enalapril and Hyperkalemia

Heart failure affects ≈5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the US Food and Drug Administration approved the first of a new class of drugs for the treatment of heart failure: Valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses 2 of the pathophysiological mechanisms of heart failure: activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared with enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacological properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension.

Topics: Abnormalities, Drug-Induced; Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Biphenyl Compounds; Bradykinin; Contraindications; Drug Combinations; Drug Costs; Drug Synergism; Enalapril; Enzyme Inhibitors; Female; Follow-Up Studies; Heart Failure; Humans; Hyperkalemia; Hypertension; Kidney; Multicenter Studies as Topic; Natriuretic Peptides; Neprilysin; Pregnancy; Prodrugs; Prospective Studies; Pyridines; Randomized Controlled Trials as Topic; Stroke Volume; Tetrazoles; Thiazepines; Valsartan

This report reviews the tolerability profile of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, in the treatment of patients with congestive heart failure. Data have been collected from 546 patients treated with enalapril for up to 9 months in clinical trials other than the Cooperative North Scandinavian Enalapril Survival Study. Results in patients treated with enalapril (n = 193) or placebo (n = 195) in double-blind, controlled clinical trials show that the incidences of death, serious adverse experiences, and adverse experiences requiring discontinuation of double-blind therapy, as well as the overall incidence of such experiences, were similar in the 2 groups. However, certain adverse experiences that are related to the mechanism of action of ACE inhibitors were seen more often after enalapril than after placebo treatment. Dizziness and hypotension were the most frequent adverse experiences reported in patients with heart failure treated with enalapril. The most frequent laboratory adverse experiences were increases in blood urea nitrogen and serum creatinine levels. hyperkalemia was also seen in patients receiving enalapril. It is possible to identify patients at risk of these experiences before initiating treatment with enalapril and to take certain measures (such as withholding or reducing the dose of diuretic drugs and discontinuing potassium supplements or potassium-sparing diuretic drugs) to reduce the likelihood that hypotension, increases in blood urea nitrogen and serum creatinine levels, or hyperkalemia will occur. Angioedema, a recognized adverse effect of ACE inhibitors, was not seen in the clinical trials reviewed here. Cough , another recognized adverse effect of these agents, was seen infrequently and rarely resulted in the discontinuation of enalapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angioedema; Blood Urea Nitrogen; Cough; Creatinine; Drug Tolerance; Enalapril; Heart Failure; Humans; Hyperkalemia; Hypotension

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Trials as Topic; Dipeptides; Enalapril; Heart Failure; Hemodynamics; Humans; Hyperkalemia; Hypotension; Proline; Renin-Angiotensin System; Risk; Time Factors; Vasodilator Agents

Consensus guidelines recommend the use of mineralocorticoid receptor antagonists (MRAs) for selected patients with symptomatic heart failure and reduced ejection fraction (HFrEF) to reduce morbidity and mortality; however, the use of MRAs in combination with other inhibitors of the renin-angiotensin-aldosterone system increases the risk of hyperkalemia.. To determine whether the risk of hyperkalemia associated with use of MRAs for patients with HFrEF is reduced by sacubitril/valsartan in comparison with enalapril.. The PARADIGM-HF (Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial randomly assigned 8399 patients with chronic HF, New York Heart Association class II to IV symptoms, and a left ventricular EF of 40% or less to treatment with enalapril 10 mg twice daily or sacubitril/valsartan 97/103 mg twice daily (previously known as LCZ696 [200 mg twice daily]) in addition to guideline-directed medical therapy. Use of MRAs was encouraged but left to the discretion of study investigators. Serum potassium level was measured at every study visit. The incidence of hyperkalemia (potassium level >5.5 mEq/L) and severe hyperkalemia (potassium level >6.0 mEq/L) among patients treated or not treated with an MRA at baseline and the risk of subsequent hyperkalemia for those newly treated with an MRA during study follow-up were defined in time-updated Cox proportional hazards models. Analyses were conducted between August 1 and October 15, 2016.. Incident hyperkalemia and severe hyperkalemia.. In comparison with the 3728 patients (44.4% of enrolled participants [21.6% female]) not taking an MRA at baseline, the 4671 patients (55.6% [22.0% female]) taking an MRA tended to be younger, with a lower EF, lower systolic blood pressure, and more advanced HF symptoms. Among those taking an MRA at baseline, the overall rates of hyperkalemia were similar between treatment groups, but severe hyperkalemia was more common in patients randomly assigned to enalapril than to sacubitril/valsartan (3.1 vs 2.2 per 100 patient-years; HR, 1.37 [95% CI, 1.06-1.76]; P = .02). In analyses including patients who newly started taking MRAs during the PARADIGM-HF trial, severe hyperkalemia remained more common in those randomly assigned to enalapril than to those randomly assigned to sacubitril/valsartan (3.3 vs 2.3 per 100 patient-years; HR, 1.43 [95% CI, 1.13-1.81]; P = .003).. Among MRA-treated patients with symptomatic HFrEF, severe hyperkalemia is more likely during treatment with enalapril than with sacubitril/valsartan. These data suggest that neprilysin inhibition attenuates the risk of hyperkalemia when MRAs are combined with other inhibitors of the renin-angiotensin-aldosterone system in patients with HF.. clinicaltrials.gov Identifier: NCT01035255.

Topics: Aged; Aminobutyrates; Biphenyl Compounds; Drug Combinations; Enalapril; Female; Heart Failure; Humans; Hyperkalemia; Incidence; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Practice Guidelines as Topic; Prospective Studies; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan

The PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) found a combination drug containing sacubitril (a neprilysin inhibitor) and valsartan (an angiotensin II receptor blocker) superior to enalapril (an angiotensin-converting enzyme inhibitor) in patients with systolic heart failure. Recently approved by the US Food and Drug Administration, sacubitril-valsartan is the first new drug in over a decade to decrease death rates in patients with systolic heart failure.

Topics: Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cardiovascular Diseases; Cough; Double-Blind Method; Drug Combinations; Enalapril; Female; Heart Failure, Systolic; Hospitalization; Humans; Hyperkalemia; Hypotension; Male; Middle Aged; Neprilysin; Renal Insufficiency; Tetrazoles; Valsartan

Previous studies have shown that the selective aldosterone blocker eplerenone, in doses of up to 200 mg/d, reduces albuminuria in patients with type 2 diabetes. This study was conducted to ascertain whether lower doses of eplerenone (50 or 100 mg/d) co-administered with the angiotensin-converting enzyme (ACE) inhibitor enalapril would produce a similar antialbuminuric effect while obviating the hyperkalemia observed previously. After open-label run-in with enalapril 20 mg/d, patients with diabetes and a urinary albumin:creatinine ratio (UACR) > or = 50 mg/g were randomly assigned to receive enalapril plus one of three double-blind daily treatments for 12 wk: placebo, eplerenone 50 mg (EPL50), or eplerenone 100 mg (EPL100). After week 4, amlodipine 2.5 to 10 mg/d was allowed for BP control (systolic/diastolic BP < or = 130/80 mmHg). The primary study end points were the percentage change from baseline at week 12 in UACR and the incidence of hyperkalemia. Secondary end points included percentage changes from baseline in UACR at weeks 4 and 8 and changes from baseline in systolic and diastolic BP. Treatment with EPL50 or EPL100 but not placebo significantly reduced albuminuria from baseline. By week 12, UACR was reduced by 7.4% in the placebo group, by 41.0% in the EPL50 group, and by 48.4% in the EPL100 group (both eplerenone groups, P < 0.001 versus placebo). The incidences of sustained and severe hyperkalemia were not significantly different in any of the three treatment arms and did not differ on the basis of quartile of estimated GFR (all NS). For the secondary end points, both eplerenone treatment groups significantly reduced albuminuria from baseline as early as week 4 (P < 0.001), whereas placebo treatment (including enalapril) did not result in any significant decreases in UACR. Systolic BP decreased significantly in all treatment groups at all time points, but, generally, all treatment groups experienced similar decreases in BP. Co-administration of EPL50 or EPL100 with an ACE inhibitor as compared with an ACE inhibitor alone significantly reduces albuminuria in patients with diabetes without producing significant increases in hyperkalemia.

Topics: Aged; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Creatinine; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Enalapril; Eplerenone; Female; Glomerular Filtration Rate; Humans; Hyperkalemia; Incidence; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Potassium; Spironolactone; Treatment Outcome; United States

To retrospectively investigate elevation of serum potassium when spironolactone (25 or 50 mg/day) and furosemide were administered concomitantly with an angiotensin II converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) to patients with chronic heart failure for 12 months and occurrence of hyperkalemia and hypokalemia because of concomitant administration of spironolactone plus an ACE-I or ARB and furosemide.. Patients with chronic heart failure, who visited departments of cardiovascular internal medicine and cardiovascular surgery at the National Hospital Organization Osaka Medical Center, were enrolled for this study. Serum potassium, blood urea nitrogen (BUN), serum creatinine, uric acid, and serum sodium were determined in every patient at the time of start of treatment and at 3 and 12 months of treatment. Data from patients in Groups A (25 mg/day spironolactone + 40 mg/day furosemide + an ACE-I or ARB) and B (50 mg/day spironolactone + 40 mg/day furosemide + an ACE-I or ARB) were analysed for differences with respect to the ACE-I and ARB used.. When 50 mg/day spironolactone plus 5 mg/day enalapril maleate (enalapril) or 50 mg/day losartan potassium (losartan) or 8 mg/day candesartan cilexetil (candesartan) plus 40 mg/day furosemide were concomitantly used, the mean value of serum potassium was significantly elevated only in the group treated with 50 mg/day spironolactone regardless of the concomitant drug. The number of patients with hyperkalemia (>5.5 mEq/L) at 12 months of treatment was 12 (8.8%), while the number of patients with hypokalemia (

Topics: Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diuretics; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Failure; Humans; Hyperkalemia; Losartan; Male; Middle Aged; Potassium; Sodium Potassium Chloride Symporter Inhibitors; Spironolactone

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have shown numerous benefits to the cardiovascular system. However, using both drugs is associated with hyperkalemia, especially in end-stage renal disease (ESRD) patients. To the authors' knowledge, there has been no prospective systematic study of the safety and potassium homeostasis of both drugs in continuous ambulatory peritoneal dialysis (CAPD) patients.. Twenty-nine stable, normokalemic CAPD patients without potassium-interference drugs were selected randomly to receive, for 4-week periods, 8 mg candesartan or 10 mg enalapril daily. After completion of the initial drug, both treatment groups were crossed.. Twenty-one patients completed the study. Baseline blood pressure, serum potassium level, plasma aldosterone, adequacy of dialysis, and residual renal function were not different between both groups. For the total group, serum potassium changes were not significantly different between baseline and at 4 weeks after treatment in both groups. The incidence of hyperkalemia (potassium > or =5.5 mEq/L [mmol/L]) was 13% and not different between groups. Nine of 11 events of hyperkalemia were associated with Kt/V urea less than 2, and 8 of 11 had low or low-average peritoneal equilibrium tests.. In ESRD patients on CAPD, the standard dose of ACE inhibitor, enalapril, or ARB, candesartan,has little effect on serum potassium, despite drops of plasma aldosterone observed. Both drugs should be considered in CAPD patients with hypertension or cardiovascular complications. However, use of both drugs requires caution in patients with inadequate dialysis or low solute transporters, and dietary noncompliant patients as well.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biphenyl Compounds; Cross-Over Studies; Enalapril; Female; Homeostasis; Humans; Hyperkalemia; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Potassium; Tetrazoles

In the Studies of Left Ventricular Dysfunction (LVD), enalapril or placebo was administered in a double-blind fashion to 6797 participants with ejection fraction < or = 0.35. During 40 months' average follow-up, 28.1% of participants randomized to enalapril reported side effects compared with 16.0% in the placebo group (p < 0.0001). Enalapril use was associated with a higher rate of symptoms related to hypotension (14.8% vs 7.1%, p < 0.0001), azotemia (3.8% vs 1.6%, p < 0.0001), cough (5.0% vs 2.0%, p < 0.0001), fatigue (5.8% vs 3.5%, p < 0.0001), hyperkalemia (1.2% vs 0.4%, p = 0.0002), and angioedema (0.4% vs 0.1%, p < 0.05). Side effects resulted in discontinuation of blinded therapy in 15.2% of the enalapril group compared with 8.6% in the placebo group (p < 0.0001). Thus enalapril is well tolerated by patients with LVD; however, hypotension, azotemia, cough, fatigue, and other side effects result in discontinuation of therapy in a significant minority of patients.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Cough; Double-Blind Method; Enalapril; Fatigue; Female; Follow-Up Studies; Heart Failure; Humans; Hyperkalemia; Hypotension; Male; Middle Aged; Sex Factors; Time Factors; Uremia; Ventricular Dysfunction, Left

During exercise a marked increase in plasma potassium in healthy subjects has repeatedly been demonstrated. In patients on treatment with angiotensin-converting enzyme inhibitors this may be further augmented. Therefore, the aim of present study was to evaluate the effect of enalapril on exercise-induced hyperkalemia. This was done in patients with acute myocardial infarction randomized to double-blind treatment with enalapril 10-20 mg per day (n = 7) or placebo (n = 6) within 24 h of onset of chest pain, and the results were compared with data from healthy control subjects (n = 11). Baseline plasma potassium did not differ between the three groups; i.e. 4.2, 4.0, and 4.1 mmol/l, respectively. An incremental, symptom-limited, bicycle exercise test was done one month after the myocardial infarction, and blood samples were taken for determination of plasma potassium. The exercise-induced increase in plasma potassium was not higher in the enalapril group as compared to the placebo and control groups, and there was no difference between the enalapril and placebo group, the specific values being 0.6 vs. 0.6 and 0.7 mmol/l, respectively. No difference was observed in the slope (dK/dt) between the 3 groups. In conclusion, enalapril at a dosage of 10-20 mg per day does not provoke any augmentation of the increase in plasma potassium during exercise.

Topics: Adult; Aged; Bias; Creatine Kinase; Double-Blind Method; Enalapril; Exercise Test; Female; Hemodynamics; Humans; Hyperkalemia; Isoenzymes; Male; Middle Aged; Myocardial Infarction; Potassium

Both angiotensin-converting enzyme (ACE) inhibitors like lisinopril and nonsteroidal anti-inflammatory drugs (NSAIDs) like indomethacin have been shown to lower urinary protein excretion in renal disease. If this effect is caused by different mechanisms of action, the combination of these agents could have an additive antiproteinuric effect. We studied the effects of lisinopril and indomethacin separately and in combination in 10 patients with the nephrotic syndrome. Proteinuria was lowered from 10.5 +/- 1.8 g/24 h in the control period to 4.5 +/- 1.1 g/24 h on indomethacin, 4.3 +/- 1.0 g/24 h on lisinopril and to 2.4 +/- 0.8 g/24 h on the combination. Glomerular filtration rate (GFR) fell on either monotherapy, but particularly on the combination of drugs. The renal hemodynamic changes suggested a preglomerular vasoconstriction by indomethacin and a postglomerular vasodilation by lisinopril. Severe hyperkalemia occurred in 3 patients on the combination therapy. We conclude that the combination of indomethacin and lisinopril has an additive antiproteinuric effect. This, as well as the more pronounced fall in GFR on the combination, may suggest that both drugs lower proteinuria by decreasing intraglomerular capillary pressure but via different mechanisms. Combining these drugs may be useful in the symptomatic treatment of nephrotic syndrome, but renal function and serum potassium should be monitored carefully.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Drug Therapy, Combination; Enalapril; Female; Glomerular Filtration Rate; Humans; Hyperkalemia; Indomethacin; Lisinopril; Male; Middle Aged; Nephrotic Syndrome

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Trials as Topic; Dipeptides; Enalapril; Heart Failure; Hemodynamics; Humans; Hyperkalemia; Hypotension; Proline; Renin-Angiotensin System; Risk; Time Factors; Vasodilator Agents

none.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Enalapril; Heart Arrest; Humans; Hyperkalemia; Male; Spironolactone

Enalapril is used to treat hypertension and congestive heart failure in infants. However, enalapril is not labeled for neonates, and safety data in infants are sparse. To evaluate the safety of enalapril in young infants, we conducted a retrospective cohort study of infants who were exposed to enalapril in the first 120 days of life and were cared for in 348 neonatal intensive care units from 1997 to 2012. We determined the proportion of exposed infants who developed adverse events, including death, hypotension requiring pressors, hyperkalemia, and elevated serum creatinine. Using multivariable logistic regression, we examined risk factors for adverse events, including postnatal age at first exposure, exposure duration, gestational age group, small for gestational age status, race, sex, 5-min Apgar score, and inborn status. Of a cohort of 887,910 infants, 662 infants (0.07%) were exposed to enalapril. Among exposed infants, 142 infants (21%) suffered an adverse event. The most common adverse event was hyperkalemia (13%), followed by elevated serum creatinine (5%), hypotension (4%), and death (0.5%). Significant risk factors for adverse events included postnatal age <30 days at first exposure and longer exposure duration. This study is the largest to date examining the safety of enalapril in young term and preterm infants without significant structural cardiac disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cohort Studies; Creatinine; Enalapril; Female; Gestational Age; Humans; Hyperkalemia; Hypotension; Infant; Infant Mortality; Infant, Newborn; Intensive Care Units, Neonatal; Logistic Models; Male; Retrospective Studies; Risk Factors

Topics: Aminobutyrates; Biphenyl Compounds; Drug Combinations; Enalapril; Heart Failure; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Tetrazoles; Valsartan

Topics: Aminobutyrates; Biphenyl Compounds; Drug Combinations; Enalapril; Heart Failure; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Neprilysin; Tetrazoles; Valsartan

To evaluate the efficacy and safety of losartan and enalapril in pediatric kidney transplant recipients.. A retrospective review was performed in 31 pediatric kidney transplant recipients who were treated with losartan (50 mg/d, oral) for 1 to 6 months because of mild hypertension and persistent proteinuria. All patients were treated concurrently with enalapril (5 or 10 mg daily, oral), and 12 patients (39%) also were treated with amlodipine (5 or 10 mg daily, oral). Demographic and clinical characteristics of the patients were reviewed.. Losartan use was associated with a significant decrease in mean systolic (before losartan was started, 123 ± 14 mm Hg; before losartan was stopped, 111 ± 10 mm Hg; P ≤ .001) and diastolic blood pressure (before losartan was started, 78 ± 11 mm Hg; before losartan was stopped, 69 ± 10 mm Hg; P ≤ .001) and urinary protein excretion (before losartan was started, 51 ± 45 mg/m2/h; before losartan was stopped, 28 ± 34 mg/m2/h; P ≤ .001). However, losartan therapy was associated with a significant mean increase in serum potassium level (before losartan was started, 4.0 ± 0.4 mmol/L; before losartan was stopped, 5.7 ± 0.5 mmol/L; P ≤ .001) and decrease in pH (before losartan was started, 7.35 ± 0.0; before losartan was stopped, 7.23 ± 0.0; P ≤ .001). Losartan was stopped because of hyperkalemia and acidosis earlier in patients who were on tacrolimus than cyclosporine immunosuppression (tacrolimus, 3 ± 1 mo; cyclosporine, 4.7 ± 0.8 mo; P ≤ .001).. Losartan and enalapril may be beneficial in pediatric kidney transplant recipients by decreasing blood pressure and proteinuria, with maintenance of stable graft function, but may be associated with serious adverse events including hyperkalemia and life-threatening acidosis.

Topics: Acidosis; Adolescent; Age Factors; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biomarkers; Blood Pressure; Child; Child, Preschool; Drug Therapy, Combination; Enalapril; Female; Humans; Hydrogen-Ion Concentration; Hyperkalemia; Hypertension; Kidney Transplantation; Losartan; Male; Potassium; Proteinuria; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Electrocardiography; Enalapril; Humans; Hyperkalemia; Hypertension; Kidney Failure, Chronic; Male; Potassium; Renal Dialysis; Sodium Bicarbonate; Sympathomimetics

Limited data are available to predict the occurrence of hyperkalemia. Risk assessment is complicated by the lack of consistency of definition between trials.. We conducted a retrospective analysis of the SOLVD to evaluate the incidence of hyperkalemia and the value of several baseline characteristics as predictors of hyperkalemia in patients with left ventricular dysfunction.. The incidence of hyperkalemia was 6.0% and 1.1% using a definition of > or = 5.5 and > or = 6.0 mmol/L, respectively. Independent predictors of hyperkalemia (> or = 5.5 mmol/L) were randomization to enalapril, baseline serum creatinine, serum potassium, New York Heart Association functional class III or IV, a history of diabetes, and atrial fibrillation (all P < .05). The use of loop diuretics was also associated with an increased risk of hyperkalemia but only in patients included in the SOLVD prevention trial. Similar results were obtained when renal function was evaluated using the estimated creatinine clearance.. The definition of hyperkalemia is important when evaluating its incidence in clinical trials. Renal dysfunction, baseline serum potassium, diabetes, atrial fibrillation, New York Heart Association functional class, and treatment with an angiotensin-converting enzyme inhibitor are factors associated with the development of hyperkalemia in patients with left ventricular dysfunction. More specifically, our results suggests that before initiating drugs that can cause hyperkalemia in patients with heart failure, a strong consideration should be given to calculate creatinine clearance and that patients with a creatinine clearance < 60 mL/min should undergo a close monitoring of their serum potassium to prevent the development of hyperkalemia.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Creatinine; Diabetes Complications; Enalapril; Female; Humans; Hyperkalemia; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Potassium; Predictive Value of Tests; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sodium Potassium Chloride Symporter Inhibitors; Ventricular Dysfunction, Left

To retrospectively investigate the effect of carvedilol and spironolactone plus furosemide, administered concomitantly with an angiotensin II converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) to patients with chronic heart failure (CHF).. Patients with CHF, who visited Departments of Cardiovascular Internal Medicine at the National Hospital Organization Osaka Medical Center, were enrolled for this study. Serum potassium, blood urea nitrogen (BUN), serum creatinine (Scr) and serum sodium were measured in every patient at the time of start of treatment and after 3 and 12 months of treatment. Data from patients in groups A (20 mg/day carvedilol + 25 mg/day spironolactone + 40 mg/day furosemide + an ACE-I) and B (20 mg/day carvedilol + 25 mg/day spironolactone + 40 mg/day furosemide + ARB) were compared.. When 20 mg/day carvedilol plus 25 mg/day spironolactone plus 5 mg/day enalapril maleate (enalapril, group A) or 8 mg/day candesartan cilexetil (candesartan, group B) plus 40 mg/day furosemide were used concomitantly, the mean serum potassium increased significantly in both groups of patients. Seven of 59 (11.9%) patients had hyperkalemia (>5.5 mEq/L) during 12 months of treatment whereas 8.5% of patients (five of 59) had hypokalemia (< or =3.5 mEq/L).. When carvedilol is used concomitantly with spironolactone, furosemide and enalapril or candesartan, it is necessary to monitor serum potassium concentration, even if spironolactone is administered at a low dose of 25 mg/day.

Topics: Adult; Aged; Aged, 80 and over; Benzimidazoles; Biphenyl Compounds; Carbazoles; Carvedilol; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Failure; Humans; Hyperkalemia; Male; Middle Aged; Potassium; Propanolamines; Retrospective Studies; Spironolactone; Tetrazoles

A 67 year old woman developed acute renal failure with serum potassium 9.4 mmol/l requiring emergency dialysis after seven days of diarrhoea while taking an ACE inhibitor for vascular disease. Review of the literature, the British National Formulary, and the patient information leaflets for each of the 11 ACE inhibitors currently marketed in the UK suggests that this potentially life threatening complication of ACE inhibition is not yet widely recognised.

Topics: Acute Kidney Injury; Aged; Angiotensin-Converting Enzyme Inhibitors; Diarrhea; Enalapril; Female; Humans; Hyperkalemia

Topics: Antihypertensive Agents; Diuretics; Electrocardiography; Enalapril; Humans; Hyperkalemia; Male; Middle Aged; Spironolactone

We describe the case of a 77-year old mildly hypertensive woman with no underlying renal disease who was admitted to the Emergency Department (ED) in a comatose state with fever. The patient had been on low dose enalapril and a potassium rich diet. Five days before admission, rofecoxib, a new selective COX-2 inhibitor nonsteroidal anti-inflammatory drug (NSAID), was added for leg pain. She was found to have severe hyperkalemia and died 90 min after her arrival. We cannot absolutely determine whether the COX-2 inhibitor was the dominant contributor to the development of hyperkalemia or the combination itself, with an intercurrent infection and some degree of dehydration. Physicians should be aware of this possible complication and only prescribe NSAIDs, including the new COX-2 drugs, to the elderly under close monitoring of kidney function and electrolyte tests.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cyclooxygenase Inhibitors; Diet; Drug Interactions; Drug Therapy, Combination; Enalapril; Fatal Outcome; Female; Humans; Hyperkalemia; Hypertension; Lactones; Musa; Pain; Sulfones

Topics: Adolescent; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Child; Child, Preschool; Drug Therapy, Combination; Enalapril; Humans; Hyperkalemia; Losartan; Proteinuria; Receptor, Angiotensin, Type 1

Secondary hyperkalaemic paralysis is a rare condition often mimicking the Guillain-Barré syndrome. There have been a few case reports of hyperkalaemia caused by renal failure, trauma, and drugs where the presentation has been with muscle weakness. A case of hyperkalaemic paralysis caused by an angiotensin converting enzyme inhibitor is reported.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Creatinine; Diagnosis, Differential; Electrocardiography; Electrolytes; Enalapril; Guillain-Barre Syndrome; Humans; Hyperkalemia; Male; Paralysis; Water-Electrolyte Imbalance

Topics: Acute Kidney Injury; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Diabetes Mellitus, Type 1; Diuretics; Electrocardiography; Enalapril; Female; Humans; Hyperkalemia; Ibuprofen; Middle Aged; Spironolactone

Acute renal failure and hyperkalemia due to angiotensin-converting enzyme inhibitors have been described in diabetic patients with other predisposing conditions. The case reported here involves a patient with type 1 diabetes mellitus, microalbuminuria and normal renal function who was treated with enalapril. Two years after initiation of this therapy, at a time when glycemic control was poor, he presented with symptomatic hyperkalemia and impaired renal function accompanied by hyporeninemic hypoaldosteronism. This case illustrates that reversible impairment of renal function and hyperkalemia can present after 2 years of treatment with angiotensin-converting enzyme inhibitors in patients with precipitating factors.

Topics: Acute Kidney Injury; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Enalapril; Humans; Hyperkalemia; Hypertension; Hypoaldosteronism; Male; Precipitating Factors

To highlight the dangers of a precipitous rise in serum potassium levels in patients at risk for renal insufficiency, already receiving an angiotensin-converting enzyme (ACE) inhibitor, who are given a potassium-sparing diuretic.. We conducted a retrospective chart review of five patients who were taking the above combination of medications who were seen in our ED with hyperkalemia.. All five patients had diabetes and were older than 50 years of age. Except for one patient, they had some degree of renal impairment and all were receiving an ACE inhibitor. Each had amiloride HCl/hydrochlorothiazide added to their therapeutic regimen 8 to 18 days before presenting to our ED with hyperkalemia. Potassium levels were between 9.4 and 11 mEq/L in 4 of the patients; 2 did not respond to resuscitation measures.. The concomitant use of ACE inhibitor and potassium-sparing diuretic therapy should be avoided. If impossible, weekly monitoring of both renal function and serum potassium should be performed. In the ED patients who are receiving such a combination should receive immediate ECG monitoring.

Topics: Aged; Aged, 80 and over; Amiloride; Angiotensin-Converting Enzyme Inhibitors; Diuretics; Drug Interactions; Drug Therapy, Combination; Enalapril; Female; Humans; Hydrochlorothiazide; Hyperkalemia; Male; Middle Aged; Retrospective Studies; Sodium Chloride Symporter Inhibitors

A 40-year-old woman with transplanted lungs developed life threatening hyperkalaemia (6.8 mmol L-1) during high dose treatment with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia. Trimethoprim has an amiloride-like effect on the distal nephron and may thus induce hyperkalaemia, particularly if other contributing factors coexist. The present patient was also treated with the angiotensin-converting enzyme (ACE) inhibitor enalapril, and the combination of ACE-inhibition and potassium-sparing diuretics is known to induce hyperkalaemia. Hyperkalaemia was probably induced by the combination of ACE-inhibitor and trimethoprim, and this combination may be as dangerous as the combination of ACE-inhibitors with other potassium-sparing diuretics.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Anti-Infective Agents; Enalapril; Fatal Outcome; Female; Humans; Hyperkalemia; Lung Transplantation; Trimethoprim, Sulfamethoxazole Drug Combination

A 66-year-old hypertensive diabetic patient with latent hypoaldosteronism and mild renal failure was treated by adding enalapril, an angiotensin converting enzyme inhibitor, to the furosemide and nifedipine regimen because of an insufficient antihypertensive response for 1 month. Seven days after enalapril addition, the blood pressure was significantly reduced, but frank hyperkalemia occurred with a marked rise in BUN and a slight increase in serum creatinine. Plasma renin activity (PRA) and plasma aldosterone (PA) values remained low before and during enalapril therapy. Transient treatment with sodium polystyrene sulfate after enalapril withdrawal improved the hyperkalemia and renal function, but PRA and PA levels were low. PA and its precursor steroids also responded poorly to graded angiotensin II infusion and rapid ACTH injection. Latent hypoaldosteronism probably predisposed this patient to frank hyperkalemia with progressive dehydration and slightly reduced renal function during antihypertensive therapy.

Topics: Aged; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Therapy, Combination; Enalapril; Furosemide; Humans; Hyperaldosteronism; Hyperkalemia; Hypertension; Kidney Failure, Chronic; Male; Nifedipine

Angiotensin-converting-enzyme inhibitors are frequently used in conjunction with diuretics in the treatment of congestive cardiac failure. We report two cases in which use of a proprietary combination diuretic containing a loop diuretic and potassium sparing agent with an angiotensin converting enzyme inhibitor was associated with hyperkalaemic cardiac arrest. Successful resuscitation from the arrest permitted elucidation of its mechanism. We believe that this outcome has not previously been reported, and emphasise the importance of electrolyte monitoring in patients receiving angiotensin converting enzyme inhibitors particularly if prescribed in addition to fixed combination proprietary diuretics.

Topics: Aged; Amiloride; Angiotensin-Converting Enzyme Inhibitors; Diuretics; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Arrest; Humans; Hyperkalemia

The antihypertensive and renal effects of the angiotensin-converting enzyme inhibitor lisinopril were studied in a group of patients with moderate-to-severe hypertension and impaired renal function. After 12 weeks of treatment, most patients had good blood pressure response to lisinopril monotherapy. During this period, correlations between antihypertensive effect, drug dose, and serum drug level were observed. These correlations were no longer evident after prolonged treatment. During a 1-year follow-up period, the drug dose was lowered gradually without losing antihypertensive effect. Hyperkalemia occurred in one third of the patients. During the 1-year follow-up, the glomerular filtration rate (GFR) decreased in two thirds of the patients and remained stable in the other third. In this latter group, the pretreatment GFR was higher, and the effective renal plasma flow had increased, whereas in the patients with a decreased GFR no renal vasodilation had occurred during lisinopril therapy. Thus, lisinopril is an effective antihypertensive drug for patients with impaired renal function. The dose should be adjusted to the pretreatment GFR, and a decrease in dosage should be considered with prolonged treatment.

Topics: Blood Pressure; Enalapril; Female; Glomerular Filtration Rate; Humans; Hyperkalemia; Hypertension; Kidney Diseases; Lisinopril; Male; Time Factors

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diet, Reducing; Enalapril; Female; Humans; Hyperkalemia; Lisinopril; Middle Aged

We describe the use of fludrocortisone in a patient with systemic lupus erythematosus, who initially presented with moderate renal insufficiency, high serum potassium, metabolic acidosis, low urine pH, and a high urinary anion gap indicating tubular dysfunction. Renal histology revealed membranous glomerulonephritis and interstitial inflammation. During the course of the disease the patient developed persistent severe hyperkalemia. Dietary potassium restriction and therapy with diuretics combined with cation exchange resins failed to decrease potassium levels sufficiently. Drug therapy including cyclosporin A, enalapril, atenolol, phenytoin, necessary to control active disease and severe hypertension contributed to elevated potassium levels. Effective correction of hyperkalemia was achieved by fludrocortisone treatment. We conclude that fludrocortisone is a potent therapeutic approach for selected patients suffering from life threatening hyperkalemia, in whom potassium elevating drugs cannot be withdrawn.

Topics: Adolescent; Atenolol; Creatinine; Cyclosporins; Enalapril; Fludrocortisone; Humans; Hyperkalemia; Kidney; Lupus Erythematosus, Systemic; Male; Phenytoin; Potassium; Renin-Angiotensin System

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Hyperkalemia; Lisinopril; Male; Middle Aged

Topics: Aged; Enalapril; Humans; Hyperkalemia; Hypertension; Middle Aged; Potassium

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Captopril; Death, Sudden; Enalapril; Heart Arrest; Heart Failure; Humans; Hyperkalemia; Hypokalemia; Male; Middle Aged; Potassium; Resuscitation; Substance Withdrawal Syndrome

Topics: Enalapril; Humans; Hyperkalemia; Hypertension, Renal; Kidney Failure, Chronic

Although converting-enzyme inhibition is of established value in the management of patients with severe chronic congestive heart failure, troublesome adverse reactions occur frequently during the course of treatment and may cause physicians to interrupt effective therapy. The three most common adverse reactions that are seen in patients with heart failure following treatment with captopril and enalapril (symptomatic hypotension, functional renal insufficiency, hyperkalaemia) are predictable consequences of interfering with the homeostatic functions of the renin-angiotensin system, which evolved millions of years ago to preserve life in sodium-depleted states. It is not surprising, therefore, that these untoward effects can be prevented or reversed by increasing the dietary intake of salt or reducing the dose of concomitantly administered diuretics; their occurrence rarely requires discontinuation of drug therapy. Recognition of this link between sodium balance and the adverse effects of converting-enzyme inhibition is important, because most patients with severe heart failure who experience such untoward reactions can nevertheless be expected to improve clinically during long-term therapy, if effective treatment is not interrupted.

Topics: Acute Kidney Injury; Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Heart Failure; Humans; Hyperkalemia; Hypotension; Sodium Chloride

Angiotensin I converting enzyme inhibition by captopril and enalapril may influence sodium and potassium homeostasis. In patients without cardiac failure and with normal renal function significant electrolyte disturbances rarely occur. We report on four patients who developed life-threatening electrolyte disturbances following treatment with enalapril for severe cardiac failure (NYHA-class II-IV). There were important concomitant factors in all four cases: in one case under additional medication with a thiazide diuretic and a nonsteroidal antiinflammatory, hyponatremia of 107 mmol/l occurred. In two further cases severe hyperkalemia of 7.4 and 7.3 mmol/l was observed in the presence of acute renal failure due to enalapril-induced hypotension and concomitant therapy with a nonsteroidal antiinflammatory drug respectively. In a fourth case the combination of enalapril with a potassium-sparing diuretic provoked severe hyperkalemia of 7.9 mmol/l.

Topics: Acute Disease; Adult; Aged; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Hyperkalemia; Hyponatremia; Male; Middle Aged; Water-Electrolyte Imbalance

Topics: Aged; Antihypertensive Agents; Dipeptides; Edema; Enalapril; Eosinophilia; Humans; Hyperkalemia; Male; Pruritus