesterol levels were normalized by enalapril in UNx rats, but not in UNxM rats. Levels of serum creatinine and blood urea nitrogen were invariably higher in UNxM than in UNx rats, irrespective of enalapril. Glomerular sclerosis was statistically decreased by enalapril in both UNx and UNxM rats. Enalapril reduced the overall tubulo-interstitial lesions in UNx rats, but not in UNxM group. However, in UNxM rats tubular changes in medullary portion were significantly ameliorated by enalapril. These data suggest that enalapril has a beneficial effect on chronic TIN in this model.

Topics: Albuminuria; Animals; Cholesterol; Chronic Disease; Drug Evaluation, Preclinical; Enalapril; Kidney; Male; Models, Biological; Nephritis, Interstitial; Osmolar Concentration; Rats; Rats, Wistar; Serum Albumin; Time Factors; Triglycerides

The intrarenal renin-angiotensin system (RAS) may contribute to the pathophysiology of heart failure by the generation of angiotensin II at local sites within the kidneys. Angiotensin II may directly influence renal hemodynamics, glomerular contractility, and tubular sodium reabsorption, thereby promoting sodium and fluid retention in this syndrome. In the present study, we examined components of the circulating RAS as well as the intrarenal expressions of renin and angiotensinogen mRNA in rats with stable compensated heart failure (HF) 12 wk after experimental myocardial infarction. Renal angiotensinogen mRNA level in vehicle-treated HF rats increased 47%, as compared with sham control rats (P = 0.001). The increase in angiotensinogen mRNA levels was more pronounced in animals with medium (46%, P < 0.05) and large (66%, P < 0.05) infarcts than in those with small infarcts (31%, P = NS). There were no differences in liver angiotensinogen mRNA, circulating angiotensinogen, angiotensin II, plasma renin concentration (PRC), kidney renin content (KRC), and renal renin mRNA level between sham and HFv. In addition, in a separate group of rats with heart failure, we demonstrated that renal angiotensin II concentration increased twofold (P < 0.05) as compared with that of age-matched sham operated controls. A parallel group of heart failure rats (HFe, n = 11) was treated with enalapril (25 mg/kg per d) in drinking water for 6 wk before these measurements. Blood pressure decreased significantly during treatment (91 vs. 103 mm Hg, P < 0.05). Enalapril treatment in HF rats increased renin mRNA level (2.5-fold, P < 0.005), KRC (5.6-fold, P = 0.005), and PRC (15.5-fold, P < 0.005). The increase in renal angiotensinogen mRNA level observed in HFv rats was markedly attenuated in enalapril treated HF rats (P < 0.001), suggesting a positive feedback of angiotensin II on renal angiotensinogen synthesis. These findings demonstrate an activation of intrarenal RAS, but no changes in the circulating counterpart in this model of experimental heart failure, and they support the concept that the intrinsic renal RAS may contribute to the pathophysiology in this syndrome.

Topics: Angiotensinogen; Animals; Chronic Disease; Enalapril; Heart Failure; Kidney; Male; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; RNA, Messenger

The antihypertensive efficacy of combination therapy with N-E-A was evaluated during 6 months in 15 patients with hypertension associated with mild to moderate kidney failure. After 6 months a significant reduction of SBP and DBP (p < 0.001), with improvement of creatinine clearance and with no adverse effects on ECG, heart rate and routine laboratory tests test, was observed in 3 patients treated with N 20 mg x 2/d + E 10 mg/d + A 50 mg/d and in 8 patients treated with N 20 mg x 3 + E 10 mg x 2, + A 50 mg x 2. Four patients did not respond to this therapy.

Topics: Adult; Atenolol; Chronic Disease; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertension, Renal; Kidney Diseases; Male; Middle Aged; Nicardipine; Treatment Outcome

Patients with carotid artery occlusive disease (CAOD) may be at increased risk of iatrogenic cerebral hypoperfusion. Using the 133xenon-inhalation technique, we evaluated the effects of enalapril on regional cerebral blood flow (CBF) in 14 patients with chronic hypertension, 7 with CAOD and 7 without CAOD (no CAOD). Regional CBF and blood pressure were measured before and 60 minutes after a single dose of enalapril. Changes in mean arterial pressure after enalapril were not significantly different between the two groups: CAOD -4.67 +/- 8.7 mm Hg, no CAOD -6.18 +/- 8.2 mm Hg. Changes in mean CBF after enalapril were also not statistically different: CAOD -1.0 +/- 3.9, no CAOD 1.0 +/- 2.8. In the CAOD group only, however, changes in CBF were significantly related to increasing age (r = -0.9253, p less than 0.01), such that in patients 65 years or older CBF tended to decrease, whereas in younger patients it increased. Elderly patients with CAOD may be at increased risk of iatrogenic cerebral hypoperfusion, and it may be appropriate to evaluate prospectively the effects of antihypertensive medications on CBF.

Topics: Age Factors; Aged; Aged, 80 and over; Blood Pressure; Carotid Artery Thrombosis; Cerebrovascular Circulation; Chronic Disease; Enalapril; Female; Humans; Hypertension; Male; Middle Aged; Xenon Radioisotopes

The influence of long-term oral administration of enalapril maleate (an angiotensin II-converting enzyme inhibitor) on regional cerebral blood flow (rCBF) was studied in 10 patients with chronic cerebral infarction. The rCBF was measured by a 133Xe inhalation method before and after a mean of sixty-five days' administration of 5 mg of enalapril.. Mean arterial blood pressure (MABP) was mildly decreased in 6 patients, but the average change in MABP was not significant (Endtidal partial pressure of carbon dioxide (PeC02) was not changed significantly. The mean rCBF was increased by 8% after administration of enalapril (0.05 less than p less than 0.1) There was no significant correlation between percent change in MABP and the percent change in rCBF. These results indicate that enalapril has not only antihypertensive action but also a beneficial effect on the cerebral circulation in patients with chronic cerebral infarction.

Topics: Administration, Oral; Aged; Cerebral Infarction; Cerebrovascular Circulation; Chronic Disease; Drug Evaluation; Enalapril; Female; Humans; Hypertension; Male; Middle Aged; Radionuclide Imaging; Xenon Radioisotopes

The diuretic and natriuretic response to an intravenous dose of frusemide 40 mg was assessed in the erect and supine positions in 10 patients with cardiac failure who were being treated with enalapril 10 mg twice daily in addition to diuretics (Enalapril group) and in 10 patients with cardiac failure taking diuretics alone (Control group). Total 4 h diuresis in the erect position was 728 ml and in the supine position was 824 ml in the patients taking enalapril compared to 655 ml in the erect position and 1166 ml in the supine position in those patients taking diuretics alone. Total 4 h natriuresis in the erect positions was 78 mmol and in the supine position was 85 mmol in patients taking enalapril 10 mg twice daily but in those patients taking diuretics alone total 4 h natriuresis in the erect position was 67 mmol increasing to 120 mmol in the supine position. Measurements of plasma renin activity and plasma angiotensin II concentration confirmed effective converting enzyme inhibition, in the group of patients taking enalapril, but in those patients taking diuretics alone the erect position was associated with an increase in plasma renin activity, and plasma concentrations of angiotensin II and aldosterone. We conclude that the renin angiotensin system is a major factor in mediating the effect of posture on loop diuretic drugs.

Topics: Adult; Aged; Aged, 80 and over; Cardiac Output, Low; Chronic Disease; Diuresis; Enalapril; Furosemide; Humans; Male; Middle Aged; Natriuresis; Posture; Renin-Angiotensin System

Eleven patients with coronary artery disease and chronic heart failure were studied before and three months after the angiotensin converting enzyme inhibitor enalapril was added to their frusemide medication. The following were measured: left ventricular pressure and volume with transient occlusion of the inferior vena cava, radionuclide angiography, and hormone concentrations in plasma. As in other reported studies, the clinical condition of the patients improved and their exercise tolerance increased moderately. Addition of enalapril reduced end diastolic and systolic pressure, reduced ventricular volume, and concomitantly increased the ejection fraction. The end systolic pressure-volume relation shifted to the left as it did in a similar animal study. In the animal study unloading by a vasodilator did not induce a leftward shift, so it can be inferred that in the present study unloading combined with a decrease in the angiotensin concentration was instrumental in remodelling the heart. Though unloading was expected to have a beneficial effect on the oxygen supply/demand ratio of the heart, the patients still showed the same drop in the ejection fraction during exercise as they did before treatment with enalapril, and early diastolic filling did not improve. Normally, regression of cardiac dilatation is only found if pump function improves; the present study showed that unloading in combination with angiotensin converting enzyme inhibition reshapes the ventricle without improving intrinsic pump function.

Topics: Aged; Chronic Disease; Enalapril; Exercise; Heart; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Contraction; Ventricular Function

We studied, by 48-hour Holter monitoring, 33 patients with chronic stable heart failure (radionuclide ejection fraction less than 35%), complex ventricular arrhythmias and no electrolyte abnormalities, after a period during which they were treated with digoxin and diuretics. Before Holter monitoring blood samples were analyzed for serum concentration of sodium, potassium, magnesium, urea, creatinine, digoxin, aldosterone and for plasmatic renin activity in addition to urinary aldosterone and catecholamines determination. After these investigations in 23 patients, 5-20 mg of enalapril were progressively added to the conventional therapy, while 10 patients continued the previous therapy. After 8 weeks 30 patients were subjected to a second 48-hour Holter monitoring and to the same biochemical and hormonal tests. One patient died and 2 were lost to follow up. Only the enalapril group showed a significant decrease in the number of premature ventricular complexes (PVC) (p less than 0.01), and the frequency of couplets and episodes of ventricular tachycardia (VT) declined significantly (P less than 0.01). In the two groups there were no significant changes in digoxin, sodium, or magnesium, while potassium concentration increased in both groups (p less than 0.01). In the enalapril group heart rate and systolic and diastolic pressure declined significantly (p less than 0.01), and New York Heart Association class (NYHA) improved (p less than 0.001). In the other group there were no significant changes in these parameters. Enalapril caused a significant increase in the plasmatic renin activity (p less than 0.01) and a significant fall of plasma and urinary aldosterone (p less than 0.01; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Arrhythmias, Cardiac; Blood Pressure; Chronic Disease; Electrocardiography, Ambulatory; Enalapril; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged

Topics: Adult; Captopril; Chronic Disease; Enalapril; Female; Humans; Kidney Failure, Chronic; Male; Nigeria; Proteinuria

1. In addition to their antihypertensive effect, ACE inhibitors have been reported to increase general well-being, general health and vitality and work performance. The cause of these effects is not known. A possible mechanism may be release of beta-endorphins. 2. In the present study changes in plasma concentration of beta-endorphins on days with ACE inhibitor treatment (n = 12) and on non-treatment control days (n = 12) were compared in 6 patients. 3. Both on control and treatment days the beta-endorphin level fell, by 7.1 and 10.0%, respectively, from 8.00 a.m. to 8.00 p.m., reflecting the known diurnal rhythm of this opioid. This difference between the control and treatment days is not statistically significant. 4. The study should be extended to determine endorphin concentration in the cerebrospinal fluid, and other opioids should be looked for.

Topics: Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Enalapril; Endorphins; Female; Heart Failure; Hemodynamics; Humans; Lisinopril; Male

Prolonged treatment with cyclosporine (CS) results in an irreversible renal lesion consisting of interstitial fibrosis and tubular atrophy, as well as prominent hyperplasia of the juxtaglomerular apparatus (JGA). Ischemia to the tubulointerstitial compartment caused by intense CS-mediated renal vasoconstriction may contribute significantly to the development of this lesion. To explore the potential role of volume contraction and activation of the renin-angiotensin system (RAS) in the genesis of this lesion, we have employed a recently described rodent model of chronic cyclosporine nephropathy (CCN). Over 28 days of CS therapy, animals received plain drinking water, 1% saline, or enalapril (ENAL), 50 mg/l in drinking water. At the end of 28 days, Na+ balance in saline-treated animals was markedly positive, and plasma volume was increased; however, glomerular filtration rate (GFR) did not change, and the tubulointerstitial lesion and JGA hyperplasia as evaluated by morphometric techniques were unaffected. Enalapril-treated animals were relatively hypotensive with lower GFR than CS controls. Enalapril conferred no protection against the development of tubulointerstitial disease and exacerbated the development of JGA hyperplasia and hyperkalemia. We conclude that volume contraction is not an important contributor to the reduced GFR, tubulointerstitial lesion, or JGA hyperplasia associated with long-term CS treatment. Blockade of the RAS also conferred no protection against the development of tubulointerstitial disease but resulted in worsening of JGA hyperplasia and hyperkalemia.

Topics: Animals; Blood Pressure; Chronic Disease; Cyclosporins; Enalapril; Kidney; Kidney Diseases; Male; Natriuresis; Plasma Substitutes; Rats; Rats, Inbred Strains; Renin; Sodium Chloride; Time Factors

Five patients, who had never received any drug treatment but who had severe chronic congestive heart failure with salt and water retention, were studied before and after a single dose of enalapril (10 mg orally). Three patients continued on enalapril as monotherapy (10 mg b.d. orally) for one month. Central haemodynamics, body fluid volumes, renal function and plasma hormones were measured at rest. The initial mean right atrial pressure was 13 +/- 4 mm Hg, pulmonary wedge pressure 29 +/- 4 mm Hg and cardiac index 1.8 +/- 0.21/min/m2. Enalapril, given acutely, caused only small changes. Two patients were withdrawn after the single dose of enalapril and treated with diuretics for clinical reasons. The remaining three patients each lost more than 4 kg in weight after one month of treatment with enalapril alone. Total body exchangeable sodium and total body water were reduced but central haemodynamics were unchanged. Although enalapril was of some benefit when given alone to patients with severe congestive heart failure, all five patients were finally treated with diuretics for clinical reasons. Enalapril is not recommended as the initial and only therapy for patients with severe congestive heart failure.

Topics: Adult; Aged; Body Water; Chronic Disease; Diuretics; Enalapril; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Sodium

The ACE-inhibiting drugs enalapril and captopril may result in a chronic and sometimes severe cough for which no pathologic cause can be found. Drug-induced cough should therefore be considered in any symptomatic patient taking these medications. In such cases, prompt withdrawal of the drug and substitution of a non-ACE inhibitor is curative and conserves the time and resources of the patient and the physician by avoiding unnecessary diagnostic and therapeutic measures.

Topics: Aged; Chronic Disease; Cough; Dose-Response Relationship, Drug; Enalapril; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged

Chronic aminonucleoside nephrosis is variably associated with tubulointerstitial damage, depending on the route and frequency of drug administration. Recently, different groups have shown this injurious tubulointerstitial process to be reversible, coinciding with the resolution of heavy proteinuria to normal values. The authors have previously shown that a single jugular intravenous administration of puromycin aminonucleoside (PA) to male Munich-Wistar rats produces a triphasic pattern of glomerular injury and proteinuria, which culminates in focal glomerulosclerosis 70 weeks after drug administration. The authors now report the later progression of the tubulointerstitial morphologic abnormalities associated with acute nephrosis (phase I), despite spontaneous resolution of glomerular injury during the intermediate period (phase II) in this model. Although treatment of rats with the angiotensin I converting enzyme inhibitor enalapril (50 mg/l drinking water) over the 70-week period did not affect the magnitude of proteinuria during the acute nephrotic phase, enalapril prevented the recurrence of proteinuria (phase III), as well as significantly reducing the severity of interstitial fibrosis, extent of tubular dilatation, and number of intratubular casts on semiquantitative scoring at the conclusion of the study. In addition, enalapril-treated rats had less low-molecular-weight protein excretion during the recurrent phase of proteinuria, suggesting a preservation of tubular functional capacity to reabsorb these proteins. In vitro cytotoxicity studies showed only the glomerular visceral epithelial cell to be sensitive to PA, in contrast with rat tubular epithelium and other cellular controls. Although the exact pathogenetic mechanism responsible for the development of the tubulointerstitial damage remains unknown, PA in vitro does not adversely affect rat tubular epithelium; there is however a clear correlation between the magnitude of recurrent proteinuria and the severity of tubulointerstitial morphologic abnormalities, as suggested by the beneficial effect of converting enzyme inhibition on both of these untoward processes.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cell Line; Cell Survival; Chronic Disease; Enalapril; Glomerular Filtration Rate; Kidney; Kidney Tubules; Male; Nephrotic Syndrome; Proteinuria; Puromycin Aminonucleoside; Rats; Rats, Inbred Strains

Physicians should suspect ACE inhibitors as the cause of cough in patients whose symptom begins soon after the institution of therapy with this class of drugs. This is particularly important in patients without a personal or family history of atopy, with normal physical findings, chest radiographs, and lung function tests. Rather than subjecting the patient to an extensive workup, substitution of a different antihypertensive agent is an inexpensive way to show whether the ACE inhibitor is the cause of the chronic cough.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Cough; Enalapril; Female; Humans; Hypertension; Middle Aged

Ten patients (6 men, 4 women, age range 35-64 years) with glomerulopathies were studied. Diagnoses were membranoproliferative glomerulonephritis (GN; n = 4), membranous GN (n = 3), focal and diffuse glomerulosclerosis (n = 2), and poststreptococcal GN (n = 1). These were confirmed by renal biopsy in 8 of the 10 patients. All patients had reduced function (creatinine clearance 15-55 ml/min); proteinuria ranged from 1.0 to 10.4 g/day. Three normotensive patients received enalapril 10 mg once daily. Seven hypertensives received enalapril 10-40 mg once daily to control blood pressure (BP). Concomitant diuretic therapy (furosemide/bumetanide) was administered to 6 patients. There were visits every 14 days for a mean of 15.9 months (range 9-26 months). Diet was monitored, and BP was significantly controlled in the hypertensive patients but not altered in the normotensives. Serum creatinine, blood urea nitrogen, creatinine clearance, and 24-hour urinary protein improved and did not deteriorate progressively. Serum potassium did not change significantly. No adverse clinical events were noted. Enalapril therapy may improve the prognosis for GN over time by maintaining glomerular filtration rate and decreasing proteinuria.

Topics: Adult; Chronic Disease; Creatinine; Enalapril; Female; Glomerulonephritis; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Humans; Hypertension; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Proteinuria; Time Factors

There are several indications that the oxygen supply to the myocardium is inadequate in chronic heart failure. This is due to an increased intramyocardial vascular resistance, elevated filling pressures, and a shortened diastolic perfusion time. In parallel, the myocardial oxygen demand is heightened due to elevated wall stress, heart rate and contractility. This imbalance between myocardial oxygen supply and demand might be the cause of the adaptive metabolic changes seen in severe chronic heart failure. We showed increased LDH 5, decreased LDH 1 and increased ADP/ATP-carrier concentration in the myocardium from patients with chronic heart failure. After ACE-inhibitor treatment in 33 patients with chronic heart failure, LDH 1 increased from 38.7 +/- 6.7% to 42.3 +/- 5.5% (P less than 0.005) paralleled by a decrease in LDH 5 from 20.8 +/- 7.0% to 15.8 +/- 4.7% (P less than 0.001). The ADP/ATP-carrier concentration also decreased significantly within the normal range. This shift in the LDH isoenzyme pattern and decrease in the ADP/ATP-concentration can be interpreted as an indication for an improvement of myocardial energy balance in chronic heart failure under ACE-inhibitor therapy. This might help interrupt the self-perpetuation of chronic heart failure which is partially caused by a progressive subendocardial perfusion deficit.

Topics: Cardiac Output, Low; Chronic Disease; Enalapril; Glucose; Hemodynamics; Humans; Isoelectric Focusing; Isoenzymes; L-Lactate Dehydrogenase; Mitochondrial ADP, ATP Translocases; Myocardium

The objective is here to study the long and intermediate term clinical and haemodynamic effects of enalapril during chronic heart failure resistant to the classic digitalis-diuretics treatment. The study involves 16 patients (12 males and 4 females), with a mean age of 50 years. Before being given enalapril, 12 patients were at stage IV and 4 patients at stage II of the NYHA; the mean capillary pressure was quite elevated (30 +/- 6.3 mmHg), the cardiac index has collapsed (2.12 +/- 0.38 l.min.m2) and the stroke fraction (SF) is 0.28 +/- 0.08. At the 1st month control, there is a definite functional and haemodynamic improvement of the pre-charge as well as the post-charge. This improvement is still present at 6 months. The ventricular function is improved (SF = 0.38 +/- 0.13; p less than 0.001). The clinical tolerance of enalapril is excellent and the only adverse reaction is a transient deterioration of the renal function in a patient with diabetic glomerulopathy.

Topics: Adolescent; Adult; Aged; Chronic Disease; Drug Resistance; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Prospective Studies; Time Factors

We studied the effects of lisinopril on mean arterial blood pressure (MAP), plasma renin activity (PRA), and renal hemodynamics in nine patients with chronic renal disease and hypertension, before, and after three months of therapy. Lisinopril normalized blood pressure in five of nine patients (responders) and did not in the remaining four (nonresponders). PRA rose after lisinopril (4.8 +/- 2.6 ng/mL/h to 25 +/- 15 ng/mL/h, P less than 0.05) in responders, but not in nonresponders (2.0 +/- 1.4 ng/mL/h to 3.4 +/- 2.9 ng/mL/h). Glomerular filtration rate remained stable in both groups (responders: 43 +/- 11 mL/min to 43 +/- 22 mL/min; nonresponders: 39 +/- 25 mL/min to 32 +/- 21 mL/min). In the responders renal hemodynamics remained stable after lisinopril (renal plasma flow: 223 +/- 80 mL/min to 216 +/- 91 mL/min; filtration fraction: .20 +/- .04 to .20 +/- .05; renal vascular resistance: 386 +/- 179 to 326 +/- 209 units). In the nonresponders, renal plasma flow decreased (228 +/- 141 mL/min to 162 +/- 117 mL/min, P less than 0.005), filtration fraction increased (.19 +/- .08 to .24 +/- .12, P less than 0.05), and renal vascular resistance increased (695 +/- 747 to 1265 +/- 1574 units, P less than 0.05) after chronic lisinopril therapy. We conclude (1) there is a heterogeneous response to lisinopril in patients with chronic renal disease and hypertension, (2) lisinopril monotherapy may result in effective blood pressure control without renal hemodynamic compromise, and (3) an increase in PRA following converting enzyme inhibition may identify those in whom the circulating renin angiotensin system is participating in systemic hypertension and intrarenal hemodynamic changes.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Chronic Disease; Drug Evaluation; Enalapril; Glomerular Filtration Rate; Hemodynamics; Humans; Hypertension, Renal; Kidney; Kidney Diseases; Lisinopril; Middle Aged; Potassium; Proteinuria; Renin

Comparative effects of the angiotensin converting enzyme inhibitors captopril and enalapril on progression of chronic renal disease was studied in 3/4 nephrectomized rats. Rats were divided into sham and nephrectomized groups, and treated with plain water or water containing captopril (150 mg/liter) or enalapril (50 mg/liter). Evaluations were made 4 weeks before and 0, 4, 8, and 10 weeks after nephrectomy. Endogenous creatinine clearance decreased in drug-treated, nephrectomized rats to values less than sham controls, but remained greater than water-treated rats. Significant (P less than 0.05) proteinuria developed 4 weeks post-nephrectomy in water-treated rats, 8 weeks post-nephrectomy in captopril-treated rats, but did not develop in enalapril treated rats. Regression analysis of carbamylated plasma protein values vs plasma creatinine revealed significant (P less than 0.05) relationships only in the water-treated, nephrectomized rats from weeks 0 through 8, but were otherwise unaffected by treatment. Both drugs resulted in significantly (P less than 0.05) improved scores for renal histologic lesions as compared to water treatment. Modifications of proteinuria in captopril and enalapril-treated rats occurred prior to onset of changes in systolic blood pressure, which was significantly elevated only in water-treated, nephrectomized rats at weeks 8 and 10. We conclude that angiotensin converting enzyme inhibitors may ameliorate progression of experimental renal disease through intrarenal effects, independent of modulation of systemic blood pressure, and that enalapril may be superior to captopril in some regards.

Topics: Animals; Blood Cell Count; Blood Pressure; Body Weight; Captopril; Chronic Disease; Creatinine; Drinking; Electrolytes; Enalapril; Kidney Diseases; Male; Nephrectomy; Organ Size; Rats; Rats, Inbred Strains; Urodynamics

The hemodynamic response of isosorbide-5-mononitrate (IS-5-MN) to the addition of the widely used therapy of diuretic drugs and the maximally tolerated dose of enalapril for heart failure was assessed in 8 patients with congestive heart failure (CHF) (New York Heart Association class II and III). The diuretic therapy was furosemide, 40 to 80 mg/day, with or without amiloride, 5 to 10 mg/day. The dose of enalapril was 5 to 20 mg/day. Four hours after the administration of the morning dose of enalapril, a Swan-Ganz catheter was positioned in the pulmonary artery. Patients received increasing doses of IS-5-MN to produce a satisfactory decrease in pulmonary capillary wedge pressure. Two of the first 3 patients studied had a large reduction in blood pressure when given 10 mg of IS-5-MN. Subsequent patients were therefore given an initial dose of 5 mg, the total dose being 5 to 20 mg over 2 hours. Results at baseline and 1 hour after the final dose of IS-5-MN are expressed as mean +/- standard deviation. Both pulmonary artery systolic and diastolic pressures decreased significantly (p less than 0.05) by 12.2 +/- 8.9/4.2 +/- 5.2 mm Hg, from 47.2 +/- 16.0/21.6 +/- 6.0 mm Hg to 35.0 +/- 15.2/17.4 +/- 9.3 mm Hg. Pulmonary capillary wedge pressure decreased by 8.6 +/- 4.4 mm Hg, from 22.1 +/- 5.4 to 13.6 +/- 7.5 mm Hg (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blood Pressure; Cardiac Output; Chronic Disease; Diuretics; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Heart Rate; Humans; Isosorbide Dinitrate; Male; Middle Aged; Pulmonary Wedge Pressure

To identify patients with severe chronic heart failure who are at greatest risk of developing functional renal insufficiency during converting enzyme inhibition, creatinine clearance was measured in 59 patients before and after long-term therapy with captopril (39 patients) or enalapril (20 patients), while digitalis and diuretic therapy was kept constant. Creatinine clearance increased or remained constant in 33 of the 59 patients (Group I), but declined in the remaining 26 patients (Group II). The two groups were similar with respect to the cause of heart failure, pretreatment renal function and all pretreatment hemodynamic variables. Patients in Group II, however, had lower values for serum sodium concentration (134.8 +/- 1.0 versus 137.0 +/- 0.6 mmol/liter) and higher values for plasma renin activity (10.6 +/- 3.4 versus 3.0 +/- 0.5 ng/ml per hour), received larger doses of furosemide (108 +/- 11 versus 84 +/- 6 mg/day), were more frequently diabetic (42 versus 15%) and were more frequently treated with enalapril (50 versus 21%) than were patients in Group I (all p less than 0.05). By stepwise logistic analysis, only hyponatremia (or an elevated plasma renin activity) and enalapril therapy independently predicted the decline in creatinine clearance during converting enzyme inhibition. These observations could not be explained by changes in systemic blood pressure. In patients with a normal serum sodium concentration (greater than or equal to 137 mmol/liter), creatinine clearance increased with captopril (+21%, p less than 0.05), but not with enalapril (-6%, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Captopril; Chronic Disease; Enalapril; Female; Heart Failure; Humans; Hyponatremia; Kidney Diseases; Male; Middle Aged; Renin; Risk Factors; Sodium

The effect of clonidine, on alpha 2-agonist and antihypertensive, on the progression of chronic renal disease was studied in rats subjected to partial nephrectomy. Treatments began four weeks after the removal of approximately 70% of renal mass. Clonidine was given once daily by gavage on an increasing dose schedule of 50 micrograms/kg for 4 weeks, followed by 100 micrograms/kg for 8 weeks and finally 200 micrograms/kg for 6 weeks. Measurements of renal functions were made at 4 week-intervals during treatment. After 18 weeks, clonidine-treated rats had lower levels of plasma urea nitrogen (P less than 0.05) and plasma creatinine (P less than 0.05). Urinary protein excretion rates were lower in clonidine-treated rats while receiving 100 micrograms/kg at 8 weeks (P less than 0.05) and 200 micrograms/kg at 18 weeks (P less than 0.05). At the end of the treatment period, anesthetized clonidine-treated rats had a numerically lower mean arterial pressure (p = 0.08), but no difference in the histological ranking of light microscopic lesions (P greater than 0.10). Based on the functional data, we conclude that clonidine retards the deterioration of renal function in this model of chronic renal disease. The lack of a consistent effect of clonidine on proteinuria and no reduction in the severity of morphological damage indicates that clonidine is less effective than previously reported treatment in this model with angiotensin converting enzyme inhibition. These differences in efficacy may be related to differences in intraglomerular hemodynamic alterations and could be an important consideration in the selection of therapies for individuals with hypertension and renal insufficiency.

Topics: Animals; Blood Pressure; Chronic Disease; Clonidine; Creatinine; Enalapril; Heart; Kidney; Kidney Diseases; Male; Nephrectomy; Organ Size; Proteinuria; Rats; Rats, Inbred Strains

During chronic chlorthalidone treatment of patients with essential hypertension, distal tubular sodium reabsorption is continuously inhibited. At the same time, sodium balance is maintained by an increase of the proximal tubular sodium reabsorption. In the present study, we investigated whether this increase is caused by a stimulated renin-angiotensin system (RAS). For this purpose, the renal effects of converting enzyme inhibition (CEI) were evaluated in 12 patients with essential hypertension who remained hypertensive despite chronic chlorthalidone treatment. After 6 weeks of chlorthalidone, an intravenous injection of 10 mg enalaprilic acid decreased the mean arterial pressure (MAP) from 110 to 102 mm Hg. The effective renal plasma flow (ERPF) increased. However, glomerular filtration rate (GFR) and the fractional excretions of sodium, lithium and free water did not change significantly. After 2 additional weeks of chlorthalidone combined with enalapril 20 mg b.i.d., MAP fell to 90 mm Hg, ERPF remained elevated and plasma aldosterone concentration decreased. As in the acute study, no significant changes were detected in the GFR and the fractional excretions of sodium, lithium or free water. Extracellular fluid volume was not diminished during these 2 weeks. Fractional proximal sodium reabsorption during chronic chlorthalidone therapy was higher when calculated from free water clearance (91%) than from the lithium clearance (71%), but neither of the two were affected by acute or chronic CEI. The results of this study suggest that during chronic diuretic treatment, maintenance of sodium balance by increased proximal reabsorption is not dependent on the stimulated RAS, or alternatively, that this function of the RAS is exactly counterbalanced by another effect of CEI, possibly by the fall in blood pressure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Chlorthalidone; Chronic Disease; Diuresis; Diuretics; Drug Therapy, Combination; Enalapril; Enalaprilat; Glomerular Filtration Rate; Humans; Hypertension; Kidney Tubules, Distal; Kidney Tubules, Proximal; Renal Circulation; Renin-Angiotensin System; Sodium

Systemic and coronary hemodynamic, metabolic and humoral effects of a new intravenous angiotensin-converting enzyme inhibitor, enalaprilat, were evaluated in 14 patients with chronic heart failure. Onset of hemodynamic action occurred within 15 minutes and persisted for 6 hours. At the time of peak effect, there was a significant reduction in mean arterial pressure (-21%) and pulmonary capillary wedge pressure (-33%). Systemic vascular resistance decreased by 32% and stroke volume index increased by 20%. These systemic hemodynamic changes indicate improved left ventricular function. There was a substantial sustained reduction in rate-pressure product initially without a change in coronary sinus blood flow or myocardial oxygen consumption. There was also reduced myocardial oxygen extraction and augmented coronary sinus oxygen saturation at 30 minutes and 1 hour. In three patients, abnormal myocardial lactate extraction, present before enalaprilat, changed to uptake after enalaprilat, indicating amelioration of myocardial ischemia that was not clinically manifest. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma renin activity increased and plasma aldosterone decreased. These findings suggest that enalaprilat produces inhibition of the angiotensin-converting enzyme and consequent beneficial systemic hemodynamic changes in heart failure. In some patients with heart failure, silent myocardial ischemia at rest can occur and can be alleviated with enalaprilat. Decreased myocardial oxygen extraction, increased coronary sinus oxygen saturation and lack of expected decrease in coronary sinus blood flow despite reduced rate-pressure product suggest transient coronary vasodilation by enalaprilat.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Catecholamines; Chronic Disease; Coronary Circulation; Enalapril; Enalaprilat; Female; Heart Failure; Hemodynamics; Humans; Infusions, Parenteral; Male; Middle Aged; Myocardium; Renin-Angiotensin System

The renin-angiotensin system is activated in the majority of patients with chronic congestive heart failure. This may be part of the pathophysiology of the disease, a secondary phenomenon, or the result of intense diuretic therapy. Irrespective of the mechanism of renin-angiotensin activation, converting enzyme inhibitors are an effective form of therapy as well as a means to evaluate pathophysiologic mechanisms of congestive heart failure. Because of the activation of the renin-angiotensin system, angiotensin-mediated vasoconstriction and aldosterone-mediated sodium retention can be suppressed and, in some individuals, completely blocked by converting enzyme inhibitors. Improved forward cardiac flow and reduction of pulmonary congestion occur with reversal of vasoconstriction, so that relief of edema, due to enhanced sodium and water excretion, will occur. While it is easy to identify a close correlation between markers of renin-angiotensin activity and the initial response to converting enzyme inhibitors, it is more difficult to identify this response long-term. This may be due to changes in dietary sodium intake, intensity of diuretic therapy, or alteration in renal blood flow and function. Clinically, however, the response to converting enzyme inhibitors is favorable in the majority of people.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Enalapril; Enalaprilat; Enzyme Activation; Heart Failure; Heart Rate; Hemodynamics; Humans; Renin-Angiotensin System; Saralasin; Sodium; Vasoconstriction

Topics: Chronic Disease; Cough; Enalapril; Female; Humans; Middle Aged

Topics: Aged; Chronic Disease; Cough; Enalapril; Female; Humans; Middle Aged

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Chronic Disease; Enalapril; Heart Failure; Hemodynamics; Humans; Regional Blood Flow; Vascular Resistance; Vasodilator Agents

To test the hypothesis that intravenous enalapril is a useful pharmacologic probe of the renin angiotensin system, intravenous enalapril was administered to 9 patients with severe congestive heart failure (CHF). This produced abrupt and complete blockade of converting enzyme, with peak effect occurring at 30 minutes, as reflected by increases of plasma renin activity (from 16.8 +/- 6 to 86.6 +/- 23 ng/ml/hour) and decreases of plasma aldosterone levels (from 46 +/- 14 to 25 +/- 6 ng%) (both p less than 0.05). With reduction of angiotensin II--mediated vasoconstriction, systemic vascular resistance decreased markedly (from 1,974 +/- 233 to 1,400 +/- 136 dyne s cm-5) and cardiac index was improved (from 1.88 +/- 0.9 to 2.20 +/- 0.21 liters/min/m2) (both p less than 0.05). The time course of angiotensin II levels suggested that the lack of a cumulative effect from additive doses of intravenous enalapril was a reflection of complete inhibition of converting enzyme. One patient did not respond to enalapril; despite comparable hemodynamic severity of CHF, the renin-angiotensin system was not activated in this patient. Thus, intravenous enalapril is capable of rapid and complete inhibition of converting enzyme for the accurate assessment of angiotensin II--mediated vasoconstriction in patients with severe CHF.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Dipeptides; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Renin-Angiotensin System

To define the short-term haemodynamic, hormonal and electrolyte effects of enalapril in chronic heart failure, we administered it to nine patients. The first dose (5 mg) induced a gradual reduction in plasma angiotensin II, systemic vascular resistance, arterial pressure, heart rate and right heart pressures, the maximum effects occurring within 4-8 h. Angiotensin II levels were still suppressed 24 h after the initial dose, but haemodynamic indices had returned almost to control values by this time. Dose-related increases in cardiac index and plasma renin, and decreases in angiotensin II, systemic vascular resistance and urine aldosterone excretion were seen with 5, 10 and 20 mg enalapril. Cumulative balances for sodium and potassium were positive, plasma potassium increased and plasma antidiuretic hormone fell. After 4-8 weeks of enalapril therapy, clinical status and exercise tolerance improved in the patients who were most severely restricted initially. Enalapril may be useful in the treatment of chronic heart failure.

Topics: Aged; Aldosterone; Angiotensin II; Blood Pressure; Chronic Disease; Electrolytes; Enalapril; Female; Furosemide; Heart Failure; Heart Rate; Hemodynamics; Humans; Kinetics; Male; Middle Aged; Renin; Vascular Resistance

Converting enzyme inhibition of the renin-angiotensin system has proved a valuable therapeutic approach in patients with severe chronic congestive heart failure. In the present study, a new long-acting converting enzyme inhibitor (enalapril) was evaluated with acute single dose testing (10, 20 or 40 mg) in nine patients with severe chronic congestive heart failure. Four hours after administration, there was a significant reduction of systemic vascular resistance (-19%) and pulmonary wedge pressure (-19%); in addition, there were related increases of cardiac index (+16%) and stroke index (+19%) (probability [p] less than or equal to 0.05 for all changes). This was associated with an increase of plasma renin activity (9 +/- 3 to 35 +/- 11 ng/ml per hour) and a decrease of plasma aldosterone (19 +/- 4 to 9 +/- 2 ng/100 ml) (p less than 0.02 for both). With long-term therapy (1 month), there was improvement of exercise tolerance time and lessening of symptoms based on the New York Heart Association classification. Hemodynamic improvement was maintained in most, but not all, patients. There was no orthostatic hypotension during head-up tilt and hemodynamic values in the upright position were associated with normalization of intracardiac pressures. Long-term converting enzyme inhibition was indicated by a persistent increase of plasma renin activity (16 +/- 2 ng/ml per hour) and a decrease of plasma aldosterone (8 +/- 3 ng/100 ml). In addition, relative angiotensin II receptor occupancy was decreased as judged by the pharmacodynamic response to infusion of the angiotensin II analog saralasin. In conclusion, the long-acting converting enzyme inhibitor, enalapril, was effective in patients with chronic congestive heart failure; however, additional studies will be necessary to further delineate the optimal dose range and identify those patients who are most likely to respond to the drug.

Topics: Administration, Oral; Aged; Chronic Disease; Dipeptides; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Hypotension, Orthostatic; Long-Term Care; Male; Middle Aged; Oligopeptides; Saralasin; Teprotide; Time Factors