enalapril and Anemia

A 35-year-old renal transplant patient with stable renal function developed an unexplained anaemia. Appropriate investigations proved non-diagnostic. Only when enalapril therapy was stopped did the anaemia reverse and haemoglobin levels returned to pre-treatment levels. An association between angiotensin-converting enzyme inhibitors and anaemia in patients with renal failure is becoming more evident. A literature review of this problem and its possible pathogenesis in patients with renal failure is given.

Topics: Adult; Anemia; Combined Modality Therapy; Drug Therapy, Combination; Enalapril; Glomerulonephritis, Membranoproliferative; Humans; Hypertension; Immunosuppressive Agents; Kidney Transplantation; Male; Nephrotic Syndrome; Postoperative Complications

Anemia is common in patients with heart failure with reduced ejection fraction and is associated with poor clinical outcomes. Renin-angiotensin system blockers lower hemoglobin and may induce anemia.. The authors investigated whether concomitant neprilysin inhibition might ameliorate this effect of renin-angiotensin system blockers in PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure).. Anemia was defined as hemoglobin <120 g/L in women and <130 g/L in men at screening. The authors investigated the effect of randomized treatment on clinical outcomes according to anemia status, change in hemoglobin from baseline, and the incidence of anemia.. Of 8,239 participants with a baseline hemoglobin measurement, 1,677 (20.4%) were anemic. Patients with anemia had a more severe heart failure profile, worse kidney function, greater neurohormonal derangement, and worse clinical outcomes. Sacubitril/valsartan, compared with enalapril, decreased the risk of cardiovascular death or heart failure hospitalization similarly in patients with (HR: 0.84; 95% CI: 0.71-1.00) and without anemia (HR: 0.78 [95% CI: 0.71-0.87]; P value for interaction = 0.478). Between baseline and 12 months, hemoglobin decreased by 1.5 g/L (95% CI: 1.2-1.7 g/L) with sacubitril/valsartan compared with 2.3 g/L (95% CI: 2.0-2.6 g/L) with enalapril: mean difference 0.8 g/L (95% CI: 0.5-1.2 g/L; P < 0.001). Patients assigned to sacubitril/valsartan were less likely to develop anemia at 12 months (321 of 2,806 [11.4%]) compared with patients randomized to enalapril (440 of 2,824 [15.6%]) (OR: 0.70 [95% CI: 0.60-0.81]; P < 0.001). These findings were similar in PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) (sacubitril/valsartan vs valsartan). There was biomarker evidence of increased iron utilization with sacubitril/valsartan.. Irrespective of anemia status, sacubitril/valsartan compared with enalapril, decreased mortality and hospitalization. Hemoglobin decreased less with sacubitril/valsartan and the incidence of new anemia was lower with sacubitril/valsartan. (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure [PARADIGM-HF] trial; NCT01035255).

Topics: Aminobutyrates; Anemia; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Drug Combinations; Enalapril; Female; Heart Failure; Humans; Male; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan

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

Anemia is common in patients with congestive heart failure (CHF), although its etiology and pathophysiology remain largely unexplained. The purpose of this study was to examine the prognostic significance of a low hematocrit (Hct) in patients with CHF and the possible role of angiotensin-converting enzyme inhibition in anemia development.. Hct was measured at the time of enrollment of 160 patients with CHF, mean age 56 +/- 12 years, in New York Heart Association (NYHA) functional class 2.6 +/- 0.7 and with left ventricular ejection fraction of 20 +/- 9%. They were randomized to standard (mean: 17.9 +/- 4.3 mg/day) or high (mean: 42 +/- 19.3 mg/day) doses of enalapril. The follow-up duration was 2 years. Cox regression models were used to identify prognostic factors, and correlations among individual variables were tested.. Mean baseline Hct was 42.7 +/- 5%. In multivariate analyses, low Hct (p = 0.036), older age (p = 0.022) and low systolic blood pressure (p = 0.032) were independent predictors of death within 2 years. A correlation was found between baseline Hct and NYHA class (Spearman's correlation coefficient: -0.183, p = 0.008). A significant decrease in Hct from 43.2 +/- 4.9% at baseline to 40.7 +/- 4.4% at 2 years was observed in the group treated with high doses of enalapril (p < 0.001).. Low baseline Hct predicted poor 2-year prognosis in patients with CHF. Enalapril administered in high doses increased the incidence of anemia in this population. The underlying pathophysiologic mechanism and effects of maintaining a normal Hct on clinical outcomes remain to be determined.

Topics: Adult; Aged; Anemia; Enalapril; Female; Heart Failure; Hematocrit; Humans; Male; Middle Aged; Prevalence; Prognosis

Angiotensin-converting enzyme (ACE) inhibitors, which are frequently administered in patients with heart disease, have a known inhibitory effect on erythropoiesis. The aim of this study was to detect whether early ACE inhibitor administration slows recovery from anemia following recent cardiac surgery.. Forty male patients with anemia (hemoglobin < 12 g/dL) an average of 9 days after cardiac surgery were randomized to receive enalapril (ACE inhibitor group) or not. All of the patients received ferrous sulfate, 525 mg, in addition to standard therapy. Patients with anemia due to other causes were excluded. Blood samples were obtained at baseline, and after 8 days, 16 days, and 60 days. A 6-min walking test and echocardioscan were performed at baseline, and after 16 days and 60 days of treatment, and a chest radiograph was obtained at baseline and after 60 days. The ACE inhibitor group showed a statistically significant lower increase in hemoglobin and RBC values. The peak between-group differences of 1 g/dL of hemoglobin (p = 0.012) and 444 RBCs per milliliter (p = 0.017) were observed on day 16.. Early enalapril maleate administration in anemic patients after heart surgery significantly inhibits erythropoiesis. This unfavorable effect on anemia should be considered when prescribing ACE inhibitors for such patients.

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Cardiac Surgical Procedures; Enalapril; Erythropoiesis; Hemoglobins; Humans; Male; Middle Aged; Postoperative Period; Stroke Volume

Anemia has been frequently reported in renal transplant recipients receiving azathioprine for immunosuppression and enalapril for treatment of hypertension. During the course of a prospective trial in such patients we determined azathioprine metabolites in erythrocytes, plasma, and urine as well as erythropoietin and hemoglobin levels in order to evaluate a potential interaction between these 2 drugs, possibly leading to anemia. Two specific high performance liquid chromatography (HPLC) methods for determination of azathioprine metabolites, both employing a mercurial cellulose resin for extraction, are presented. One method using a strong anion exchange column allows detection of 6-thioguanosine di- and triphosphate (thioguanine nucleotides) in red blood cells (RBC) with a sensitivity of 30 pmol/100 microliters RBC. 6-mercaptopurine (MP) and 6-thiouric acid (TUA) in plasma and urine were analyzed simultaneously by reversed-phase HPLC with a sensitivity of 5 ng/ml. The average (median values are given) steady state concentrations of thioguanine nucleotides in erythrocytes came to 267 pmol/100 microliters RBC (range 53-613) with and to 246 pmol/100 microliters RBC (range 39-629) without concomitant enalapril medication. Mean plasma concentrations of MP and TUA 3 hours after drug intake came to 14.8 +/- 9.9 ng/ml and 398 +/- 262 ng/ml, respectively, during enalapril comedication. Withdrawal of enalapril did not influence these metabolite levels coming to 15.3 +/- 9.1 and 451 +/- 253 after stopping enalapril treatment. Thioguanine nucleotides in RBCs were neither related to the dose of azathioprine given (r = -0.113, p > 0.05) nor to hemoglobin levels (r = 0.278, p > 0.05). However, azathioprine dose/kg body weight seemed to be related to hemoglobin concentration, with and without enalapril comedication. We conclude that enalapril therapy does not influence the measured azathioprine metabolites, the reported cases of anemia may rather be due to a pharmacodynamic interaction as shown by the significant increase in erythropoietin after withdrawal of enalapril. The assays described here are suitable to study the metabolism of azathioprine in patients with various diseases.

Topics: Administration, Oral; Anemia; Antihypertensive Agents; Azathioprine; Drug Interactions; Enalapril; Erythrocytes; Hemoglobins; Humans; Immunosuppressive Agents; Kidney Transplantation; Mercaptopurine; Prospective Studies; Spectrophotometry, Ultraviolet; Uric Acid

26 patients with hypertension while on hemodialysis or continuous ambulatory peritoneal dialysis for end-stage renal diseases were treated first with enalapril and then changed to metoprolol. Both drugs were shown to be similarly effective in controlling blood pressure. There was no difference between the two drugs in their effects on renal function, potassium balance, lipid profile, cardiac function, exercise tolerance, and quality of life. Mild worsening of anemia was observed during treatment with enalapril. No serious side effects were reported. Use of enalapril is safe in the treatment of hypertension in dialysis patients.

Topics: Adult; Anemia; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Cell Count; Blood Pressure; Electrocardiography; Enalapril; Exercise Tolerance; Female; Humans; Hypertension; Kidney Failure, Chronic; Kidney Function Tests; Lipids; Male; Metoprolol; Middle Aged; Nifedipine; Peritoneal Dialysis, Continuous Ambulatory; Potassium; Quality of Life; Renal Dialysis

The effects of angiotensin converting enzyme (ACE) inhibitors and their combined use with an antiestrogenic steroid on erythropoiesis were investigated in patients on chronic hemodialysis (CHD). Hematocrit was decreased by 10% or more in 6 of 12 patients who received either captopril or enalapril for 2-6 months. Erythropoietin (Epo) and angiotensin II (AII) were significantly reduced in these patients. When treatment with mepitiostane was combined with ACE inhibitor, anemia was significantly improved but without evidence of changes in circulating Epo concentrations or indices of renin-angiotensin activity. The reduction of AII and Epo formation by ACE inhibitors seems to play an important role in the worsening of anemia in patients on CHD; addition of an antiestrogenic steroid should be considered.

Topics: Androstanols; Anemia; Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Erythropoiesis; Erythropoietin; Estrogen Antagonists; Humans; Kidney Failure, Chronic; Middle Aged; Renal Dialysis; Renin-Angiotensin System

Topics: Acute Disease; Anemia; Anti-Bacterial Agents; Aortic Valve; Child; Combined Modality Therapy; Diagnosis, Differential; Drug Therapy, Combination; Enalapril; Endocarditis, Bacterial; Female; Furosemide; Granulomatosis with Polyangiitis; Heart Rupture; Humans; Immunosuppressive Agents; Mitral Valve; Oxygen Inhalation Therapy; Respiration Disorders; Rickettsia Infections; Rupture, Spontaneous; Ultrasonography; Vasculitis, Leukocytoclastic, Cutaneous

We aimed to investigate the impact of angiotensin-converting enzyme inhibitors (ACEIs) on hematocrit values in those with heart failure, and the relationship between incident anemia and mortality.. Prevalent anemia is an independent risk factor for morbidity and mortality in those with heart failure. Studies in patients with polycythemia have demonstrated that ACEIs are effective in lowering hematocrit values.. We used the Studies Of Left Ventricular Dysfunction (SOLVD) database to compare the odds of developing new anemia at one year in patients who were not anemic at entry and who were randomized to enalapril or placebo. Cox proportional hazards models were utilized to determine the impact of incident and prevalent anemia on subsequent mortality.. Enalapril increased the odds of incident anemia (hematocrit < or =39% in men or < or =36% in women) at one year by 48% (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.20 to 1.82) in unadjusted and 56% (OR 1.56, 95% CI 1.26 to 1.93) in adjusted models. With multivariate analysis, prevalent anemia at randomization was associated with a 44% (hazard ratio [HR] 1.44, 95% CI 1.31 to 1.66) increase in all-cause mortality, whereas incident anemia after randomization was associated with a 108% increase (HR 2.08, 95% CI 1.82 to 2.38). After adjusting for incident and prevalent anemia, use of enalapril was associated with a survival benefit.. Enalapril was associated with increased odds of developing anemia at one year. Those with periods of time with incident anemia had the poorest survival, followed by those with prevalent anemia, then those without anemia. Enalapril was protective of overall mortality after adjusting for incident anemia and in those with prevalent anemia.

Topics: Aged; Anemia; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Follow-Up Studies; Hematocrit; Humans; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Treatment Outcome; Ventricular Dysfunction, Left

To estimate the independent effects of kidney disease, anemia, and the treatment effects of angiotensin-converting enzyme (ACE) inhibitors on hospitalization cost in patients with heart failure, we used data from the prevention and treatment trials of the Studies of Left Ventricular Dysfunction trial and retrospectively estimated the relative effects of decreased kidney function, as measured by estimated glomerular filtration rate (GFR) at enrollment, and anemia, as measured by hematocrit levels at enrollment, on hospital utilization and expense. Independent of the effects of age, gender, New York Heart Association (NYHA) class, ejection fraction, and the presence of diabetes mellitus, GFR was significantly related to hospitalization expense (percent change in hospitalization expense -16.8%, 95% confidence interval [CI] -11.9% to -21.5%) for GFR >/=90 ml/min/1.73 m(2) compared with GFR <60 ml/min/1.73 m(2)). Similarly, hematocrit levels were significantly related to hospitalization expense (percent change in hospitalization expense -19.9%, 95% CI -10.2% to -28.6%) for hematocrit >/=36% compared with hematocrit <33%). The beneficial effect of the ACE inhibitor enalapril was significantly related to hospitalization expense independent of the effects of GFR and hematocrit (percent change in hospitalization expense -6.8%, 95% CI -3.6% to -9.9% for treatment vs the placebo group), and the beneficial effect was preserved when independently estimated for subgroups with decreased kidney function. Adjusted mean expense per patient per month (PPPM) in the enalapril group was $708 versus $792 in the placebo group. Comparing survivors, enalapril generated annual cost savings greater than the average wholesale price of the drug at Studies of Left Ventricular Dysfunction mean dosage levels. Adjusted expected hospitalization expense varied from $636 PPPM for patients in the lowest hematocrit-GFR risk class (hematocrit >/=36%, GFR >/=90 ml/min/1.73 m(2)) to $1,127 PPPM for those in the highest risk class (hematocrit <33%, GFR <60 ml/min/1.73 m(2)). For patients who survived with reduced kidney function and anemia, ACE inhibitor therapy with enalapril reduced hospitalization expense more than the additional expense of the drug therapy. Thus, kidney disease and anemia are independent risk factors for hospitalization cost in patients with heart failure, and the beneficial effect of ACE inhibitors on hospitalization expense appears to be preserved within kidney disease and a

Topics: Aged; Anemia; Angiotensin-Converting Enzyme Inhibitors; Chi-Square Distribution; Enalapril; Female; Glomerular Filtration Rate; Hospital Costs; Hospitalization; Humans; Kidney Failure, Chronic; Male; Middle Aged; Randomized Controlled Trials as Topic; Regression Analysis; Retrospective Studies; Risk Factors; Ventricular Dysfunction, Left

Topics: Aged; Anemia; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Erythropoietin; Humans; Male

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Child; Enalapril; Erythropoietin; Female; Humans; Nephrotic Syndrome

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.

Topics: Adolescent; Anemia; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Kidney Transplantation; Postoperative Complications

Topics: Adult; Anemia; Angiotensin-Converting Enzyme Inhibitors; Azathioprine; Drug Therapy, Combination; Enalapril; Erythropoietin; Female; Humans; Hypertension; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Nephrotic Syndrome; Recombinant Proteins; Reoperation; Tissue Donors

Immunosuppression of recipients of renal transplants with azathioprine has been associated with two major side effects: hepatotoxicity and myelotoxicity, mainly in the form of leukopenia. Reports of isolated anemia in these patients have been rare. We now observed the development of severe anemia in 9 out of 11 renal transplant recipients whose immunosuppressive regimen was converted from cyclosporine plus prednisone to azathioprine plus prednisone. A significant (P = 0.001) drop in hematocrit (from 34 +/- 4% to 27 +/- 3%, mean +/- SD) and hemoglobin (from 11.6 +/- 1.3 g/dl to 9.5 +/- 1.0 g/dl) was found. Since a common variable of all these patients was their use of an angiotensin-converting enzyme (ACE) inhibitor as antihypertensive medication, we speculated that the combination of azathioprine and ACE blocker might be the reason for the anemia. We then compared 2 groups of 10 patients each who had been on azathioprine as their regular immunosuppressive agent and who did or did not take an ACE inhibitor. Hematocrit and hemoglobin were significantly (P = 0.01) lower in the group of patients taking ACE inhibitors (33 +/- 6% versus 41 +/- 5% and 11.5 +/- 2.0 g/dl versus 14.0 +/- 1.6 g/dl, respectively). Haptoglobin levels were also significantly (P = 0.05) lower in the ACE inhibitor group (116 +/- 65 mg/dl versus 210 +/- 114 mg/dl). Erythropoietin concentration in the serum and the reticulocyte index were slightly, but not significantly, higher in the ACE inhibitor group but the values were probably too low for their degree of anemia. Comparing hematological parameters of the patients in the ACE inhibitor group before and after beginning of the antihypertensive treatment confirmed a significant reduction of hematocrit and hemoglobin following therapy with an ACE inhibitor. Hematocrit fell from 41 +/- 7% to 36 +/- 6% and hemoglobin from 14.0 +/- 2.3 g/dl to 11.3 +/- 1.5 g/dl (P < 0.05 for both). We conclude that the combination of these two drugs should probably be avoided.

Topics: Adult; Anemia; Angiotensin-Converting Enzyme Inhibitors; Azathioprine; Enalapril; Female; Hematocrit; Hemoglobins; Humans; Hypertension; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Retrospective Studies

Two renal transplant patients developed anemia during treatment of hypertension with enalapril medication. Hemoglobin levels normalized after administration of enalapril was stopped. In one patient, it was demonstrated that the discontinuation of enalapril was followed by a decrease in renal blood flow and a significant increase in the plasma erythropoietin levels that preceded the rise in hemoglobin. These observations are consistent with the hypothesis that angiotensin-converting enzyme inhibition may cause anemia by increasing renal blood flow and consequently decreasing erythropoietin levels.

Topics: Adult; Anemia; Enalapril; Erythropoietin; Female; Humans; Hypertension; Kidney Transplantation; Male; Renal Circulation

Topics: Anemia; Enalapril; Glomerulonephritis, IGA; Humans; Hypertension; Male; Middle Aged

Topics: Aldosterone; Anemia; Blood Pressure; Enalapril; Erythropoietin; Hematocrit; Humans; Hypertension; Kidney Failure, Chronic; Kidney Neoplasms; Male; Middle Aged; Polycystic Kidney Diseases; Renal Dialysis; Renin-Angiotensin System

We encountered a renal transplant recipient who developed an unexplained 0.09 decrease in hematocrit value while taking enalapril for hypertension, which reversed when the drug was stopped. This experience, and a previous similar case report, prompted a review of all our 27 transplant patients treated with enalapril. Of these, 10 patients (37%) had developed an otherwise unaccounted for anemia: the pre-enalapril hematocrit value was 0.42 +/- 0.01 and it decreased to the nadir value of 0.33 +/- 0.01 (P less than 0.001) within 12.3 +/- 0.9 weeks after initiation of 9 +/- 2.4 mg of enalapril daily; enalapril was stopped in seven patients and their anemia resolved within 9.1 +/- 0.7 weeks to a final hematocrit value of 0.40 +/- 0.01. The remaining three patients were maintained on enalapril at their physicians' discretion, without further decrease in hematocrit values. No appreciable changes in drug regimens, clinical course, or other laboratory parameters were noted during this period. A causal relationship between enalapril and anemia was suggested by the effect of drug withdrawal and rechallenge on hematocrit in one of the patients. There were no statistically significant differences in baseline clinical and laboratory characteristics between those patients who did (group I) and those who did not (group II) develop enalapril-associated anemia, with the exception of a normal hematocrit value of 0.42 +/- 0.01 in group I versus a lower hematocrit value of 0.36 +/- 0.02 in group II (P less than 0.05). We conclude that enalapril should be considered in the differential diagnosis of anemia following renal transplantation. Susceptibility to this effect might emanate from the immunosuppressed state.

Topics: Adult; Aged; Anemia; Enalapril; Female; Hematocrit; Humans; Hypertension; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Retrospective Studies

The renin-angiotensin system has been shown to have an effect on erythropoietin synthesis and hemoglobin concentration. We present a retrospective study of stable renal transplant recipients who received an angiotensin-converting enzyme (ACE) inhibitor as treatment of hypertension. Fifteen patients were eligible, with a mean hemoglobin concentration of 130.7 +/- 22.7 g/L (SD). Within 6 months of ACE-inhibitor therapy, the mean hemoglobin had fallen significantly to 110.5 +/- 23.2 g/L (p less than 0.001). No parallel change in leukocyte or platelet counts was evident. Prospective studies are needed to clarify the effect of inhibition of the renin-angiotensin system on erythropoietin synthesis and release.

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Hemoglobins; Humans; Hypertension; Kidney Transplantation; Leukocyte Count; Platelet Count

Topics: Aged; Anemia; Captopril; Enalapril; Female; Humans; Middle Aged

Topics: Adult; Anemia; Enalapril; Hemoglobins; Humans; Hypertension; Male