Showing papers on "Spironolactone published in 1999"

The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.

Abstract: Background and Methods Aldosterone is important in the pathophysiology of heart failure. In a double-blind study, we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting–enzyme inhibitor, a loop diuretic, and in most cases digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily, and 841 to receive placebo. The primary end point was death from all causes. Results The trial was discontinued early, after a mean follow-up period of 24 months, because an interim analysis determined that spironolactone was efficacious. There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent; relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001). This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from prog...

Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II receptor blockade and role in cardiac fibrosis.

Abstract: Background —This study analyzed the regulation and the role of the cardiac steroidogenic system in myocardial infarction (MI). Methods and Results —Seven days after MI, rats were randomized to untreated infarcted group or spironolactone- (20 and 80 mg · kg−1 · d−1), losartan- (8 mg · kg−1 · d−1), spironolactone plus losartan–, and L-NAME– (5 mg · kg−1 · d−1) treated infarcted groups for 25 days. Sham-operated rats served as controls. In the noninfarcted myocardium of the left ventricle (LV), MI raised aldosterone synthase mRNA (the terminal enzyme of aldosterone synthesis) by 2.0-fold and the aldosterone level by 3.7-fold. Conversely, MI decreased 11β-hydroxylase mRNA (the terminal enzyme of corticosterone synthesis) by 2.4-fold and the corticosterone level by 1.9-fold. MI also induced a 1.9-fold increase in cardiac angiotensin II level. Such cardiac regulations were completely prevented by treatment of the infarcted heart with losartan. The MI-induced collagen deposition in noninfarcted LV myocardium was prevented by 1.6-fold by both low and high doses of spironolactone and by 2.5-fold by losartan. In addition, norepinephrine level was unchanged in infarcted heart but was attenuated by both losartan and spironolactone treatments. Conclusions —MI is associated with tissue-specific activation of myocardial aldosterone synthesis. This increase is mediated primarily by cardiac angiotensin II via AT1-subtype receptor and may be involved in post-MI ventricular fibrosis and in control of tissue norepinephrine concentration.

Role of Aldosterone in Renal Vascular Injury in Stroke-Prone Hypertensive Rats

Abstract: —Stroke-prone spontaneously hypertensive rats (SHRSP) on 1% NaCl drinking solution and Stroke-Prone Rodent Diet develop severe hypertension and glomerular and vascular lesions characteristic of thrombotic microangiopathy seen in malignant nephrosclerosis. We recently reported that spironolactone, a mineralocorticoid receptor antagonist, markedly reduced proteinuria and malignant nephrosclerotic lesions in these animals. This observation, together with our previous findings that angiotensin-converting enzyme inhibitors prevent the development of vascular damage, suggests that mineralocorticoids, as part of the renin-angiotensin-aldosterone system, play a pathophysiological role in this model. In the present study, we examined whether chronic (2-week) infusion of aldosterone can reverse the renal vascular protective effects of captopril in SHRSP. SHRSP received vehicle (n=8); captopril alone (50 mg · kg −1 · d −1 , orally) (n=10); aldosterone infusion alone (40 μg · kg −1 · d −1 , SC) (n=7); or captopril and aldosterone at 20 (n=6) or 40 (n=7) μg · kg −1 · d −1 . Systolic blood pressure was markedly elevated in all groups. Vehicle- and aldosterone-infused SHRSP developed severe proteinuria and comparable degrees of renal injury (21±3% and 29±3%, respectively) manifested as thrombotic and proliferative lesions in the arterioles and glomeruli. Captopril treatment reduced plasma aldosterone levels concomitant with marked reductions in proteinuria and the absence of histologic lesions of malignant nephrosclerosis. Aldosterone substitution at 20 or 40 μg · kg −1 · d −1 in captopril-treated SHRSP resulted in the development of severe renal lesions (16±3% and 21±2%, respectively) and proteinuria comparable with that observed in SHRSP given either aldosterone or vehicle alone. These findings support a major role for aldosterone in the development of malignant nephrosclerosis in saline-drinking SHRSP, independent of the effects of blood pressure.

Aldosterone Upregulates Ca2+ Current in Adult Rat Cardiomyocytes

Abstract: Aldosterone is associated with the pathogenesis and progression of left ventricular hypertrophy and heart failure, independent of its relation with arterial blood pressure. However, little information exists about the possible influence of this mineralocorticoisteroid on cardiomyocyte electrical activity. The present study was designed to determine the role of aldosterone on whole-cell Ca 21 current (ICa) in isolated adult rat ventricular myocytes using the patch-clamp technique. We found that incubation of cells with 1 mmol/L aldosterone for 24 hours increases the density of ICa significantly. This "long-term" aldosterone treatment had no significant effects on the kinetics and voltage dependence of ICa inactivation. Moreover, no demonstrable influence of aldosterone on ICa could be detected during short-term exposure (up to 6 hours), under our experimental conditions. The classical aldosterone intracellular receptor antagonist spironolactone (250-fold excess) was able to blunt the aldosterone-induced increase in ICa density. These effects were also observed with lower concentrations of aldosterone (10 and 100 nmol/L). Moreover, inhibitors of transcription (actinomycin D, 5 mg/mL) and protein synthesis (cycloheximide, 20 mg/mL) prevented the aldosterone-dependent increase in ICa. Therefore, the long latency ICa stimulation effect of aldosterone might result from an increased channel expression. We suggest that this genomic action contributes to the increased ICa observed during cardiac remodeling. (Circ Res. 1999;85:1139-1145).

Raised aldosterone to renin ratio predicts antihypertensive efficacy of spironolactone: a prospective cohort follow-up study.

Abstract: Aims Aldosterone/renin ratio is an index for inappropriate aldosterone activity, and it is increasingly being used to screen for primary aldosteronism within the hypertensive population. It may also be a good index to help predict the response to spironolactone. To assess the blood pressure response to oral spironolactone in hypertensive patients with primary aldosteronism identified with raised aldosterone to renin ratio. Methods We conducted a prospective cohort study of hypertensive patients with raised aldosterone/renin ratio, who failed to suppress plasma aldosterone with salt loading and fludrocortisone suppression test. These patients were treated with spironolactone and were followed-up for a period of up to 3 years. Results We studied 28 (12 male) subjects with a mean age of 55 (s.d. 10) years who were followed up for a mean period of 12.9 (7) months. At baseline, the patients were taking a mean of 2.1 (1.2) antihypertensive drugs, but despite this 16/28 (57%) had diastolic BP >90 mmHg, 39% with systolic BP >160 mmHg. After commencing spironolactone, three patients complained of breast tenderness but continued treatment and one patient was intolerant of spironolactone and had to stop treatment. Of the remaining 27 patients, the mean number of antihypertensive drugs used dropped to spironolactone plus 0.7 (s.d. 0.9). All but one patient (96%) achieved a diastolic BP≤90 mmHg and 78% achieved a systolic BP≤160 mmHg. In total 48% had BP≤140/90 mmHg and 13/27 (48%) were treated with spironolactone monotherapy. Assessing only patients on drug treatment at baseline (n=24), spironolactone significantly reduced the need for antihypertensive drugs by −0.5 (CI 0.1–1.0), P=0.02, as well as reducing blood pressure [systolic BP −15 mmHg (CI 5–25), P=0.007 and diastolic BP (mmHg) by −8 mmHg (CI 4–13), P=0.001]. Conclusions Spironolactone was a highly effective antihypertensive agent in hypertensive patients who had a raised aldosterone/renin ratio. As a raised ratio was highly predictive of nonsuppression of plasma aldosterone suggesting primary aldosteronism, it might be worthwhile using spironolactone in this subgroup of hypertensive patients with raised aldosterone/renin ratios, provided that adrenal adenomas are excluded with imaging techniques.

Aldosterone and Spironolactone in Heart Failure

Abstract: Chronic heart failure occurs most commonly after earlier myocardial infarction or in the presence of long-standing hypertension. The inability of this normally efficient muscular pump to eject or r...

Effects of spironolactone and angiotensin-converting enzyme inhibitor on left ventricular hypertrophy in patients with essential hypertension.

Abstract: There is increasing evidence for important cardiovascular effects of aldosterone via classical mineralocorticoid receptors in the heart. Administration of aldosterone with excess salt produces both cardiac hypertrophy and interstitial cardiac fibrosis in rats, and concomitant administration of potassium canrenoate at a dose that only modestly lowers blood pressure completely blocks the cardiac effects of aldosterone. In the present study, we examined the effect on left ventricular hypertrophy of adding a low dose of the mineralocorticoid receptor antagonist spironolactone (25 mg/d) to an angiotensin-converting enzyme inhibitor (enalapril maleate) in patients with essential hypertension. Eighteen untreated patients with moderate to severe essential hypertension based on the WHO/ISH guidelines participated in this study. Subjects were treated with either an angiotensin-converting enzyme inhibitor alone (group I: 10 patients, 4 men and 6 women, mean age 56 +/- 18 yr) or an angiotensin-converting enzyme inhibitor plus spironolactone (group II: 8 patients, 3 men and 5 women, mean age 59 +/- 14 yr) for 9 mo. Left ventricular mass index, various echocardiographic variables, mean blood pressure, plasma renin activity, and plasma aldosterone concentration before treatment were similar in the two groups. Blood pressure of both groups decreased significantly and similarly after antihypertensive treatment (group I, 136 +/- 9/82 +/- 9 mmHg; group II, 133 +/- 9/85 +/- 10 mmHg). Left ventricular mass index also decreased significantly in both groups (group I, -10.2 +/- 7.1%; group II, -18.1 +/- 6.9%). The extent of reduction was significantly greater in the spironolactone group (group II) (p < 0.05 vs. group I). In group II patients, spironolactone did not cause any side effects during the observation period. We conclude that spironolactone may have beneficial effects on left ventricular hypertrophy in patients with essential hypertension who are receiving an angiotensin-converting enzyme inhibitor.

Why does spironolactone improve mortality over and above an ACE inhibitor in chronic heart failure

Abstract: The Randomised Aldosterone Evaluation Study (RALES) was recently terminated prematurely because it demonstrated that spironolactone was superior to placebo at reducing death in patients with moderate to severe chronic heart failure who were already being treated with standard therapy including an ACE inhibitor. This is a very important finding as it should directly influence the clinical management of patients with moderate to severe CHF. Its other major impact is that it should be possible to use the RALES results to provide important mechanistic clues as to why the CHF disease process progresses towards death. This article will therefore address the question of what are the possible mechanisms whereby spironolactone improves mortality in CHF?

Spironolactone, but not flutamide, administration prevents bone loss in hyperandrogenic women treated with gonadotropin-releasing hormone agonist.

Abstract: GnRH agonists (GnRHa) have recently been proposed for the treatment of hirsutism in women with the polycystic ovary syndrome (PCOS). As most of these subjects have increased androgen secretion from both ovaries and adrenal glands, the association of GnRHa with antiandrogen drugs might enhance the clinical response to treatment. On the other hand, this association might also potentiate the adverse effects of GnRHa on bone metabolism, generating a potentially harmful situation at the skeletal level. In this study we investigated in 41 PCOS patients the skeletal effects of a 6-month course of GnRHa (tryptorelin, 3.75 mg, im, monthly), either alone (n = 12) or associated with the antiandrogen drugs spironolactone (100 mg, orally, once daily; n = 14) or flutamide (250 mg, once daily; n = 15). In all subjects bone mineral density was measured before and after treatment by dual energy x-ray absorptiometry at the lumbar spine (L2–L4) and at the femoral neck and Ward’s triangle. In addition, at baseline and after ...

Combination therapy of angiotensin converting enzyme inhibitor and aldosterone antagonist for reducing morbidity and mortality from cardiovascular disease

Abstract: Combinations of an ACE inhibitor, an aldosterone antagonist, and a loop diuretic are described for use in treatment of circulatory disorders Of particular interest are therapies using captopril, enalapril or lisinopril co-administered with spironolactone This co-therapy would be particularly useful to reduce the death rate or the number of non-fatal hospitalizations or prevent the progression of congestive heart failure in patients with cardiovascular disease

Bartter's syndrome in Arabic children: review of 13 cases.

Abstract: Background: Bartter's syndrome (BS) is an inherited disease of renal potassium wasting characterized by hypokalemic alkalosis, normal blood pressure, vascular insensitivity to pressor agents and elevated plasma concentrations of renin and aldosterone. It is caused by generalized hyperplasia of the juxtaglomerular apparatus at the site of renin production caused by mutations in the Na–K–2Cl cotransporter gene, NKCC2. The objective of our study is to establish the prevalence and incidence of BS in Kuwait and to assess treatment modalities for it. Methods and Results: Bartter's syndrome was diagnosed in 13 Kuwaiti children over a 14 year period (1981–1995) with the estimated incidence of 1.7/100 000 live births. The mean age at diagnosis was 9.3 months (range 2–32 months). There were five males and eight females (ratio 1:1.6). The mean duration of follow up was 5.6 years (1–14 years). Both consanguinity and familial history among our patients were high (69 and 54%, respectively). All patients had hypokalemia, hypochloremia with metabolic alkalosis, hyper-reninemia and were normotensive. Clinical presentation was essentially similar to that in other series. Eleven patients (85%) had growth failure, two had nephrocalcinosis (15%) and one had renal failure. All patients were treated with supplemental potassium, an aldosterone antagonist (spironolactone) and a prostaglandin synthetase inhibitor (indomethacin or aspirin) sequentially. Significant catch-up of growth (four patients) and increases in serum potassium (eight patients) were recorded after administration of indomethacin therapy. One patient died of severe pneumonia with respiratory failure from hypokalemic myopathy. Clinical presentation, inheritance, complications and therapy of BS are briefly discussed. Conclusion: Bartter's syndrome is a rare disease, but should be considered in the differential diagnosis of other disorders with growth failure and/or hypokalemia. Early diagnosis, close follow up and compliance with treatment may lead to appropriate growth and development.

Spironolactone, but not flutamide, administration prevents bone loss in hyperandrogenic women treated with gonadotropin-releasing hormone agonist

Abstract: GnRH agonists (GnRHa) have recently been proposed for the treatment of hirsutism in women with the polycystic ovary syndrome (PCOS). As most of these subjects have increased androgen secretion from both ovaries and adrenal glands, the association of GnRHa with antiandrogen drugs might enhance the clinical response to treatment. On the other hand, this association might also potentiate the adverse effects of GnRHa on bone metabolism, generating a potentially harmful situation at the skeletal level. In this study we investigated in 41 PCOS patients the skeletal effects of a 6-month course of GnRHa (tryptorelin, 3.75 mg, im, monthly), either alone (n 5 12) or associated with the antiandrogen drugs spironolactone (100 mg, orally, once daily; n 5 14) or flutamide (250 mg, once daily; n 5 15). In all subjects bone mineral density was measured before and after treatment by dual energy x-ray absorptiometry at the lumbar spine (L2‐L4) and at the femoral neck and Ward’s triangle. In addition, at baseline and after 6 months of therapy, bone metabolism markers (serum and urinary calcium, serum phosphorus and alkaline phosphatase, plasma osteocalcin, and urinary hydroxyproline) and endocrine parameters (serum gonadotropins, estradiol, and free testosterone) were assayed. Women given either GnRHa alone or associated with spironolactone or flutamide were similar for age and body mass index. At baseline, the 3 groups of PCOS women were also similar for endocrine and bone parameters. After 6 months, all treatments determined similar striking suppressions of serum gonadotropins and sex steroids. Concurrently, bone mineral density was significantly reduced at all examined sites in subjects receiving either GnRHa alone or GnRHa plus flutamide. Conversely, women given GnRHa plus spironolactone did not show any change in skeletal mass from baseline values (P , 0.05‐ 0.01 among groups). Biochemical parameters of bone metabolism were consistent with densitometric assessments. In conclusion, after a 6-month course of therapy, bone mineral density is reduced in PCOS women given either GnRHa alone or GnRHa plus flutamide, but not in those receiving GnRHa plus spironolactone. The mechanisms of the bone-sparing effect of spironolactone remain to be determined. Nevertheless, this drug could represent a useful tool to prevent skeletal loss in women given GnRHa as well as in other hypoestrogenic conditions, in particular when estrogens are not recommended. (J Clin Endocrinol Metab 84: 1250 ‐1254, 1999)

Persistent hypokalemia after successful adrenalectomy in a patient with Cushing’s syndrome due to ectopic ACTH secretion: Possible role of 11β-hydroxysteroid dehydrogenase inhibition

Abstract: Ectopic ACTH secretion is characterized by a high incidence of hypokalemia. The pathophysiology of hypokalemia has not been totally clarified, although it has been postulated that excessive amounts of adrenal steroids may play a role, as well as a possible role of the inhibition of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD). This enzyme normally converts cortisol to cortisone avoiding the mineralocorticoid action of cortisol. We present a patient with ectopic ACTH secretion due to a metastatic carcinoid tumor. The clinical picture was characterized by maintained hypokalemia (1.4 mmol/l) resistant to potassium, spironolactone and ketoconazole administration. A bilateral adrenalectomy was performed but the hypokalemia persisted while he was receiving a physiological dose of cortisol. Eight days after adrenalectomy cortisol was replaced by an equivalent dose of dexamethasone. This change was followed by a rapid and persistent normalization of hypokalemia suggesting a mineralocorticoid effect of cortisol. In conclusion, the origin of hypokalemia in our patient with ectopic ACTH secretion was secondary to cortisol. We postulate that this peculiar effect of cortisol could have happened if an inhibition of 11beta-OHSD occurred.

Influence of spironolactone on neonatal screening for congenital adrenal hyperplasia.

Abstract: AIM To determine if the diuretic spironolactone cross reacts with 17α-hydroxyprogesterone (17OHP) in an enzyme linked immunosorbent assay (ELISA) kit used for the mass screening of congenital adrenal hyperplasia. METHODS Concentrations of 17OHP on a blood filter paper disc were measured using an ELISA kit (kit C-7: ENZAPLATE N-17α -OHP-7; Chiron, Tokyo, Japan). The cross reactivity of spironolactone and its metabolites with 17OHP was determined. The concentrations of spironolactone and its metabolites in blood were measured using HPLC (high performance liquid chromatography). RESULTS Spironolactone cross reacted with 17OHP using kit C-7 (0.01%), by increasing 17OHP concentration in a dose dependent manner. The blood concentration of spironolactone and its metabolites was nearly 900 ng/ml, high enough to show an additive effect on the 17OHP concentration. About 12% of the false positive cases screened using the kit were due to the administration of spironolactone. CONCLUSIONS Spironolactone interferes with 17OHP concentrations, leading to false positive test results for CAH.

Study of the month. The RALES study (randomized aldactone evaluation study

Abstract: RALES was a double-blind study which enrolled 1.663 patients with severe heart failure and a left ventricular ejection fraction of no more than 35 percent who were being treated with an angiotensin-converting-enzyme inhibitor, a loop diuretic and, in most cases, digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily and 841 to receive placebo. The primary end point of the study was death from all causes. The trial was discontinued early after a mean follow-up of 24 months because an interim analysis determined that spironolactone was efficacious. There were indeed 386 deaths in the placebo group (46%) and 284 in the spironolactone group (35%) (relative risk of death: 0.70; 95% confidence interval, 0.60-0.82; p < 0.001). The reduction of mortality among patients in the spironolactone group was attributable to a lower risk of sudden cardiac death and of death from progressive heart failure. Patients treated by spironolactone had a lower hospitalization rate for worsening heart failure; they also had a significant improvement in the symptoms of heart failure as assessed by the New York Heart Association functional class. Serious hyperkalemia was minimal in both groups of patients. Gynecomastia or breast pain was reported in 10% of men who were treated with spironolactone as compared with 1% of men in the placebo group (p < 0.001).

[Role of cardiac aldosterone in post-infarction ventricular remodeling in rats].

Abstract: Synthesis of aldosterone (Aldo) and corticosterone (B) has been recently reported in rat heart. However, regulation of this synthesis in pathophysiological states remains unknown. Thus, this study aimed to analyze effects of a one-month myocardial infarction (MI) on cardiac steroidogenic system. Levels of terminal enzymes of B (11 beta-hydroxylase: 11 beta H) and aldo (Aldo-synthase: AS) synthesis were assayed by quantitative RT-PCR. Cardiac Aldo and B levels were assessed by celite colum chromatography and radioimmunoassay. MI raised AS mRNA levels by 2.0-fold (p < 0.05) but downregulated that of 11 beta H by 2.4 fold (p < 0.05) in the noninfarcted part of the left ventricle (LV). Cardiac steroids production followed a similar pattern of regulation. Aldo level was increased in MI (319 +/- 85 vs 87 +/- 11 pg/mg of protein in control, p < 0.05) whereas that of B fell (2,412 +/- 318 vs 4,624 +/- 857 pg/mg of protein in control, p < 0.05). MI also induced an 1.9-fold increase in cardiac Ang II level. Such cardiac regulations were prevented by Ang II-AT1 receptor antagonist losartan (8 mg/kg/day) treatment. The Aldo receptor antagonist spironolactone (20 mg/kg/day) had no effect. Plasma Aldo and B, and adrenal 11 beta H and AS mRNA levels were unchanged whatever the treatment. The MI-induced collagen deposition in noninfarcted area of the LV was reduced by both spironolactone and losartan treatments by 1.6- and 2.5-fold, respectively. These data indicate that MI is associated with tissue-specific activation of myocardial aldosterone synthesis. This activation is mediated by cardiac Ang II via AT1 receptor and the resultant increase of intracardiac aldosterone level may be involved in post-MI ventricular remodeling.

Chronic Heart Failure.

Abstract: Physicians must aggressively treat heart failure in the early stages to prevent disease progression and improve survival. Early treatment implies early diagnosis of left ventricular (LV) dysfunction, before the onset of symptoms. Patients with risk factors for the development of heart failure, especially coronary disease or hypertension, should undergo echocardiography to evaluate LV function. Patients with LV systolic dysfunction should be further evaluated to determine the type of cardiac dysfunction, uncover correctable etiologic factors, determine prognosis, and guide treatment. Angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking drugs improve survival and are integral to the treatment plan. Physicians should prescribe an ACE inhibitor as initial therapy for all patients with LV systolic dysfunction unless there are specific contraindications. The combination of hydralazine and isosorbide dinitrate is an acceptable alternative therapy for patients who cannot take ACE inhibitors. Diuretics should be used if there are signs or symptoms of volume overload. Beta-adrenergic blocking drugs should be added to therapy in stable patients with mild to moderate heart failure after optimal treatment with ACE inhibitors, diuretics, or other vasodilators. Digoxin should be used routinely in patients with severe heart failure and should be added to therapy in patients with mild to moderate heart failure who remain symptomatic despite optimal doses of ACE inhibitors and diuretics. Spironolactone should be added, but electrolytes should be closely monitored. Warfarin anticoagulation should be considered in patients with a left ventricular ejection fraction (LVEF) of 35% or less. Until survival data exist, angiotensin receptor blockers (ARBs) should not be used as initial therapy or as sole therapy but can be used for ACE-intolerant patients or can be added to standard heart failure therapy. Outpatient use of intravenous inotropic therapy should be avoided. Patients with severe heart failure should have peak oxygen consumption measured to quantify functional impairment, determine prognosis, and identify the need for advanced heart failure therapy. Patients who remain symptomatic while receiving optimal standard therapy should be referred early to a specialized heart failure center.

[Drug-related hyperkalemia resulted from spironolactone and angiotensin converting enzyme inhibitors therapy].

Abstract: A case of drug-related hyperkaliemia linked to treatment with angiotensin converting enzyme inhibitors and spironolactone simultaneously. The paper presents the case of drug-related hiperkaliemia induced by captopril and spironolactone combined treatment in a patient with early stage of renal failure.

Drug cuts deaths from heart failure by a third.

Abstract: Deaths and admissions to hospital resulting from chronic heart failure can be reduced by nearly a third by giving patients the 30 year old diuretic spironolactone, according to a new study; until now, the drug has not been thought to be useful in treating patients with heart disease. The new study enrolled 1663 men and women in 15 countries, all diagnosed with severe type III or type IV heart failure. About half of the participants received conventional drug treatment, including …

A review of evidence of benefits from ACE inhibitors in heart failure compared with AT1 receptor blockers and other therapies

Abstract: A number of large controlled trials have shown that angiotensin-converting enzyme (ACE) inhibitors reduce mortality and morbidity in patients with chronic heart failure, and can prevent the development of heart failure in asymptomatic patients with left ventricular dysfunction. Research has shown, however, that regardless of the evidence proving the benefits of ACE inhibitors in the management of heart failure, they are still under-used in clinical practice. In their place, newer treatments, such as AT 1 receptor blockers, are being prescribed, despite the lack of conclusive evidence demonstrating their benefits in the management of heart failure. It is therefore recommended that ACE inhibitors should be first-line therapy in all patients with heart failure, unless contraindications are present. The results of the Assessment of Treatment with Lisinopril and Survival (ATLAS) Study suggest that the highest tolerated doses should be used to achieve maximum benefit (up to 35 mg of lisinopril). AT 1 receptor blockers should be reserved for those patients who are unable to tolerate ACE inhibitors. Recent studies suggest that beta-blockers may provide additional benefits in patients with Class II-III heart failure, and that the addition of spironolactone should be considered in patients with severe (Class IV) heart failure.

[Drug-interactions and adverse effects of losartan potassium, an angiotensin II receptor antagonist].

Abstract: Losartan potassium is mainly metabolized by P450 chiefly in the liver. A P450 inducer, phenobarbital, has no significant effects on the pharmacokinetics of losartan. Cimetidine, known to inhibit P450 activity, has no remarkable effects on the metabolism of losartan. Side effects of losartan has been very few in the clinical trials of this drug on several thousands of patients so far. The rate was as low as that of placebo. Losartan may cause hyperkalemia when used with potassium-sparing diuretics, such as spironolactone or triamterene. Angioedema and acute hepatitis had been reported in 3 patients among thousands of millions of hypertensives under losartan treatment. The etiology was unclear, simple coincidence may not be ruled out. Losartan should not be administered to pregnant women and breast-feeding mothers, because it may disturb the fetal growth or may be harmful to the newborn. It should be cautiously used in patients with renal failure or liver disfunction.

A case of nephrotic syndrome with diabetes mellitus and primary aldosteronism

Abstract: A 65-year-old man had been followed by a family doctor for the treatment of hypertension and chronic hepatitis (type C) for about 20 years. Although he was pointed out to have impaired glucose tolerance and primary aldosteronism in 1995, he refused an adrenal tumor operation. He was admitted to our hospital on December, 1997 for further evaluation of general malaise, pitting edema of the legs, and positive urinary protein. A diagnosis of nephrotic syndrome was made on admission and a renal biopsy was performed. Histological findings indicated that he was at the early phase of diabetic nephropathy and hypertensive renal sclerosis. It is commonly believed that diabetic nephropathy develops after ten years of diabetic history and under poor control conditions. The diabetic history of this patient was only several years and the disease was under good control. In contrast to blood glucose, hypertension was not well-controlled with any antihypertensive drug, because he had a primary aldosteronism. Unfortunately, he could not take a spironolactone because of side effects. After removal of his adrenal tumor, his blood pressure was normalized gradually, and concomitantly his urinary protein was reduced and plasma protein and albumin were restored. Hypokalemia also disappeared. These findings suggest that uncontrolled hypertension may have accelerated the condition of diabetic nephropathy. The data indicates that the control of hypertension is important for inhibiting the progression of diabetic nephropathy.