Enalapril Therapy Research Articles

The effect of IGF-1 and enalapril (ENAL) therapy on renal function and tubular apoptosis in growing rats with chronic renal failure (CRF)

The effect of IGF-1 and enalapril (ENAL) therapy on renal function and tubular apoptosis in growing rats with chronic renal failure (CRF)

ACE inhibition improves glomerular size selectivity in patients with idiopathic membranous nephropathy and persistent nephrotic syndrome

Patients with idiopathic membranous nephropathy (IMN) and persistent nephrotic-range proteinuria are at risk for progression to end-stage renal failure. Whether angiotensin-converting enzyme (ACE) inhibitors are also renoprotective in these patients remains elusive. In 14 patients with IMN (patients) and persistent proteinuria (protein > 3 g/24 h for >6 months), we studied mean arterial pressure (MAP), urinary protein excretion, glomerular filtration rate (GFR), renal plasma flow (RPF), and albumin and neutral dextran fractional clearance after 2 months washout from previous antihypertensive treatment (basal), after 2 months of enalapril (2.5 to 20 mg/d) therapy (posttreatment), and 2 months after enalapril withdrawal (recovery). MAP, proteinuria, and GFR were also measured at the same time points in 6 patients with IMN and persistent overt proteinuria maintained on conventional treatment throughout the study period (controls). Basal MAP, proteinuria, and GFR were similar in the two study groups. However, in patients at the end of the treatment period, MAP (posttreatment, 99.6 ± 11.2 versus basal, 103.3 ± 12.1 mm Hg; P < 0.05), proteinuria (posttreatment protein, 5.0 ± 2.9 versus basal, 7.1 ± 4.9 g/24 h; P < 0.05), albumin fractional clearance (posttreatment median, 1.7 × 10−3; range, 0.2 to 22.7 × 10−3 versus basal median, 4.1 × 10−3; range, 0.4 to 22.1 × 10−3; P < 0.05), and fractional clearance of largest neutral dextrans (radii from 62 to 66 Å) were significantly less than basal values. At recovery, MAP significantly increased to 106.6 ± 11.7 mm Hg (P < 0.001 versus enalapril), but all other parameters remained less than basal values. GFR and RPF were similar at each evaluation. Changes in proteinuria after treatment withdrawal positively correlated (r = 0.72; P < 0.01) with baseline GFR. Theoretical analysis of dextran-sieving data indicated that ACE inhibitor treatment significantly improved glomerular membrane size-selective dysfunction. This effect persisted more than 2 months after treatment withdrawal. No patient had symptomatic hypotension, acute renal function deterioration, or hyperkalemia during enalapril treatment. Thus, in patients with IMN and long-term nephrotic syndrome, ACE inhibitor treatment, but not conventional therapy, improves glomerular barrier size selectivity. The antiproteinuric effect of ACE inhibition is long lasting, especially in patients with more severe renal insufficiency. This is the premise of a long-term renoprotective effect that may limit the need for treatment with more toxic drugs.

Effect of high- versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure

OBJECTIVESWe 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).BACKGROUNDImmunological 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.METHODSSeventy-five patients (mean age 52 ± 11 years) with CHF were randomized between low- (5 mg 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).RESULTSAll 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.CONCLUSIONSIn 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.

Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction

OBJECTIVESWe investigated the effects of enalapril therapy on plasma tissue factor (TF), tissue factor pathway inhibitor (TFPI) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with acute myocardial infarction.BACKGROUNDMacrophages express TF in human coronary atherosclerotic plaques. Both TF and TFPI are major regulators of coagulation and thrombosis. Monocyte chemoattractant protein-1 is a monocyte and macrophage chemotactic and activating factor.METHODSIn a randomized, double-blind, placebo-controlled study beginning about two weeks after myocardial infarction, 16 patients received four weeks of placebo (placebo group) and another 16 patients received four weeks of enalapril 5 mg daily therapy (enalapril group). We performed blood sampling after administration of the doses.RESULTSThere were no significant differences in the serum angiotensin-converting enzyme (ACE) activity, plasma TF, free TFPI or MCP-1 levels before administration between the enalapril and placebo groups. In the enalapril group, ACE activity (IU/liter) (14.0 before, 5.2 on day 3, 5.8 on day 7, 6.3 on day 28), TF levels (pg/ml) (223, 203, 182, 178) and MCP-1 levels (pg/ml) (919, 789, 790, 803) significantly decreased by day 28. However, the free TFPI levels (ng/ml) (28.2, 26.5, 26.8, 28.4) did not change. These four variables were unchanged during the study period in the placebo group.CONCLUSIONSThis study demonstrated that administration of enalapril reduces the increased procoagulant activity in patients with myocardial infarction associated with inhibition of the activation and accumulation of macrophages and monocytes.

Racial differences in response to therapy for heart failure: Analysis of the vasodilator-heart failure trials

Background: Heart failure in blacks has been associated with a poorer prognosis than in whites. In such diseases as hypertension, blacks show pathophysiological differences and respond differently to some therapies than whites. The aim of this study is to evaluate the clinical characteristics and response to therapy of black compared with white patients with heart failure. Methods and Results: In the first Vasodilator-Heart Failure Trial (V-HeFT I), 180 black male patients were compared with 450 white male patients for baseline characteristics, prognosis, and response to therapy. In V-HeFT II, the same comparisons were made for 215 black and 574 white male patients, including an analysis stratified by the presence or absence of a history of hypertension. In both trials, black patients had a lower incidence of coronary artery disease, greater incidence of previous hypertension, and a greater cardiothoracic ratio ( P < .05) than white patients. In V-HeFT II, plasma norepinephrine levels were significantly less in blacks; plasma renin activity was less only in blacks with a history of hypertension. Overall mortality or hospitalization for congestive heart failure did not differ between blacks and whites in the placebo group in V-HeFT I. However, the mortality of black patients receiving hydralazine plus isosorbide dinitrate (H-I) was reduced ( P = .04) in V-HeFT I, whereas white patients showed no difference from placebo. In V-HeFT II, only white patients showed a mortality reduction from enalapril therapy compared with H-I therapy ( P = .02). Whites also showed evidence of greater blood pressure reduction and enhanced regression of cardiac size in response to enalapril. When stratified by history of hypertension in V-HeFT II, only whites with a history of hypertension, who had greater renin levels, showed significant mortality reduction with enalapril compared with H-I therapy. Hospitalization rates did not differ between treatment groups in either study. Conclusion: Whites and blacks showed differences in cause, neurohormonal stimulation, and pharmacological response in heart failure. This retrospective analysis suggests angiotensinconverting enzyme inhibitors are particularly effective in whites, and the H-I combination can be equally effective in blacks. Prospective trials involving large numbers of black patients are needed to further clarify their response to therapy.

Losartan and enalapril therapies enhance vasodilatation in the mesenteric artery of spontaneously hypertensive rats

We studied the effects of 10-week long enalapril and losartan treatments (4 and 15 mg kg −1 day −1, respectively) on mesenteric arterial function in vitro in spontaneously hypertensive rats (SHR) and Wistar–Kyoto rats (WKY). The relaxations of noradrenaline-precontracted rings to acetylcholine, nitroprusside and cromakalim were similar in WKY and enalapril- and losartan-treated SHR, and more pronounced than in untreated SHR. The responses to acetylcholine were attenuated by N G-nitro- l-arginine methyl ester in WKY and drug-treated SHR, but were completely inhibited in untreated SHR. When hyperpolarization of smooth muscle was prevented by KCl-induced precontractions, no differences were found in the relaxations to acetylcholine and nitroprusside between the groups, and the dilatations to cromakalim were abolished. Moreover, in noradrenaline-precontracted rings of drug-treated SHR, the addition of tetraethylammonium attenuated the nitric oxide synthase and cyclooxygenase-resistant relaxations to acetylcholine and abolished the enhanced dilatations to nitroprusside. In conclusion, since the enhancement of vasorelaxation in enalapril- and losartan-treated SHR was abolished by conditions preventing hyperpolarization, the improved vasodilatation following these therapies could be attributed to enhanced vasodilatation via K + channels in this model of hypertension.

The effects of an angiotensin-converting inhibitor (enalapril) on patients with mild cardiac failure--evaluating cardiac function based on the relationship between daily walking pace and heart rate.

Heart failure has been evaluated by several methods, the New York Heart Association (NYHA) classification of heart failure based on symptoms being used most frequently. However, the degree of heart failure assessed by these criteria does not always correlate with cardiac function in daily life. The aim of the study was to evaluate cardiac function based on the walking pace/heart rate (HR) relationship to assess the effects of enalapril, an angiotensin-converting enzyme inhibitor, in patients with mild to moderate cardiac function. To evaluate cardiac function objectively, we developed a method using a pedometer to count the steps walked while simultaneously recording HR using a Holter electrocardiograph (ECG). Step-count walk rate (WR) was recorded on the magnetic tape of the Holter apparatus, and both HR and walking pace were calculated automatically by the Holter ECG analysis system. Data were determined every hour, and mean pace and HR were plotted along the x and y axes, respectively. The slope of HR x WR was calculated using the least squares method. The slope and the total number of steps were regarded as indicators of cardiac function and quality of life, respectively. We analyzed 36 subjects, consisting of 8 normal volunteers, 8 patients in New York Heart Association (NYHA) class I. 11 in class II, and 9 in class III chronic mild heart failure, during maximal exercise work load by bicycle ergometer; furthermore, fractional shortening of the left ventricle on echocardiogram was determined in 14 patients with chronic mild heart failure and was compared with the slope of HR x WR. Enalapril was administered at a daily dose of 2.5-10 mg for 1-24 months (mean 6 months) in 60 patients to evaluate the effects of this drug on these parameters. There was a significant inverse relationship between maximal work load and the HR x WR slope, and also between the fractional shortening and the slope, suggesting that the slope may reflect the severity of cardiac dysfunction. Furthermore, the slope decreased significantly from 1.8 +/- 1.26 before enalapril to 1.0 +/- 0.94 (mean +/- standard deviation) after drug administration, while the total number of steps increased significantly from 4842 +/- 3581 to 7804 +/- 4793. The slope of the graph relating step count and HR proved to be a good, objective indicator of cardiac function, and enalapril therapy improved this parameter.

Effect of enalapril therapy on left ventricular mass and volumes in asymptomatic chronic, severe mitral regurgitation secondary to mitral valve prolapse

Quantitative 2-dimensional and Doppler echocardiography was used to assess the longitudinal effects of angiotensin-converting enzyme inhibition in asymptomatic patients with chronic, severe mitral regurgitation due to mitral valve prolapse. Over a 6-month period, angiotensin-converting enzyme inhibition therapy resulted in significant reductions in left ventricular volumes and mass in association with a minor reduction in regurgitant fraction.

Enalapril restores depressed circulating insulin-like growth factor 1 in patients with chronic heart failure

Background: Congestive heart failure (CHF) is characterized by increased activity of the renin-angiotensin system. Recent experimental studies have shown that infusion of angiotensin II results in depressed plasma levels of insulin-like growth factor 1 (IGF-1) and weight loss. We have previously reported that stable patients with CHF have decreased activity of the growth hormone (GH)-IGF1 axis. We have hypothesized, therefore, that angiotensin-converting enzyme (ACE) inhibition therapy should restore GH-IGF1 activity in CHF patients. Methods and Results: Nine patients with stable CHF who were taking digitalis and diuretics, New York Heart Association functional class III were studied before and after 8 weeks of therapy with Enalapril (10 mg twice daily). We measured IGF1 levels, radionuclide left ventricular ejection fraction (EF) and peak oxygen consumption (PVo 2). We found that 7 of 9 patients had abnormally low levels of IGFI (0.2–0.5 mU/ml). IGF1 levels reverted to normal after Enalapril therapy (0.36 ± 0.03 to 0.8 ± 0.14 mU/ml, P = .004). This was associated with a significant increase in EF (27.4 ± 1.1 to 31.4 ± 0.9%) and PVo 2(14.8 ± 1.2 to 18.6 ± 1.5 ml/kg/min) values ( P < .05). Conclusion: Chronic ACE inhibition therapy restored previously reduced IGF1 plasma levels in patients with CHF, most likely by reducing angiotensin II activity.

Long-Term Enalapril Therapy in Patients with Chronic Renal Failure on a Low-Protein Diet

The effect of enalapril (5–10 mg/day) on the progression of chronic renal failure (CRF) was compared with that of metoprolol (40–120 mg/day) in 28 patients for 24 months in a prospective study. Throughout the study, there was no significant difference between the 2 groups in protein intake and urinary sodium excretion. But there was a significant difference between the 2 groups in diastolic and mean arterial blood pressure at 6 months. In the serum creatinine level, there was a significant difference between the 2 groups at 6, 12, 18, and 24 months. In creatinine clearance, there was a significant difference between the 2 groups at 24 months. In addition, the progression of CRF was significantly faster in the metoprolol group than the enalapril group as estimated from the slope of creatinine clearance (p < 0.05) and the slope of glomerular filtration rate (p < 0.0005). In urinary protein excretion, there was a significant difference between the 2 groups at 6 and 18 months (p < 0.05). These findings indicate that enalapril has a suppressive effect on the progression of CRF and also has an antiproteinuric effect by a mechanism independent of its antihypertensive effect.

E006 Comparative study of doxazosin and hydrochlorothiazide when added to nonresponders to ace inhibitor enalapril therapy

E006 Comparative study of doxazosin and hydrochlorothiazide when added to nonresponders to ace inhibitor enalapril therapy

Downregulation of Endothelin B Receptors in Cardiomyopathic Hamsters

The mechanisms responsible for abnormal fluid retention in congestive heart failure (CHF) are unclear. Studies were conducted to elucidate how endothelin (ET) may contribute to salt and water retention. Cardiomyopathic (CM) hamsters with moderate heart failure were employed for in vivo and in vitro trials. Clearance methods were used to compare the level of renal function in CM hamsters and control animals. Radioligand binding studies were also performed to determine ET receptor distribution in the inner medullary collecting ducts. CM hamsters exhibited an attenuated response to ANF infusion (FE_Na: 2.7 ± 0.5 vs. 5.9 ± 0.8%, p < 0.01; FE_H2O: 1.7 ± 0.3 vs. 3.2 ± 0.4%, p < 0.01; U_cGMP: 11.2 ± 2.3 vs. 16.6 ± 2.0 pmol/min, p < 0.05) and a decrease in total ET receptor density (532 ± 77 vs. 959 ± 154 fmol/mg protein, p < 0.005). Particularly ET_B receptors were significantly reduced (214 ± 26 vs. 483 ± 88 fmol/mg protein, p < 0.003). Enalapril therapy simultaneously restored the natriuretic and diuretic effects of ANF and ET receptor density in the diseased animals. These studies suggest that the renin-angiotensin-aldosterone system and ET hormonal system act together, via ET_B receptor downregulation, to promote the abnormal fluid retention observed in CHF.

Antiplatelet Agents and Survival: A Cohort Analysis From the Studies of Left Ventricular Dysfunction (SOLVD) Trial

Objectives. This study sought to evaluate the relation between antiplatelet agent (APA) use and survival and morbidity from cardiac disease in patients with left ventricular (LV) systolic dysfunction.Background. APAs play an important role in the prevention and treatment of coronary disease. Their effects in patients with LV systolic dysfunction are unknown.Methods. We reviewed data on APA use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between their use and all-cause mortality as well as the combined end point of death or hospital admission for heart failure (HF). We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between APA use and selected patient variables in relation to outcome.Results. APA use (46.3% of patients) was associated with significantly reduced mortality from all causes (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.73 to 0.92, p = 0.0005) and reduced risk of death or hospital admission for HF (adjusted HR 0.81, 95% CI 0.74 to 0.89, p < 0.0001) but was not influenced by trial assignment, gender, LV ejection fraction, New York Heart Association class or etiology. A strong interaction was observed among APA use, randomization group and all-cause mortality. The association between APA use and survival was not observed in the enalapril group, nor was an enalapril benefit on survival detectable in patients receiving APAs at baseline. However, randomization to enalapril therapy significantly reduced the combined end point of death or hospital admission for HF in APA users.Conclusions. In patients with LV systolic dysfunction, use of APAs is associated with improved survival and reduced morbidity. This association is retained after adjustment for baseline characteristics. APA use is associated with retained but reduced benefit from enalapril.

Enalapril‐induced anemia in a renal transplant patient

Side-effects of angiotensin converting enzyme (ACE) inhibitors, such as a slight decrease in hematocrit, are increasingly being reported. A 14-year-old renal transplant patient on enalapril therapy developed anemia with reticulocytosis. She was investigated for other causes of anemia and enalapril therapy was ceased. Her hemoglobin level increased and reticulocyte count decreased after cessation of therapy. No other cause of anemia was found. Although anemia in patients receiving ACE inhibitors such as enalapril has previously been reported, this is the first reported patient who developed anemia associated with mild reticulocytosis and macrocytosis.

Incidence of cough induced by imidapril in patients with hypertension with enalapril-associated cough

The purpose of this study was to determine the incidence of cough and changes in blood levels of prostaglandin after replacement with imidapril in patients with hypertension with a history of enalapril-induced cough. In 18 patients (3 men and 15 women), enalapril decreased mean aortic blood pressure statistically significantly from 124 ± 14 mm Hg to 104 ± 12 mm Hg. Enalapril had to be withdrawn because of the development of irritating dry cough during this therapy. After verifying that the cough had disappeared following withdrawal of enalapril, we began medication with imidapril 5 mg in 15 (83%) of the 18 patients (1 patient had gastrointestinal irritation and 2 were lost to follow-up), resulting in a statistically significant decrease in mean aortic blood pressure from 128 ± 16 mm Hg to 108 ± 10 mm Hg. The cough profile during imidapril therapy was compared with that during enalapril therapy. During the follow-up period (31 ± 13 weeks), 5 patients (group 1, mean age 61 ± 17 years; 5 women) had to stop taking imidapril because irritating cough, 6 patients had no cough (group 2, mean age 63 ± 12 years; 1 man, 5 women), and 4 patients who had a dry cough less severe than that during enalapril therapy but that did not preclude their continuing use of imidapril (group 3, mean age 69 ± 12 years; 2 men, 2 women). Imidapril had no effect on the plasma concentration of either prostaglandin F 2α or thromboxane B 2 in any group, but the prostaglandin E 2 concentrations showed a statistically significant increase in groups 2 and 3. Sulindac, a prostaglandin synthesis inhibitor, was administered to 3 patients in group 1 and 2 patients in group 3 selected at random. Sulindac abolished the cough completely in 4 patients and was partially effective in 1 patient. Imidapril could be used in 67% (groups 2 and 3) of patients with enalapril-induced cough. We conclude that local, not systemic, activation of the prostaglandin cascade is responsible for the development of this side effect of angiotensin-converting enzyme (ACE) inhibitors. Although this was an uncontrolled, open-label study, our results provide a potential new treatment with imidapril for patients with hypertension when ACE inhibitors are indicated but cough develops with

Effect of enalapril therapy on glomerular accumulation of immune complexes and mesangial matrix in experimental glomerulonephritis in the nonhuman primate

The present study is a prospective, controlled, blinded trial of enalapril therapy in experimental immune complex (IC)-mediated glomerulonephritis (GN) in the nonhuman primate (cynomolgus monkey [CYn]). Two groups of CYNs were studied: those with established GN (study A) and those in which GN was being induced (study B). In study A, 12 CYNs had GN established by 8 or 10 weeks of daily intravenous infusion of bovine gamma-globulin (BGG). These CYNs were then assigned to either 4 weeks of daily oral enalapril therapy (n = 6) or daily oral placebo therapy (n = 6). The daily BGG infusions were continued during the 4 weeks of enalapril or placebo therapy. At the start of the enalapril/placebo protocol, the two groups were similar with respect to proteinuria and level of precipitating antibody to BGG, which determined the daily BGG dose. Renal biopsy was performed in each CYN at the start and end of the 4-week period of enalapril/placebo protocol. In study 13, 15 normal CYNs were immunized to BGG over a period of 4 weeks. The CYNs were then assigned to daily oral enalapril therapy (n = 8) or placebo therapy (n = 7) based on level of precipitating antibody to BGG. At this point, daily intravenous BGG was begun along with daily enalapril or placebo for 8 weeks. Renal biopsy was performed in each CYN before and at the end of this 8-week period. In study A, enalapril therapy was associated with a significant decrease in mesangial matrix volume (mean change, −27.7%; P = 0.031) and a trend toward decreased mesangial matrix deposits (mean change, −34.1%; P = 0.188). By contrast, in CYNs receiving placebo therapy, mesangial matrix volume increased compared with the enalapril group ( P = 0.002) and mesangial deposits were unchanged. In study B, both the enalapril and placebo groups showed significant increases in mesangial matrix volume, mesangial deposits, mesangial cell volume, and capillary wall deposits during the 8 weeks of daily BGG infusion. However, none of the differences between the groups achieved statistical significance. Changes in mesangial cell volume and capillary wall deposits were also evaluated in study A and study B, but were not found to be different between the enalapril and placebo groups. In both study A and study B, blood pressure was lower in the enalapril groups. In conclusion, in the initial phase of IC-GN induction (0 to 8 weeks), enalapril therapy does not significantly influence the glomerular accumulation of mesangial matrix or immune deposits. However, in established IC-GN (after 8 weeks of GN induction), enalapril therapy significantly decreases the further accumulation of mesangial matrix and may decrease the further accumulation of mesangial deposits. Whether this benefit of enalapril therapy was related to lower blood pressure or to other effects of angiotensin-converting enzyme (ACE) inhibition was not determined in this study.

Improvement in endothelial function by angiotensin converting enzyme inhibition in insulin-dependent diabetes mellitus.

We postulated that nitric oxide (NO)-mediated endothelial function would be improved by acute and short-term treatment with an angiotensin converting enzyme (ACE) inhibitor in patients with type I diabetes mellitus, in whom endothelial function is depressed. Nine type I diabetic patients and eight healthy subjects underwent forearm blood flow measurement using strain gauge plethysmography during intraarterial infusion of incremental doses of endothelium-dependent (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside [SNP]) vasodilators. Pretreatment ACh responses were depressed in diabetic patients relative to the normal subjects (P < 0.05). No difference between the groups was evident in response to SNP. Acute ACE inhibition (with intrabrachial enalaprilat) enhanced ACh responses in the diabetic patients (P < 0.005), with a further improvement evident after 1 mo of oral therapy with enalapril (P < 0.001) when ACh responses were normalized. ACE inhibition did not affect SNP responses. We conclude that acute administration of the ACE inhibitor, enalaprilat, enhances NO-mediated endothelial function in type I diabetic patients, with further improvement evident after 4 wk of enalapril therapy.

Factors affecting the therapeutic response of enalapril in treatment of post transplant erythrocytosis

Summary: Enalapril was used for post transplant erythrocytosis (PTE) in 19 stable male hypertensive renal allograft recipients. Post transplant erythrocytosis was defined as haematocrit (Hct) &gt;0.45 for 3 consecutive months. Dosage of enalapril was adjusted according to the blood pressure of individual patients and varied from 2.5 mg to 20 mg per day in divided doses. Patients’serum creatinine level, blood pressure and haematocrit were monitored. Therapeutic response was expressed as percentage drop in Hct (Δ%Hct). Factors affecting Δ%Hct was then determined. After 32 weeks of treatment, haematocrit fell from 0.495 ± 0.021 to 0.396 ± 0.053, which represented a 19.9% drop (paired Student's t‐test, P &gt; 0.001). With multiple regression analysis, reciprocal of plasma creatinine (RCr) prior to enalapril therapy (B = 3.40 ± 0.72, P &gt; 0.0005), dose of enalapril adjusted with bodyweight (B = ‐ 0.058 ± 0.020, P &gt; 0.02, and pre‐treatment haematocrit level (B = ‐ 1.90 ± 0.71, P &gt; 0.02) were found to be independent factors affecting Δ%Hct. We concluded that the dosage of enalapril, renal allograft function and severity of erythrocytosis were the major factors affecting the therapeutic response of PTE by enalapril treatment.

Fosinopril. A review of its pharmacology and clinical efficacy in the management of heart failure.

Fosinopril is the prodrug of the active diacid ACE inhibitor fosinoprilat. In patients with heart failure, fosinopril reduces pulmonary capillary wedge pressure, mean arterial blood pressure, mean right atrial pressure and heart rate, and increases stroke volume index and cardiac index. The drug has compensatory dual elimination routes via renal and hepatic systems and accumulates to a lesser extent than enalapril and lisinopril in patients with chronic renal insufficiency with or without heart failure. Comparative studies of 3 or 6 months' duration with fosinopril 10 to 40 mg/day have demonstrated clinical efficacy significantly superior to that of placebo in patients with heart failure [mostly New York Heart Association (NYHA) functional class II or III]. Fosinopril treatment consistently increased exercise duration and improved heart failure symptoms in these patients. Significantly fewer fosinopril than placebo recipients withdrew or were hospitalised because of worsening heart failure. Additionally, significantly more fosinopril than placebo recipients showed improvement, and fewer patients had deteriorated, in terms of NYHA functional class. Fosinopril and enalapril showed similar clinical efficacy over 6 and 12 months' treatment in patients with NYHA functional class II to IV heart failure. As yet, there are no data showing a mortality benefit with fosinopril. Fosinopril was well tolerated in clinical trials in patients with heart failure. Dizziness (11.9 vs 5.4% for placebo), cough (9.7 vs 5.1%) and hypotension (4.4 vs 0.8%) were the most commonly reported adverse events. In 6- or 12-month comparative studies, fosinopril therapy was associated with a lower incidence of dizziness and hypotension, but a higher incidence of vertigo, than enalapril therapy. 0.8% of patients discontinued the drug because of cough, which occurred to a similar extent with fosinopril and enalapril. Thus, based on available clinical evidence, fosinopril is an effective and well tolerated option for the management of patients with heart failure. Although clinical data are limited, fosinopril may be especially useful in patients with renal or hepatic impairment.

Effects of enalapril on left ventricular function and exercise performance after a first acute myocardial infarction

Aims: To study the effects of early use of enalapril on left ventricular function and exercise capacity after a first acute myocardial infarction, 356 patients without overt signs of congestive heart failure were randomly allocated to receive placebo or enalapril between days 7 and 14 after a first myocardial infarction. The study was conducted double-blind in 40 hospitals throughout Spain. Methods and results: At baseline and after 26 weeks of follow-up exercise stress tests, Doppler-echocardiograms and isotopic ventriculography were performed in study participants. At the end of follow-up, patients in the enalapril group had lower end-systolic volume compared to those in the placebo group (55 vs. 62 ml; P=0.05). No difference in exercise capacity was evident between both groups. Conclusion: The present study shows that enalapril therapy administered between 7 and 14 days after a first acute myocardial infarction decreases end-systolic volume and may inhibit the remodeling process of the left ventricle.