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At least 253 records · Page 14Linked to original sources
PubMed1993

Effects of thiazide diuretic therapy on bone mass, fractures, and falls. The Study of Osteoporotic Fractures Research Group.

OBJECTIVE: To determine the relation between the use of thiazide diuretics and bone mass, fractures, and falls in older women. DESIGN: Cross-sectional study of thiazide diuretics, bone mass, and prevalent vertebral deformities; cohort analysis of thiazide diuretics and nonspinal fractures and falls. SETTING: Four clinical centers located in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela Valley, Pennsylvania. PARTICIPANTS: A total of 9704 ambulatory, nonblack women who were 65 years or older. MEASUREMENTS: Information on thiazide use, demographic data, medical history, and anthropometric measurements were obtained by questionnaire, interview, and examination. Appendicular bone mass was measured by single-photon absorptiometry. Incident falls and fractures were ascertained every 4 months. RESULTS: Women using thiazide diuretics for more than 10 years had significantly higher bone mass than women who had never used thiazide diuretics (for example, 0.381 g/cm2 compared with 0.355 g/cm2 for the distal radius [P < 0.001]). Current users of thiazide diuretics had an incidence of falls (relative risk, 1.06; 95% CI, 0.90 to 1.25) that was similar to that of those who had never used these drugs. After adjusting for age, body weight, functional status, total calcium intake, duration of estrogen replacement therapy, and self-reported health status, we found that current users of thiazide diuretics who had taken these drugs for more than 10 years had a risk for nonspinal (relative risk, 0.99; CI, 0.81 to 1.20) and osteoporotic (relative risk, 0.98; CI, 0.79 to 1.22) fractures that was similar to that of women who had never used thiazides; however, thiazide users did have a lower risk for fractures of the hip (relative risk, 0.63; CI, 0.34 to 1.16) and wrist (relative risk, 0.66; CI, 0.40 to 1.08), neither of which was significant. CONCLUSIONS: Thiazide diuretics have no effect on a women's risk for falling or for experiencing nonspinal fractures. The trend toward a lower risk for hip and wrist fractures is consistent with findings in previous cohort studies but may reflect selection factors for the use of thiazide diuretics. A randomized trial is needed to determine the effect ot thiazide diuretics on the incidence of fractures.

Accidental Falls↗
PubMed1987

Comparison of calcium-entry blockers and diuretics in the treatment of hypertensive patients.

This review compares the calcium antagonists with diuretics in the management of mild-to-moderate essential hypertension. The antihypertensive efficacy of calcium antagonists appears comparable to that of oral diuretics such as hydrochlorothiazide when used as monotherapy. Peripheral vascular dilation appears to be the principal mechanism of the long-term blood pressure-lowering effects of both calcium antagonists and diuretics. Peripheral vasoconstrictor responses to cardioreflex-mediated sympathetic nervous system activation is attenuated by calcium antagonists but not by diuretics. Long-term calcium antagonist therapy is generally not associated with reflex activation of the sympathetic nervous system or of the renin-angiotensin-aldosterone axis, whereas diuretic therapy results in considerable activation of the renin-angiotensin-aldosterone system. Calcium antagonists appear to have a greater beneficial effect than diuretics with respect to maintenance of renal blood flow and glomerular filtration rate. Calcium antagonists, because of their effects on coronary blood flow and heart rate-blood pressure product, offer advantages over diuretics in the treatment of hypertensive patients with concomitant ischemic heart disease. Metabolic abnormalities associated with diuretic antihypertensive therapy, such as hypokalemia, hypercalcemia, hyperuricemia, lipid changes, and hyperglycemia, are generally not observed with calcium antagonists. Many of these deleterious metabolic changes observed with diuretic therapy may be minimized by the use of smaller doses of these agents than have generally been employed in the past. Diuretics are less expensive and require less frequent dosing than calcium antagonists. Thus, they continue to be preferable first-line antihypertensive agents in many patients with mild-to-moderate hypertension.

Calcium Channel Blockers↗
PubMed1983

Diuretic use in an ambulatory elderly population.

The nature and extent of diuretic use and the effect of diuretics on clinical laboratory values were studied in a retirement community. Study participants completed health questionnaires and provided information on all prescription and nonprescription medications regularly used. Subjects using diuretics were categorized according to product(s) used; a control group used no diuretics. Results for diuretic users who used potassium supplements were analyzed separately. Data were collected on 2009 women and 1183 men over 65 years old. At least one diuretic drug was used by 40.2% of the women and 29.5% of the men. In most cases, the diuretic was used daily (81.1%) and had been used for longer than two years (72.5%). Approximately one third of the subjects had hypertension. Serum potassium values for users of chlorthalidone and thiazide diuretics showed the greatest difference from the control group, while users of the combination of hydrochlorothiazide and spironolactone showed the greatest difference in serum sodium concentrations. Particularly in furosemide users, uric acid, BUN, and creatinine concentrations were significantly different from control. When serum potassium values of subjects using both diuretics and potassium supplements were analyzed, values were lower in participants using supplements. In many cases, significantly different laboratory values were still within normal limits. Long-term diuretic use in this ambulatory elderly population was high and was associated with numerous alterations in biochemical values.

Aged↗
PubMedDate not supplied

Withdrawing long-term diuretic therapy in the elderly: a study in general practice in The Netherlands.

BACKGROUND: About 20% of all men and women age 65 or older are on maintenance therapy with diuretics. Multiple drug use and side effects increase with age whereas a clear indication for long-term diuretic therapy is not always present. The aim of the present study was to assess whether in some patients long-term diuretic therapy could be withdrawn in general practice. METHODS: This study is a pilot-study for a large multicentered randomized controlled trial in general practice. In one general practice in The Netherlands, 15 diuretic-using patients were selected from a total population of 52. All had been using diuretics for more than six months, were not hypertensive, and did not show overt symptoms of heart failure. In these 15 patients, diuretic medication was withdrawn under careful medical monitoring conditions. RESULTS: After six months, six patients were still without diuretic therapy. Diuretic therapy had to be resumed in nine cases, because of congestive heart failure (one), hypertension (three), bronchial asthma (one), increased ankle edema (two) and subjective complaints (two). The withdrawal of diuretic therapy caused an increase in mean systolic blood pressure, heart failure score, body weight and ankle edema. CONCLUSIONS: Long-term maintenance diuretic therapy in patients age 65 or older in general practice may be successfully withdrawn in selected cases. Careful medical surveillance during and after withdrawal is warranted.

Aged↗
PubMed1993

Interaction of thiazide and loop diuretics with the basolateral para-aminohippurate transport system in isolated S2 segments of rabbit kidney proximal tubules.

The effect of thiazide and loop diuretics on the tubular uptake of [3H]para-aminohippurate ([3H]PAH), a marker of the organic anion transport system, was tested in vitro on single S2 segments of the proximal tubule of rabbit kidneys. Because the tubules were not perfused, and hence were collapsed, the tubular [3H] PAH uptake reflects [3H]PAH transport across the contraluminal membrane. The diuretics were added to the bath solution in at least six different concentrations. The concentration of [3H]PAH in the bath solution amounted to 1.3 mumol/l, and was 12 times lower than the PAH concentration (16 mumol/l) at half-maximum PAH uptake. The results show that all of the nine diuretics tested inhibited [3H]PAH uptake. The IC50 values of the individual drugs ranged from 3 to 400 mumol/l. In general, thiazide diuretics had a lower affinity to the PAH transporter than loop diuretics. This probably results from differences in the pKa values which range from 3.6 to 4.1 for the loop diuretics and from 9.2 to 10 for the thiazide diuretics. Furthermore, there was a highly significant dependence of affinity on the hydrophobic properties of the diuretics. At concentrations 10- to 100-fold lower than the IC50 values all diuretics stimulated [3H]PAH uptake which may indicate a positive cooperative interaction of these drugs with the PAH transporter. Within the group of loop diuretics the order of the affinity to the PAH transporter and to the Na, 2 Cl, K cotransporter in the thick ascending limb of Henle's loop was identical.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

[Diuretics].

Diuretics have been empirically developed. Inorganic mercury was used as diuretics from 16C. Guy's Hospital Pills (containing the equal part of Hg2Cl2, digitalis, and squill) was well known in the 19 C. Discovery of the diuresis of merbaphen has led to develop many organomercurial diuretics and to give suggestion of the drug design of ethacrynic acid. Diuresis in patients given sulfonamide was discovered in 1938. Inhibition of carbonic anhydrase by sulfonamide was related to its diuresis. Drug design aimed to enhance the inhibition of this enzyme has obtained acetazolamide, then chlorothazide. But, the discovery of remarkably enhanced diuretic activity (decreased inhibition on the enzyme) of hydrochlorothazide changed this drug design to rondom chemical modification of thiazide ring. Then, furosemide and other loop diuretics were obtained. The structure-activity relationship of thiazides using the electronic state and other physico-chemical indices was studied by us. A large hydrophobic center linked to a positive formal charge was assumed to the receptor of thiazide. Binding of thiazide to erythrocyte which gives mild and long acting diuretic property was found by us. Recently, shut down of the tubuloglomerular feedback by loop diuretics was reported. Loop diuretics are metabolized to loss their activity. Therapeutic drug monitoring is necessary to obtain a desirable diuresis. By wide clinical use of thiazides and loop diuretics, patients with hyponatremia with eu-or hypervolemic increased. I have proposed aquaretics since 1976. In 1992, nonpeptide selective vasopressin V2 receptor antagonist (OPC-31260) was first synthesized in Japan. This has been found to cause hypotonic diuresis and elevation of serum Na level in men. The combined use of loop diuretics and aquaretics should be considered.

Animals↗
PubMed1996

The effects of diuretics on quality of life of hypertensive patients.

OBJECTIVES: To study the effect of diuretics and diuretics discontinuation on the quality of life (QOL) of hypertensive patients. METHODS: 149 beta blocker treated mild to moderate hypertensive patients were included in the study. Seventy-three were treated by beta blockers (BB's) only and 60 by BB's and diuretics, for 40 patients diuretics was discontinued. Physical symptoms and QOL were assessed before and 9-15 months after the change in treatment. RESULTS: At baseline, subjects on diuretics experienced more gastrointestinal symptoms, weakness, and sex related problems; and their QOL was poorer. At the end of the follow-up, patients on diuretics scored poorest on physical strength items and on health perceptions; those who were never treated by diuretics scored best; and those who stopped were in between. CONCLUSIONS: Diuretics treatment adversely affect patients' QOL. Cessation of diuretics treatment for at least 9 months improved some aspects of patients' QOL, though those who never received diuretics were better of than others.

Adrenergic beta-Antagonists↗
PubMed1996

Molecular cloning and function expression of a diuretic hormone receptor from the house cricket, Acheta domesticus.

Insect diuretic hormones regulate fluid and ion secretion and the receptors with which they interact are attractive targets for new insect control agents. Recently, a diuretic hormone receptor from the moth Manduca sexta was isolated by expression cloning and found to be a member of the calcitonin/secretin/corticotropin releasing factor family of G-protein coupled receptors [Reagan J. D. (1994) J. Biol. Chem. 269, 9-12]. Degenerate oligonucleotides were designed based upon conserved regions in this receptor family and used to isolate a diuretic hormone receptor from the house cricket, Acheta domesticus. The complementary DNA isolated encodes a protein consisting of 441 amino acids with seven putative membrane spanning regions. Interestingly, unlike the M. sexta diuretic hormone receptor, the cricket diuretic hormone receptor contains a putative signal sequence. The receptor shares 53% and 38% sequence identity with the M. sexta diuretic hormone and human corticotropin releasing factor receptors respectively. When expressed in COS-7 cells, the receptor binds A. domesticus diuretic hormone with high affinity and stimulates adenylate cyclase with high potency. Four other insect diuretic hormones are considerably less effective at stimulating adenylate cyclase in COS-7 cells transfected with the receptor. This is in contrast to the M. sexta diuretic hormone receptor which is stimulated by all five insect diuretic hormones with high potency.

Amino Acid Sequence↗
PubMed1996

Effects of diuretic therapy on the development of tolerance to nitroglycerin and exercise capacity in patients with chronic stable angina.

BACKGROUND: Therapy with diuretics has been reported to prevent the development of nitrate tolerance. Importantly, diuretics may have independent antianginal effects through their effects on intravascular volume. The present investigation was designed to determine whether diuretic therapy could prevent the development of tolerance to continuous transdermal nitroglycerin. The study was also designed to examine whether diuretic therapy has an independent antianginal effect. METHODS AND RESULTS: Twelve patients with chronic stable angina were studied in a randomized, double-blind, crossover trial. Patients received diuretic (hydrochlorothiazide plus amiloride) or placebo for 14 to 20 days. During each double-blind treatment period, patients underwent treadmill exercise testing on three separate occasions. The first exercise testing was performed after 7 to 10 days of single-blind, placebo transdermal nitroglycerin therapy. Subsequently, exercise testing was repeated on the first day of active transdermal nitroglycerin therapy and following 7 to 10 days of continuous transdermal nitroglycerin application. Therapy with a diuretic was associated with an increase in exercise capacity but had no effect on nitroglycerin tolerance. During therapy with placebo transdermal nitroglycerin, diuretic therapy caused an increase in treadmill walking time to the development of moderate angina compared with placebo (371 +/- 26 versus 288 +/- 16 seconds, diuretic versus placebo, P < .01). Similar results were obtained during both acute and sustained nitroglycerin therapy. CONCLUSIONS: The results of this study demonstrate that therapy with a diuretic has no effect on the development of tolerance to continuous transdermal nitroglycerin. Interestingly, diuretic therapy itself has important antianginal effects and improves exercise capacity in patients with stable angina.

Administration, Cutaneous↗
PubMed2005

Thiazide diuretics and the risk of gallbladder disease requiring surgery in women.

BACKGROUND: Previous studies have suggested that thiazide diuretic use increases the risk of cholecystitis. METHODS: We prospectively examined the association between thiazide use and cholecystectomy, a surrogate for symptomatic cholelithiasis, in a cohort of 81 351 US women who were aged 30 to 55 years in 1980 and followed up to 2000. Regular use of thiazide diuretics was assessed at baseline by asking the participants to report whether they currently took "any of the following medications in most weeks" and listing "thiazide diuretics (eg, Diuril and Hydrodiuril)" among other drugs. Respondents were also requested to report the duration of thiazide diuretic use. Assessment of thiazide diuretic use was updated in 1982, 1988, 1994, 1996, and 1998. Cox regression was used to adjust simultaneously for other potential risk factors for cholecystectomy. RESULTS: During follow-up, 8607 women reported undergoing a cholecystectomy. A modest positive relation between the use of thiazide diuretics and cholecystectomy was observed. Compared with never users of thiazide diuretics, the multivariate relative risk of cholecystectomy for past users was 1.16 (95% confidence interval,1.08-1.24) and the multivariate relative risk for current users was 1.39 (95% confidence interval, 1.29-1.50). CONCLUSIONS: These findings are compatible with the hypothesis that the use of thiazide diuretics increases the risk of symptomatic cholecystitis. However, we cannot rule out the possibility that our results are in part explained by unconsidered factors related to the indication for antihypertensive therapy or by differences in medical surveillance between users and nonusers of thiazide diuretics.

Adult↗
PubMed1998

Why are physicians not prescribing diuretics more frequently in the management of hypertension?

Diuretics have again been recommended by the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) as one of the first-choice medications in the management of hypertension. This recommendation is based on the results of numerous randomized, diuretic-based, long-term controlled clinical trials that have demonstrated a reduction in both cerebrovascular and cardiovascular morbidity. Despite this and other national recommendations, the use of diuretics has steadily decreased over the past 15 years. Reasons include heavy promotion of other medications and the perception that diuretics produce adverse metabolic effects and do not reduce coronary heart disease events. Data, however, indicate that (1) changes in glucose and cholesterol metabolism are minor, especially with the smaller doses now being used; (2) cardiovascular morbidity and mortality have been reduced in hypertensive patients, even in those with hyperlipidemia or diabetes, when diuretics are used; and (3) concerns about hypokalemia-induced arrhythmias have been overstated. While special indications exist for other medications in the treatment of hypertension, for example, use of an angiotensin-converting enzyme inhibitor (usually in addition to a diuretic) for a patient with heart failure or diabetic nephropathy, most patients, including those with hyperlipidemia or glucose intolerance, can be effectively treated with a diuretic as initial therapy or as part of a combination regimen. Diuretics should be used more not less frequently; use of diuretics would reduce the number of resistant hypertensive patients.

Antihypertensive Agents↗
PubMed1993

Low-dose segmental blockade of the nephron rather than high-dose diuretic monotherapy.

The specific renal effect of diuretics is due to the fact that their concentrations is almost 100-fold greater in the renal tubule than in the plasma. The function of the different segments of the nephron may be altered following changes in the effective arterial blood volume (EABV) and the extracellular fluid volume (ECFV). In diseases with reduced EABV, e.g., congestive heart failure, decompensated cirrhosis of the liver, and the nephrotic syndrome, proximal tubular hyperreabsorption of sodium occurs, leaving only a low Na+ load in the distal segments of the nephron, the site of diuretic action. Clinically, the response to diuretics is reduced or resistance to diuretics may even ensue, which can be predicted by a FENa < 0.2%. Resistance to diuretics can be overcome by short-term comedication with acetazolamide, which increases Na+ delivery to the site of action of the other diuretics used concomitantly. In states with increased ECFV, e.g. in chronic renal failure, there is distal tubular Na+ rejection, leading to a greater increase in FENa the more GFR is reduced. The remaining intact nephrons present a relatively increased response to diuretics. The efficacy of diuretic treatment in renal failure can be optimised by combining loop diuretics with thiazides. In conclusion, low-dose combination therapy, inducing "segmental blockade of the nephron", meets the functional changes along the nephron. It is therefore more effective and safer than high-dose monotherapy.

Diuretics↗
PubMed2004

[Modern differential therapy with diuretics].

Diuretics block different electrolyte transporters in renal tubular cells. Their predominant action is inhibition of renal sodium chloride reabsorption, however, and achievement of a negative body sodium balance is the principal goal of diuretic therapy in patients with hypertension and edema. Several classes of diuretics can be distinguished with respect to the sites of sodium reabsorption along the nephron, but loop diuretics and distal-tubular diuretics (incl. thiazides) are the most widely used. The latter have a less potent natriuretic effect than loop diuretics, but their long duration of action predispose them for treatment of patients with uncomplicated hypertension. In conditions of gross edema, e.g. heart and/or renal failure, distal-tubular diuretics lose their efficacy and must be replaced by or combined with loop diuretics ("sequential nephron blockade"). Aldosterone antagonists are unique among diuretics because they improve survival in patients with heart failure independently of their effect on sodium metabolism.

Benzothiadiazines↗
PubMed1998

Loop diuretics in patients aged 75 years or older: general practitioners' assessment of indications and possibilities for withdrawal.

OBJECTIVE: To examine the indications for prescription and possibilities for withdrawal of loop diuretics in community-dwelling patients aged 75 years or older, as reported by their general practitioners (GPs). METHODS: Analysis of dispensary data to identify patients aged 75 years or older using loop diuretics on 1 February 1996. Questionnaires were sent to the GPs of these patients to inquire about the indications for loop diuretic prescription and the necessity for continuation. We subsequently determined loop diuretic prescription rates in the survey population over the next 9 months. SETTING: A panel of nine Dutch community pharmacies. RESULTS: Questionnaires were returned for 338 out of 667 patients (50.7%) using loop diuretics on 1 February 1996. Reported indications for loop diuretic use were heart failure in 223 patients (66.0%), hypertension in 35 patients (10.4%), and a combination of both in 23 patients (6.8%). Loop diuretics were used for ankle edema in 27 patients (8.0%) and for unknown reasons in another 27 patients (8.0%). Continuation of treatment was considered unnecessary by GPs in 66 out of 338 patients (19.5%). However, prescription rates for these 66 patients in the following months were no different from rates for the remaining 272 patients. Loop diuretics were still prescribed to 47 of 66 patients (71.2%) after 12 weeks, and to 26 patients (39.4%) after 36 weeks. CONCLUSIONS: GPs reported substantial opportunities for withdrawal of loop diuretics in patients over 75 years of age, but this did not influence actual prescription rates in these patients. Future studies should explore means of facilitating withdrawal of these medications in this population.

Age Factors↗
PubMed1987

Identification of normal neurohormonal activity in mild congestive heart failure and stimulating effect of upright posture and diuretics.

To characterize further the pathophysiology of the neurohormonal vasoconstrictor pathways in congestive heart failure (CHF), plasma renin activity, plasma norepinephrine, blood pressure, blood volume and renal hemodynamics were measured in 12 patients with mild to moderate CHF. In addition, the response to the gravitational stress of head-up tilt and the influence of 3 weeks of furosemide treatment as stimuli of neurohormonal activity were assessed. Supine plasma renin activity before diuretics was relatively normal at 1.94 +/- 1.6 ng/ml/hr and was significantly increased to 3.9 +/- 2.7 ng/ml/hr after diuretics. During tilt, there was a significant reflex increase in plasma renin activity both before and after diuretics. Plasma norepinephrine was also relatively normal before diuretics (325 +/- 211 pg/ml), did not increase after diuretics, but showed significant increases during tilt both before and after diuretics. Diuretic administration led to decreases in both systolic and diastolic blood pressures, but there was no change in body weight or total blood volume. In addition, diuretic administration did not result in any significant changes of renal blood flow (546 +/- 119 to 634 +/- 204 ml/min/1.73m2), glomerular filtration rate (81 +/- 22 to 90 +/- 27 ml/min/1.73m2) or filtration fraction (0.26 to 0.25). The present study demonstrates that the renin-angiotensin system and the sympathetic nervous system were not activated in the early symptomatic stages of CHF and that baroreceptor stimulation of these pathways during head-up tilt was relatively preserved. Renin secretion increased during diuretic administration, suggesting that the macula densa signal for renin release was also preserved in patients with relatively mild CHF.

Aged↗
PubMed1990

Interaction of diuretics and electrolytes in congestive heart failure.

Diuretic drugs have been the mainstay of treatment for heart failure. Specific elucidation of the effects of diuretics on electrolytes, however, has been difficult, since the heart failure state itself may alter the electrolyte balance. Nevertheless, it is noteworthy that the natriuretic effect of loop diuretics is greater in edematous patients than in healthy volunteers; yet, the initial kaliuresis is minimal--perhaps because aldosterone levels are low. With continued treatment (or after the edema has been cleared), however, the natriuretic action of loop diuretics is less than that seen in controls, but loss of potassium occurs. The addition of a thiazide to a loop diuretic enhances its natriuretic effect. Both loop and thiazide diuretics can induce depletion of magnesium. Potassium-sparing diuretic drugs augment the natriuresis induced by loop or thiazide diuretics but limit or prevent the loss of potassium or magnesium in the urine, at least in the short term. However, potassium-sparing diuretics can exacerbate the development of hyponatremia.

Benzothiadiazines↗
PubMed1984

Effects of diuretics on plasma volume in pregnancies with long-term hypertension.

The purpose of this randomized, prospective study was to investigate the effects of diuretics on plasma volume findings and perinatal outcome in pregnancies complicated by mild long-term hypertension. Twenty patients were in their first trimester and were receiving diuretics at time of entry to the study: Ten patients were allowed to continue their diuretic medication throughout pregnancy (diuretic group), whereas for the other 10 patients, diuretics were discontinued immediately. Plasma volume was serially measured throughout pregnancy with the use of the Evans blue dye-dilution technique. Initial plasma volume was similar in the two groups. However, in the diuretic group, subsequent plasma volume findings at various stages of gestation were markedly reduced when compared to respective plasma volume findings in the other group. In addition, plasma volume expansion was minimal in the diuretic group (mean increase of 18%), whereas it was normal in the other group (mean increase of 52%). Two patients in the diuretic group and one patient in the other group required other antihypertensive medication. There was no difference in perinatal outcome between the two groups. These results suggest that in hypertensive pregnancies, diuretics prevent normal plasma volume expansion without influencing perinatal outcome.

Adult↗
PubMed2006

Relation of loop diuretic dose to mortality in advanced heart failure.

Although loop diuretics are widely used in heart failure (HF), their effect on outcomes has not been evaluated in large clinical trials. This study sought to determine the dose-dependent relation between loop diuretic use and HF prognosis. A cohort of 1,354 patients with advanced systolic HF referred to a single center was studied. Patients were divided into quartiles of equivalent total daily loop diuretic dose: 0 to 40, 41 to 80, 81 to 160, and >160 mg. The cohort was 76% male, with a mean age of 53+/-13 years and a mean ejection fraction of 24+/-7%. The mean diuretic dose equivalence was 107+/-87 mg. The diuretic quartile groups were similar in terms of gender, body mass index, ischemic cause of HF, history of hypertension, and spironolactone use, but the highest quartile was associated with a smaller ejection fraction and lower serum sodium and hemoglobin levels but higher serum blood urea nitrogen and creatinine levels. There was a decrease in survival with increasing diuretic dose (83%, 81%, 68%, and 53% for quartiles 1, 2, 3, and 4, respectively). Even after extensive co-variate adjustment (age, gender, ischemic cause of HF, the ejection fraction, body mass index, pulmonary capillary wedge pressure, peak oxygen consumption, beta-blocker use, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, digoxin use, statin use, serum sodium, blood urea nitrogen, creatinine, hemoglobin, cholesterol, systolic blood pressure, and smoking history), diuretic quartile remained an independent predictor of mortality (quartile 4 vs quartile 1 hazard ratio 4.0, 95% confidence interval 1.9 to 8.4). In conclusion, in this cohort of patients with advanced HF, there was an independent, dose-dependent association between loop diuretic use and impaired survival. Higher loop diuretic dosages identify patients with HF at particularly high risk for mortality.

Adolescent↗