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PubMed2002

Diuretics, mortality, and nonrecovery of renal function in acute renal failure.

CONTEXT: Acute renal failure is associated with high mortality and morbidity. Diuretic agents continue to be used in this setting despite a lack of evidence supporting their benefit. OBJECTIVE: To determine whether the use of diuretics is associated with adverse or favorable outcomes in critically ill patients with acute renal failure. DESIGN: Cohort study conducted from October 1989 to September 1995. PATIENTS AND SETTING: A total of 552 patients with acute renal failure in intensive care units at 4 academic medical centers affiliated with the University of California. Patients were categorized by the use of diuretics on the day of nephrology consultation and, in companion analyses, by diuretic use at any time during the first week following consultation. MAIN OUTCOME MEASURES: All-cause hospital mortality, nonrecovery of renal function, and the combined outcome of death or nonrecovery. RESULTS: Diuretics were used in 326 patients (59%) at the time of nephrology consultation. Patients treated with diuretics on or before the day of consultation were older and more likely to have a history of congestive heart failure, nephrotoxic (rather than ischemic or multifactorial) origin of acute renal failure, acute respiratory failure, and lower serum urea nitrogen concentrations. With adjustment for relevant covariates and propensity scores, diuretic use was associated with a significant increase in the risk of death or nonrecovery of renal function (odds ratio, 1.77; 95% confidence interval, 1.14-2.76). The risk was magnified (odds ratio, 3.12; 95% confidence interval, 1.73-5.62) when patients who died within the first week following consultation were excluded. The increased risk was borne largely by patients who were relatively unresponsive to diuretics. CONCLUSIONS: The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function. Although observational data prohibit causal inference, it is unlikely that diuretics afford any material benefit in this clinical setting. In the absence of compelling contradictory data from a randomized, blinded clinical trial, the widespread use of diuretics in critically ill patients with acute renal failure should be discouraged.

Acute Kidney Injury↗
PubMed1993

Clinicopharmacological reappraisal of the potency of diuretics.

From a clinicopharmacological standpoint, the urinary excretory potency of diuretics should be assessed comparatively on the basis of the changes in 24-hour natriuresis, with respect to 24-hour natriuresis after placebo, caused by single oral doses administered to healthy adult subjects who are in habitual and steady-state external sodium balance. The potency of various formulations of loop (e.g., furosemide), of early distal tubular (e.g., the thiazides), and of potassium-retaining diuretics, as well as of several combinations of diuretics, has been evaluated in a series of studies. Two formulations of loop diuretics (muzolimine 20 mg and torasemide 2.5 mg) are definitely nondiuretic. The majority of the other formulations of loop diuretics studied are, in general, comparatively less potent than most of the common formulations of early distal tubular diuretics studied. As a general rule, most common formulations of early distal tubular diuretics are at least not less potent than the majority of common formulations of loop diuretics. Hydrochlorothiazide 25 mg and furosemide 80 mg have similar potencies. Loop diuretics increase mean renal sodium output strikingly within the first few (0-6) hours after dosing, but this forced excretion is followed by a rebound with respect to postplacebo mean urinary sodium flow; the rebound usually takes place between 6 and 24 hours after dosing. However, no rebound in mean urinary sodium flow occurs during the 24 hours following a single dose of a distal tubular diuretic; these substances increase urinary sodium excretion with lower maximal intensity but more protractedly than loop diuretics.(ABSTRACT TRUNCATED AT 250 WORDS)

Clopamide↗
PubMed2002

Current evidence supporting the role of diuretics in heart failure: a meta analysis of randomised controlled trials.

OBJECTIVE: To summarise the current evidence from randomised controlled trials for diuretics in patients with congestive heart failure (CHF). DATA SOURCES: English-language randomised controlled trials and review papers referenced in Medline, Embase between 1966 and 1999. General literature review of pertinent journals was carried out and reference lists of papers were inspected. REVIEW METHOD STUDY DESIGN: Meta-analysis of randomised controlled trials of diuretic therapy in patients with CHF. STUDY SELECTION: Studies were included if they were randomised comparisons of loop or thiazide diuretics and control, or one diuretic and another active agent (e.g. ACE inhibitors, ibopamine and digoxin). DATA ABSTRACTION: Using a standardised protocol, two reviewers independently abstracted the data and assessed the methodological quality of each paper. DATA SYNTHESIS: The odds ratio (OR) of treated group compared with control was estimated for each end-point outcome and plotted against each other using the fixed-effects model. THE MAIN OUTCOME MEASURES: The primary outcomes of our analysis were effects of diuretics on mortality and morbidity. RESULTS: Eighteen trials met our criteria and were eligible for analysis, involving 928 patients. Eight trials were placebo-controlled. We analysed the data for mortality and for worsening heart failure. A further ten trials compared diuretics against other agents such as ACE inhibitors, ibopamine, and digoxin. Mortality data were available in three of the placebo-controlled trials (n=221); the mortality rate was lower for patients treated with diuretics than for control [the odds ratio for death, 0.25; 95% confidence intervals (CI), 0.07-0.84; P=0.03]. Admissions for worsening heart failure in the four small trials (n=448) showed an odds ratio of 0.31 (95% CI 0.15-0.62; P=0.001). In six studies of diuretics compared to active control, diuretics significantly improved exercise capacity in patients with CHF [OR: 0.37; CI: 0.10-0.64, P=0.007]. CONCLUSION: Compared to active control, diuretics appear to reduce the risk of worsening disease and improve exercise capacity. The available data from small studies show that in CHF conventional diuretics reduce the risk of death and worsening heart failure compared to placebo.

Diuretics↗
PubMed2001

Long-term diuretic therapy in patients with coronary disease: increased colon cancer-related mortality over a 5-year follow-up.

OBJECTIVES: Recent studies have suggested that long-term diuretic therapy may be associated with increased risk of renal cell carcinoma. This carcinoma is not a common malignancy, but it shares risk factors with the considerably more widespread colon cancer (CC). However, there are no data whether or not a relationship between long-term diuretic therapy and CC mortality exists. In this study we tested the hypothesis that long-term diuretic therapy may be associated with increased CC mortality over a 5.6-year follow-up period. SUBJECTS AND METHODS: The study sample comprised 14 166 patients aged 45 to 74 years with a previous myocardial infarction and/or stable anginal syndrome, screened for participation in the bezafibrate infarction prevention (BIP) study. There were 2153 patients receiving diuretics and 12 013 patients receiving no diuretics. RESULTS: During the follow-up 139 (6.5%) new cases of cancer were diagnosed in the diuretic-treated group compared with 622 (5.2%) in the group receiving no diuretics (P = 0.02). Colon cancer mortality was significantly higher in the diuretic-treated patients (0.1 vs 0.5%, P = 0.001), whereas mortality differences for other cancer types were not documented. Multivariate analysis identified diuretics as an independent predictor of increased colon cancer incidence and colon cancer mortality with a hazard ratio (HR) of 2.0 (95% CI 1.2-3.2) for colon cancer incidence and 3.7 (95% CI 1.7-8.3) for mortality. However, the association between diuretic therapy and higher incidence of colon cancer was observed only among non-users of aspirin. A relatively lower colon cancer incidence was observed in the furosemide subgroup, and higher in the small combined amiloride/hydrochlorthiazide subgroup (HR 3.15, 95% CI 1.15-8.65). CONCLUSION: Long-term exposure to diuretic therapy may be associated with an increased colon cancer-related mortality.

Aged↗
PubMed2005

Renal effects of treatment with diuretics, octreotide or both, in non-azotemic cirrhotic patients with ascites.

BACKGROUND: Diuretic-induced hyperreninaemia is associated with renal dysfunction in cirrhotic patients with ascites, and in turn prevents the use of high doses of diuretics. Furthermore, ample evidence suggests that octreotide can inhibit the activation of the renin-aldosterone axis. The present study investigated the renal effects of the addition of octreotide to furosemide and spironolactone in the treatment of non-azotemic cirrhotic patients with ascites. METHODS: We studied 20 patients treated with furosemide and spironolactone. Of them, 10 (Group 1) discontinued diuretic treatment for 7 days. Thereafter, for 5 days each patient received subcutaneous octreotide 300 microg b.i.d., in 10 patients (Group 2) in addition to their usual diuretics. We collected data on the patients while they received diuretics (both groups), after discontinuation of diuretics (Group 1), and after octreotide administration (both groups). RESULTS: We observed a trend to increase creatinine clearance and a significant reduction in plasma active renin and plasma aldosterone after the discontinuation of diuretics. The subsequent introduction of octreotide reduced glomerular filtration rate, although it significantly decreased plasma active renin and plasma aldosterone. In contrast, the addition of octreotide to diuretic treatment significantly increased glomerular filtration rate, urine volume and sodium excretion. The magnitudes of the decreases in plasma-active renin and aldosterone produced by the combination of octreotide and diuretics were similar to those produced by octreotide alone or by the discontinuation of diuretics. CONCLUSIONS: Octreotide alone does not improve renal function in cirrhotic patients with ascites. On the contrary, adding it to diuretic treatment increases glomerular filtration rate and sodium and water excretion, mainly through the suppression of an activated renin-aldosterone axis.

Adult↗
PubMed1984

Diuretics in long-term treatment of hypertension: a comparison to beta-blockers.

Diuretics are first-line drugs for treatment of hypertension in most parts of the world. Recently, however, beta-blockers have been increasingly used as drugs of first choice. The aim of this review is to describe advantages and disadvantages of diuretics in comparison to beta-blockers. The blood pressure (BP)-lowering effect of normally used doses of diuretics gives a useful decrease of BP equal to what can be achieved with beta-blockers in corresponding doses. Over 20 years of use has shown diuretics to be relatively safe for long-term treatment. The frequency of withdrawals and the subjective tolerability are comparable to those with beta-blockers. Diuretics do not seem to induce diabetes or impaired glucose tolerance when used in small doses. At higher doses and in elderly patients impairment of glucose tolerance might appear. The commonly encountered hypokalemia during diuretic treatment seems to be related to the dose and to the duration of the diuretic action. Diuretics can always be used once daily, and they are cheaper than beta-blockers, even when a greater need for laboratory check-ups is taken into account. While beta-blockers so far have not been shown to prevent or postpone hypertensive complications, diuretics have done so in several recent large-scale trials. Two multicenter trials are currently testing the hypothesis of whether beta-blockers are superior to diuretics in preventing coronary heart disease, the most common hypertensive complication. Until these studies are presented, there is little evidence to change the current use of diuretics as first-choice drugs in hypertension.

Adrenergic beta-Antagonists↗
PubMed1984

Effects of treatment with diuretics on serum lipoproteins.

Diuretics, when used for antihypertensive therapy, may also affect lipoprotein metabolism. The following observations were made after 1-12 months of treatment. Various thiazide-type diuretics significantly increased the potentially atherogenic serum low-density lipoprotein cholesterol (LDL-C) and/or very-LDL-C (V-LDL-C) fractions, while the antiatherogenic high-density lipoprotein cholesterol (HDL-C) level was largely unchanged. Certain loop diuretics also increased the LDL-C/HDL-C ratio. Both types of diuretics elevated serum triglyceride (Tg) levels in some, but not all, studies. Levels of LDL-C were increased in diuretic-treated men and in chlorthalidone-treated postmenopausal women, but not in chlorthalidone-treated premenopausal women. Only two diuretics evaluated, indapamide and spironolactone, had no apparent influence on lipoproteins. A tendency for increased Tg levels and lower HDL-C concentrations was apparent during combined thiazide-type diuretic-beta-blocker treatment; these changes resembled those observed during beta-blocker monotherapy. Diuretic-induced increases in LDL-C were prevented or reversed by concomitant beta-blockade, but not by combination treatment with sympatholytics such as reserpine, methyldopa, and clonidine. Prospective studies are needed to clarify the long-term course and the pathogenic and prognostic relevance of lipoprotein changes induced by various diuretics. In the meantime, it is of clinical interest that premenopausal women may be protected from thiazide-induced increases in LDL-C, certain diuretic agents have no significant effect on serum lipoproteins, and beta-blockers may prevent or reverse increases in LDL-C in men and postmenopausal women during diuretic treatment.

Adolescent↗
PubMed1997

Withdrawal of long-term diuretic medication in elderly patients: a double blind randomised trial.

OBJECTIVES: 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. DESIGN: Double blind randomised controlled trial with six month follow up. SETTING: General practice. SUBJECTS: 202 patients taking long-term diuretics without manifest heart failure or hypertension. INTERVENTIONS: Patients were allocated to either placebo (withdrawal group, n = 102) or continuation of diuretic treatment (control group, n = 100). MAIN OUTCOME MEASURE: Occurrence of clinical conditions requiring diuretic therapy based on fixed criteria. RESULTS: 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. CONCLUSION: 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.

Aged↗
PubMed1985

Diuretics. Clinical pharmacology and therapeutic use (Part I).

25 years have elapsed since the introduction of the first effective oral diuretic, chlorothiazide. Diuretics are now amongst the most widely prescribed drugs in clinical practice worldwide. Availability of these drugs has not only brought therapeutic benefit to countless numbers of patients but it has at the same time provided valuable research tools with which to investigate the functional behaviour of the kidney and other electrolyte-transporting tissues. Despite many remaining gaps in our knowledge of the biochemical processes involved in diuretic drug action, available compounds can be divided into 5 groups on the basis of their preferential effects on different segments of the nephron involved in tubular reabsorption of sodium chloride and water. Firstly, there is heterogeneous group of chemicals that share the common property of powerful, short-lived diuretic effects that are complete within 4 to 6 hours. These agents act on the thick ascending limb of Henle's loop and are known as 'high ceiling' or 'loop' diuretics. The second group are the benzothiadiazines and their many related heterocyclic variants, all of which localise their effects to the early portion of the distal tubule. The third group comprises the potassium-sparing diuretics which act exclusively on the Na+-K+/H+ exchange mechanisms in the late distal tubule and cortical collecting duct. The action of drugs in groups 2 and 3 is prolonged to between 12 and 24 hours. The fourth group consists of diuretics that are chemically related to ethacrynic acid but have the unusual property of combining within the same molecule the property of saluresis and uricosuria. These compounds have actions, to different individual extents, in the proximal tubule, thick ascending limb, and early distal tubule and are known as 'polyvalent' diuretics. Finally, there is a mixed group of weak or adjunctive diuretics which includes the vasodilator xanthines such as aminophylline, and the osmotically active compounds such as mannitol. Available evidence on the molecular mechanisms of action of diuretics in each group is reviewed. The haemodynamic, humoral and physical factors involved in control of electrolyte and fluid handling by the kidney in normal conditions and pathological states are discussed in relation to rational choices of different diuretics in the treatment of various oedematous and non-oedematous conditions.

Animals↗
PubMed1985

Resistance to loop diuretics. Why it happens and what to do about it.

Resistance to loop diuretics is often encountered clinically. Studies in healthy subjects have shown that overall response to loop diuretics depends upon the interplay between the total amount of drug reaching the urine, the time course of its entry into urine and the pharmacodynamics of response to diuretic in the urine. The mechanism by which diuretic resistance occurs has been elucidated in several clinical conditions. Treatment with inhibitors of prostaglandin synthesis has no effect on diuretic appearance in urine but blunts response by blocking the increase in renal blood flow produced by loop diuretics. In the elderly and in patients with moderate renal insufficiency, the mechanism of resistance appears to be purely pharmacokinetic, involving altered access of diuretic into the urine. In contrast, patients with nephrotic syndrome and hepatic cirrhosis manifest a purely pharmacodynamic form of resistance: in nephrosis, diuretic may bind to protein in the urine; in cirrhosis the mechanism of resistance is unclear. Lastly, in patients with congestive heart failure, with intravenous administration, resistance represents a pharmacodynamic phenomenon. With oral administration, however, the time course but not the extent of absorption is altered; consequently, in this setting, both pharmacokinetic and pharmacodynamic changes may contribute to the subnormal response. Strategies for overcoming resistance to loop diuretics in patients receiving NSAIDs or those with renal disease, hepatic cirrhosis or congestive heart failure include one or more of: increasing the dose size; administering frequent 'small' (but effective) doses; continuous intravenous infusion of the diuretic; or concomitant administration of another diuretic such as metolazone or hydrochlorothiazide.

Anti-Inflammatory Agents↗
PubMed1998

Combination diuretic therapy in severe congestive heart failure.

Severe congestive heart failure (CHF) is often characterised by fluid retention. A (chronic) state of overhydration has a negative influence on both the quality of life and prognosis of these patients. Therefore, the use of diuretics remains a cornerstone in the treatment of heart failure. However, diuretic resistance, a failure to correct the hydration state adequately with the use of conventional dosages of loop diuretics, is a frequently occurring complication in the treatment of advanced stages of CHF. Several intra- and extrarenal mechanisms may be involved in the development of diuretic resistance. An important pathophysiological mechanism leading to diuretic resistance seen after chronic use of loop diuretics is the functional adaptation of the distal tubule. Studies in animals demonstrate that the sodium reabsorption capacity of this nephron segment increases significantly when the sodium delivery to this segment is augmented, as is the case during administration of loop diuretics. The use of combinations of diuretics acting on different segments of the nephron appears to be an effective option in the treatment of diuretic resistance. Several combinations have been used; however, the combination of a loop diuretic and a thiazide drug acting on the distal tubule appears to be the most effective. However, since the use of this combination may lead to serious adverse effects such as hypokalaemia, metabolic alkalosis and dehydration, careful monitoring of the patient of combination diuretic therapy is necessary.

Diuretics↗
PubMed2000

[Cardiac insufficiency: what treatment? what dose? For which patients? Converting enzyme inhibitors and diuretics].

Diuretics were the first family of drugs to be used in cardiac failure. They improve symptoms but no randomised control trials show their efficacy in prolonging survival. The results of the recent RALES trial, however, provides evidence in favour of antialdosterone diuretics on survival in association with a loop diuretic and an angiotensin converting enzyme inhibitor. At present, the legal requirements in France state that "the association of spironolactone and converting enzyme inhibitors is possible with low doses of angiotensin converting enzyme inhibitors and diuretic hypokalaemiant; kalaemia and creatinine have to be monitored". "The association of hypokalaemia-inducing diuretics (loop diuretics, thiazides and similar: the association with this type of diuretic, rational and useful in certain patients, does not exclude the risk of hypo- or even hyperkalaemia, especially in renal failure and diabetes; it also imposes the monitoring of serum potassium and eventually of the electrocardiogram and, if necessary, to reconsider the treatment". Many points remain unclear concerning the value and harmlessness of the prescription of diuretics in asymptomatic left ventricular failure. In cases of diuretic resistance, the use of intravenous administration, the fragmentation of doses or the association of diuretics, may induce a diuretic response. Angiotensin converting enzyme inhibitors are the first line treatment of moderate and severe cardiac failure and in post-infarction left ventricular dysfunction. On the other hand, the value of this family of drugs in left ventricular failure and normal systolic function has not been demonstrated. Analysis of clinical practice shows an underprescription of angiotensin converting enzyme inhibitors, both in number of patients and in dosage. The results of the recent ATLAS trial suggest that high doses of lisinopril improve morbidity related to cardiac failure and the combined morbi-mortality criterion. The results of this study incite the prescription of high rather than low doses of angiotensin converting enzyme inhibitor.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Diuretic therapy in congestive heart failure.

The principal goals of treatment of the patient in heart failure are the relief of their symptoms and improvement in their prognosis. Of all antiheart failure drugs currently available, the diuretics are therapeutically superior in their efficacy in relieving clinical symptoms and signs. Whether administered intravenously or orally, all diuretics result in a substantial reduction in the raised pulmonary vascular pressures in combination with a small reduction in cardiac output. Diuretics stimulate release of renin with subsequent activation of the renin-angiotensin-aldosterone system, particularly if used in large doses, although their quantitative impact on the neuroendocrine profile at different stages of heart failure remains to be defined. In patients with mild heart failure, diuretics reduce plasma catecholamine concentrations, but their sympatholytic effects in more severe cases are unknown, as are their effects on the metabolically active tissues in these patients. Diuretic resistance can be circumvented by segmental nephron blockade with a combination of low-dose diuretics that simultaneously block sodium reabsorption in the proximal tubule, the loop of Henle, the distal tubule, and the collecting duct. Diuretics improve symptoms of breathlessness and signs of peripheral edema in patients with congestive heart failure in direct relationship to the induced diuresis. These benefits are frequently associated with a substantial improvement in patients' appreciation of quality of life and economic capacity. There are few adverse reactions to chronic diuretic therapy, but the serum electrolytes should be monitored for hypokalemia and hypomagnesemia. The impact of diuretics on prognosis of patients with congestive heart failure is unknown; however, diuretics have been a major ingredient of the therapies used in all the survival trials with vasodilators, angiotensin-converting enzyme inhibitors, and beta-blocking drugs. In addition to their clinical benefits, diuretics are the most cost-effective treatment of any single drug group currently available for the treatment of patients with congestive heart failure.

Adult↗
PubMed1985

Diuretics in cardiovascular therapy. Perusing the past, practising in the present, preparing for the future.

Diuretics are the mainstay of drug therapy in the treatment of many cardiovascular disorders. However, perusal of knowledge of their haemodynamic activities in heart failure and hypertension reveals major gaps. In left ventricular failure complicating acute myocardial infarction, intravenous frusemide reduces the elevated left heart filling pressure with little change in systemic blood pressure, heart rate or cardiac output, and restores the ability of the left heart to handle an acute increase in filling volume. But there is little knowledge of the haemodynamic effects of other intravenous diuretics, oral diuretics or diuretics other than those acting on the loop of Henle in this emergency clinical situation. Even less information is available on the haemodynamic effects of diuretics in patients in chronic heart failure. In patients with valvular heart disease, parenteral mercury and oral thiazides reduce right heart and pulmonary vascular pressures with variable (dose-dependent?) changes in cardiac output. Information on the effect of loop diuretics, the comparative effects of intravenous versus oral routes of administration and dose-response correlations are all lacking. In hypertension, the dose-blood pressure lowering response relationship of orally administered diuretics is relatively flat. The majority of information relates to oral thiazides; there is little reliable information on the anti-hypertensive efficacy of the loop diuretics. The acute and chronic effects of the majority of commonly used diuretics on cardiac and peripheral vascular functions is unexplained. More is known of their potentially adverse metabolic effects than of their possible circulatory benefits in hypertensive patients. Many unwanted side-effects of these drugs have been described; their potential importance is related directly to the disease state and doses in which they are used. In acute heart failure, their potential danger is probably minimal. In the treatment of chronic heart failure their most sinister potential is in the excessive secretion of potassium and magnesium. In hypertensive patients their long-term administration in high-doses may lead to undesirable metabolic effects that tend to offset their blood pressure lowering activity. Despite their drawbacks, diuretics continue to provide the natural first-line treatment of choice of these common cardiovascular syndromes. But more information on their mechanisms of vascular activities and the differences in non-diuretic activity between different compounds is urgently required.

Angina Pectoris↗
PubMed1994

Diuretic treatment for the sodium retention of congestive heart failure.

The use of diuretics for the treatment of sodium retention in congestive heart failure was evaluated. Particular focus was given to the altered renal response to diuretics in patients with heart failure and adverse responses to diuretic therapy. Highlighted information included historical aspects of the development of diuretics, mechanisms of sodium retention, the physiologic and clinical response to diuretics, and the altered pharmacokinetics and pharmacodynamics of diuretics in congestive heart failure. Despite more than 60 years of empiric diuretic use in heart failure, the actual database regarding the long-term efficacy, adverse effects, and altered mortality outcome in heart failure is relatively small. Existent pharmacokinetic and pharmacodynamic data are typically not collected within the context of heart failure efficacy trials. In addition to altered electrolyte transport and total-body electrolyte depletion, diuretics may be associated with adverse neurohormonal activation. Thus, guidelines for acute and long-term therapy with diuretics in heart failure remain somewhat empiric. Diuretics will remain a mainstay for the treatment of edema in congestive heart failure but must be accompanied by moderate sodium restriction. However, large clinical trials of diuretics would be necessary to demonstrate that improved clinical efficacy with edema reduction is not offset by adverse effects, which include electrolyte depletion, ventricular arrhythmias, and subsequent increased mortality.

Administration, Oral↗
PubMed1995

Non-potassium-sparing diuretics and risk of sudden cardiac death.

OBJECTIVE: To review current evidence for a possible association between the use of non-potassium-sparing diuretics and the risk of sudden cardiac death in hypertension. METHODS: Examination of published randomized trials and recent case-control studies. RESULTS: Numerous studies have shown that the administration of non-potassium-sparing diuretics causes a dose-dependent decrease in serum potassium levels in hypertensive patients. Although largely circumstantial, some evidence implies that diuretic-induced electrolyte depletion leading to arrhythmias may be the mechanism involved in the association between diuretics and sudden death. Published randomized trials on the efficacy of non-potassium-sparing diuretic therapy have consistently failed to show a reduction in the incidence of sudden cardiac death, while findings from hypertension trials including potassium-sparing diuretic combinations demonstrated an impressive decrease in coronary events. Two similar, recent case-control studies, together comprising 371 cases of sudden cardiac death in patients taking drug treatment for hypertension, indicated that hypertensive patients who were prescribed non-potassium-sparing diuretics had approximately double the risk of sudden cardiac death compared with users of potassium-sparing diuretic therapy. Although treatment allocation in these studies is, by definition, non-random, adequate measures were taken to reduce sources of bias. CONCLUSIONS: Current evidence supports the hypothesis that diuretic-induced potassium loss causes sudden cardiac death in some hypertensive patients. It seems prudent to use thiazide diuretics at a low dose only. Adding a potassium-sparing diuretic drug may further reduce the mortality risk.

Benzothiadiazines↗
PubMed1998

Do diuretics differ in terms of clinical outcome in congestive heart failure?

Diuretics are required in the majority of patients with symptomatic congestive heart failure (CHF). The reduction of pulmonary venous congestion results in rapid improvement of dyspnoea and increased exercise tolerance. In contrast to arterial hypertension, there are only a few studies comparing diuretics with other drugs in CHF. In particular, no reliable data exist on the effect of diuretics on mortality and major cardiac events in CHF. Diuretic agents differ in their mode of action, pharmacodynamics and pharmacokinetic properties. Loop diuretics are used in acute CHF and in severe chronic CHF, while thiazides, having a longer duration of action, are suitable for long-term therapy of mild CHF in ambulatory patients. Potassium-sparing diuretics are usually prescribed in combination with other preparations to prevent electrolyte disturbances. No randomized prospective large-scale trials have been carried out to compare the efficacy and tolerability of the various types of diuretics. With adequately chosen dosage, the effects of the different loop diuretics appear to be similar in CHF. However, observational data in ambulatory patient populations indicate that loop diuretics with high bioavailability and longer half-life may offer advantages in terms of clinical stability and resource utilization for cardiac decompensation. In patients with severe pulmonary congestion and oedema, combined use of loop diuretics and thiazides may improve the therapeutic response. Spironolactone can also be prescribed to increase diuresis in patients who are resistant to a combination of loop diuretics and ACE inhibitors.

Diuretics↗
PubMed1998

NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics.

BACKGROUND: Both diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used, in particular among the elderly. The use of NSAIDs may decrease the efficacy of diuretics and induce congestive heart failure (CHF) in patients treated with diuretics. OBJECTIVE: To investigate the risk of CHF associated with combined use of diuretics and NSAIDs in patients older than 55 years. METHODS: We conducted a study in a base cohort of 10,519 recipients of diuretics and NSAIDs identified in the PHARMO database during the period from 1986 through 1992. The incidence density of hospitalizations for CHF during exposure to both diuretics and NSAIDs (index) was compared with that during exposure to diuretics only (reference). RESULTS: We found an overall increased risk of hospitalization for CHF during periods of concomitant use of diuretics and NSAIDs compared with use of diuretics only (crude relative risk, 2.2; 95% confidence interval, 1.7-2.9). After adjusting for cofactors including age, sex, history of hospitalization, and drug use, a 2-fold increased risk remained (relative risk, 1.8; 95% confidence interval, 1.4-2.4). CONCLUSION: Use of NSAIDs in elderly patients taking diuretics is associated with a 2-fold increased risk of hospitalization for CHF, especially in those with existing serious CHF.

Aged↗