A 3-month double-blind cross-over study of the effect of benazepril and hydrochlorothiazide on functional class in symptomatic mild heart failure. Double-blind comparison of captopril alone against frusemide plus amiloride in mild heart failure. The effects of discontinuing long-term diuretic therapy in the elderly. Symptomatic assessment of patients with heart failure: double-blind comparison of increasing doses of diuretics and captopril in moderate heart failure. Addition of captopril versus increasing diuretics in moderate but deteriorating heart failure: a double-blind comparative trial. Piretanide, a potent diuretic with potassium-sparing properties, for the treatment of congestive heart failure. Amiloride improves hemodynamics in patients with chronic congestive heart failure treated with chronic digoxin and diuretics. Withdrawal of long-term diuretic medication in elderly patients: a double blind randomised trial. Effects of adding spironolactone to an angiotensin-converting enzyme inhibitor in chronic congestive heart failure secondary to coronary artery disease. [Basic therapy of chronic heart failure with digitalis or diuretics?].
The non-sulfhydryl selective angiotensin-converting enzyme inhibitor benazepril (20 mg daily) was compared with hydrochlorothiazide (50 mg daily) in post-infarction (6-24 months) patients with symptomatic (NYHA functional class 2) mild heart failure. No concomitant drug therapy was given. The study had a double-blind cross-over design with 3-month treatment periods. Both drugs were well tolerated, and both caused a similar reduction in systolic blood pressure. Heart rate was higher with the diuretic. Benazepril improved the NYHA functional class in 17 out of 29 (59%) patients, whereas one patient improved with hydrochlorothiazide (P = 0.0004). With regard to global efficacy score, benazepril was also superior. Thus, angiotensin-converting enzyme inhibitors may be superior to diuretics as first-choice therapy in symptomatic mild heart failure. Captopril alone as therapy for mild heart failure was compared with a combination of frusemide and amiloride in a double-blind randomised crossover trial in 14 patients who had previously been treated with diuretics. Although 10 patients remained stable on captopril alone, 4 patients deteriorated, with the development of pulmonary oedema of breathlessness. All 4 patients had had pulmonary oedema previously, unlike the patients who remained stable. Angiotensin converting enzyme inhibition alone is not sufficient treatment for patients with mild heart failure and a history of overt pulmonary oedema. The effects of discontinuing long-term diuretic therapy were investigated by means of a double-blind randomized controlled trial. A total of 141 elderly patients in the long-stay wards of six hospitals were found to be taking maintenance diuretics, and for 33 of these the drugs were judged to be mandatory. Of the remaining patients, 52 continued to receive diuretics while 54 were given matching placebo tablets. Eight in the latter group required diuretic therapy to be resumed during the following 12 weeks. The main change observed in patients who completed the trial was a slight increase of ankle oedema in the placebo group. Plasma potassium levels below 3.5 mEq/1 were found in some patients taking diuretics but not when the drugs had been withdrawn for 12 weeks. Blood pressure rose slightly in the placebo group and plasma urea rose slightly in the diuretic group. It was concluded that old people receiving long-term diuretic therapy without obvious current indication should have the drugs withdrawn under careful supervision so that those needing them could be identified. Ten patients with moderate heart failure who still had symptoms despite 40 mg frusemide daily were treated with increased doses of frusemide and the addition of captopril in randomised order. Four different methods were used to assess the patients' response to treatment. Both treatments improved symptom-limited exercise tolerance, higher-dose frusemide having a more favourable effect. Perceived exertion during submaximal exercise was reduced by similar amounts by both treatments. The time taken to walk 100 m at a self-selected slow speed was reduced by both treatments; again higher-dose frusemide had a more beneficial effect. The higher dose of frusemide also had a more favourable effect on visual analogue scores for dyspnoea, fatigue, and general well-being. In 15 patients with moderate congestive heart failure not completely controlled on digoxin (0.25 mg o.d.) and frusemide (25 mg o.d.), we compared the addition of captopril (12.5 to 50 mg b.i.d.) with increasing doses of frusemide (25 to 100 mg o.d.), in a randomized double-blind, double-dummy, comparative trial. Thirteen patients completed the 3 months study: two dropped-out in the frusemide group. Statistically significant clinical improvement occurred in both treatment groups. Exercise tolerance also significantly improved in both groups in a parallel fashion. Echocardiographic cardiac function data showed a significantly better pattern of changes in the captopril group. The addition of low doses of captopril to basal therapy seems to be as effective as the addition of high doses of frusemide in uncontrolled moderate congestive heart failure. This approach with captopril also appears to be more physiological and safe. The diuretic and clinical efficacy and safety of piretanide, a new high-ceiling loop diuretic, was determined in patients with mild to moderately severe congestive heart failure. Piretanide (n = 20) administered orally in a daily dosage of up to 24 mg was compared with placebo (n = 18) for 28 days, using a double-blind, randomized, parallel design. Patients were hospitalized during the first 5 days of the study when dosage titration was established and 24-hour fractionated urine collections were obtained. Piretanide caused significant diuresis for 3 hours after ingestion with a natriuretic response noted for up to 6 hours. While occasional kaliuretic response was noted, it did not significantly increase 24-hour urinary potassium excretion. Only one patient treated with the highest allowed dose of piretanide developed mild hypokalemia. An improvement in New York Heart Association functional class status was noted after piretanide therapy. In contrast, patients who received placebo exhibited no significant improvement. BUN increased in nine piretanide-treated patients; two were discontinued from the study because of progressive azotemia. However, there was no significant increase in serum creatinine levels. Other blood, physical, ECG, and audiometric examinations also revealed no significant abnormalities. The study suggests that oral piretanide is a relatively safe and effective diuretic for treating congestive heart failure with a potential advantage of having potassium-sparing properties. Potassium-sparing diuretics have been reported to decrease the positive inotropic effect of digoxin. We studied the hemodynamic effects of amiloride in patients taking digoxin for chronic heart failure. Eleven men with a history of congestive heart failure were studied in a double blind, cross-over, placebo controlled trial with the patients on digoxin alternating placebo with amiloride. After 7 days on the trial drug, a Swan-Ganz catheter was placed in the pulmonary artery and measurements made at rest and with increasing degrees of supine bicycle exercise. Right-sided and pulmonary artery wedge pressures and systemic arterial pressures, as well as cardiac outputs, were measured. After a 7 day washout period, placebo (P) and Amiloride (A) were switched and after 7 days on the therapy, a second hemodynamic study at rest and varying degrees of supine bicycle exercise was repeated. At rest there were no significant differences in the right-sided, pulmonary arterial wedge pressure or cardiac outputs between the patients on Amiloride (A) versus placebo (P). During exercise there were significant differences between (P) and (A) at the 50 watt-second stage of exercise.(ABSTRACT TRUNCATED AT 250 WORDS) About 20% of elderly people use long-term diuretic medication, but there is doubt whether prolonged diuretic medication on such a large scale is necessary. We performed a study to assess what proportion may successfully be withdrawn from diuretic therapy.
                Double blind randomised controlled trial with six month follow up.
                General practice.
                202 patients taking long-term diuretics without manifest heart failure or hypertension.
                Patients were allocated to either placebo (withdrawal group, n = 102) or continuation of diuretic treatment (control group, n = 100).
                Occurrence of clinical conditions requiring diuretic therapy based on fixed criteria.
                During follow up diuretic therapy was required in 50 patients in the withdrawal group and 13 in the control group (risk difference 36%; 95% confidence interval 22% to 50%). Heart failure was the most frequent cause of prescribing diuretic therapy (n = 25). Cessation of diuretic therapy caused a mean increase in systolic blood pressure of 13.5 (9.2 to 17.8) mm Hg and in diastolic pressure of 4.6 (1.9 to 7.3) mm Hg.
                Withdrawal of long-term diuretic treatment in elderly patients leads to symptoms of heart failure or increase in blood pressure to hypertensive values in most cases. Any attempt to withdraw diuretic therapy requires careful monitoring conditions, notably during the initial four weeks. In chronic heart failure, a diuretic plus an angiotensin-converting enzyme (ACE) inhibitor only partially suppresses aldosterone despite the fact that aldosterone has many harmful effects independent of angiotensin II. These possible harmful effects of aldosterone are magnesium loss, increased cardiac sympathetic activity, and increased ventricular arrhythmias. We have therefore assessed whether adding the aldosterone antagonist, spironolactone, to a loop diuretic and ACE inhibitor reverses any of these potentially harmful effects of residual aldosterone. In a preliminary animal study, we found that exogenous aldosterone reduced myocardial norepinephrine uptake by 24% in anesthetized rats in vivo. In our main study, 42 patients with New York Heart Association II to III congestive heart failure were randomized to spironolactone (50 to 100 mg/day, titrated to blood pressure and plasma potassium) or placebo in a double-blind fashion. Our principal finding is that cardiac norepinephrine uptake as assessed by 123I-metaiodobenzylguanidine scintigraphy increased with spironolactone (p < 0.01). Spironolactone also elevated plasma magnesium (p < 0.05), reduced urinary magnesium excretion (p < 0.05), and caused a reduction in ventricular arrhythmias on 24-hour ambulatory electrocardiography (p < 0.05). Spironolactone increased plasma renin activity, plasma aldosterone (p < 0.01), 24-hour urinary sodium excretion (p < 0.05), and urinary sodium/potassium ratio (p < 0.01). Echocardiographic-determined measurements of left ventricular systolic and diastolic function were unaltered by spironolactone.(ABSTRACT TRUNCATED AT 250 WORDS) Sixteen patients in heart failure and sinus rhythm were, after a four-week treatment-free period, randomly assigned to receive, for four to six weeks, either a diuretic combination (hydrochlorothiazide + triamterene) or a digitalis glycoside. Subsequently the treatment was exchanged between the two groups. Without treatment nine patients were in stage II (New York Heart Association classification), seven in stage III. Pulmonary wedge pressure at rest was 27 +/- 14, on exercise 32 +/- 8 mm Hg, cardiac output 5.3 +/- 1.0 at rest and 7.8 +/- 2.3 l/min on exercise. Digitalis glycosides improved symptoms by one stage in three of 16 patients. All objective measures showed slight but not significant improvement. Diuretic treatment improved symptoms in five patients, while heart size and echocardiographically measured ventricular volume decreased slightly. Cardiac output decreased at rest, but not significantly, and on exercise not at all. Pulmonary arterial pressure (21 +/- 9 mm Hg), pulmonary wedge pressure (13 +/- 7 mm Hg) and pulmonary artery pressure on exercise (39 +/- 11 mm Hg) were significantly lower on diuretics than without treatment. The results support the primary use of diuretics in the treatment of chronic heart failure.