Use Of Potassium-sparing Diuretics Research Articles

Liver Disease Is a Risk Factor for Recurrent Hyperkalemia: A Retrospective Cohort Study.

Liver disease is often associated with dysfunctional potassium homeostasis but is not a well-established risk factor for hyperkalemia. This retrospective cohort study examined the potential relationship between liver disease and recurrent hyperkalemia. Patients with ≥1 serum potassium measurement between January 2004 and December 2018 who experienced hyperkalemia (serum potassium >5.0 mmol/L) were identified from the United States Veterans Affairs database. A competing risk regression model was used to analyze the relationship between patient characteristics and recurrent hyperkalemia. Of 1,493,539 patients with incident hyperkalemia, 71,790 (4.8%) had liver disease (one inpatient or two outpatient records) within 1 year before the index hyperkalemia event. Recurrent hyperkalemia within 1 year after the index event occurred in 234,807 patients (15.7%) overall, 19,518 (27.2%) with liver disease, and 215,289 (15.1%) without liver disease. The risk of recurrent hyperkalemia was significantly increased in patients with liver disease versus those without (subhazard ratio, 1.34; 95% confidence interval, 1.32-1.37; p < 0.0001). Aside from vasodilator therapy, the risk of recurrent hyperkalemia was not increased with concomitant medication. In this cohort study, liver disease was an independent risk factor strongly associated with recurrent hyperkalemia within 1 year, independent of concomitant renin-angiotensin-aldosterone system inhibitor or potassium-sparing diuretic use.

Risk factors and mortality in elderly patients with severe hyponatremia admitted to the emergency department.

This study was aimed at determining the risk factors associated with mortality in elderly patients with severe hyponatremia admitted to the emergency department. The data of patients aged ≥ 65 years who were admitted to the emergency department and whose serum sodium levels were < 125 mEq/L were retrospectively collected. Mortality was associated with chronic liver disease/cirrhosis (p = 0.036), metastatic tumor (p = 0.007) and solid tumor (p = 0.013) cancers, antiarrhythmic drug use (p = 0.003), potassium-sparing diuretic use (p = 0.044), antineoplastic drug use (p = 0.0029), and dialysis treatment (p = 0.015). The following cutoff values were determined to be predictive of mortality: urea > 63.6 (AUC: 0.771; p = 0.0001), creatinine > 1.39 (AUC: 0.675; p = 0.0003), potassium > 4.64 (AUC: 0.711; p = 0.0001), C-reactive protein > 44 (AUC: 0.765; p = 0.0001), white blood cell count > 12.21 (AUC: 0.688; p = 0.0001), hemoglobin < 11.2 (AUC: 0.611; p = 0.0103), and Charlson comorbidity index > 2 (AUC: 0.739; p = 0.0001). The use of antineoplastic drugs (OR: 4.502; p = 0.010) and increased values of the following were associated with an increased risk of mortality: urea (OR: 1.007; p = 0.024), C-reactive protein (OR: 1.005; p = 0.026), glucose (OR: 1.008; p = 0.001), and Charlson comorbidity index (OR: 1.198; p = 0.025). Malignancy; liver cirrhosis; dialysis treatment; increased Charlson comorbidity index, urea, and C-reactive protein values and the use of antineoplastic drugs are associated with mortality.

Abstract 15924: Identification of Gender- and Age-specific Top Predictors of Hospitalization Due to Heart Failure Using Machine Learning in TOPCAT

Background: NHLBI supported Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) (NCT00094302) investigated whether treatment with spironolactone reduces hospitalization due to heart failure (hHF) in 3,445 adults with prior heart failure and a left ventricular ejection fraction over 45%. We reused publicly available individual patient-level data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) on the American TOPCAT cohort (n=1767) to identify gender and age groups specific baseline (bl) predictors of hHF. Methods: The subjects were stratified into subgroups based on gender (male and female) and age (50-59, 60-69, 70-79, 80-90). Random Survival Forest (RSF), a non-parametric ML approach, evaluated 172 bl variables as predictors of hHF. Top 10 predictors were subsequently included in a multivariate Cox proportional hazards model. Results: The top 10 predictors of hHF are shown in Figure 1. Overall, renal and hematological biomarkers appeared prominently in the top 10 predictors for these patients. While liver markers were among top predictors for hHF in males, diabetes treatment and diabetic complications were top predictors for females. Also, diabetic treatment was a top predictor among age group 50-59, diabetic complications were top predictors among age groups 50-59 and 70-79, liver markers were top predictors among age groups 70-79, and race and years of smoking were top predictors among age group 60-69. Importantly, the use of potassium sparing diuretic at bl was the top predictor among age group 80-90. Conclusion: Using ML, we uncovered in an unbiased fashion, otherwise overlooked bl predictors of hHF in a large, international, multi-center trial like TOPCAT. Thus, ML can help to identify similarities and differences of disease and treatment outcomes among gender, race, ethnicity, and age specific subgroups and advance precision medicine.

Dysnatremias in emergency patients with acute kidney injury: A cross-sectional analysis.

We aimed to investigate the prevalence, risk factors and outcome of hypo- and hypernatremia in emergency patients with acute kidney injury (AKI). In this cross-sectional analysis all emergency patients between January 1st 2017 and December 31st 2018 with measurements of creatinine and sodium were included. Baseline characteristics, medication and laboratory data were gathered. Chart reviews were performed to identify patients with a diagnosis of chronic kidney disease (CKD) and to extract baseline creatinine. For all other patients the ADQI backformula was used to calculate baseline creatinine. AKI was graduated using creatinine criteria of the acute kidney injury network. Binary logistic regression analysis was used to identify risk factors for appearance of dysnatremias and outcome. AKI was found in 8% of patients. 392 patients (23.16%) had hyponatremia, 24 (1.4%) had hypernatremia. Use of potassium sparing diuretics, a medical cause for emergency referral, use of thiazide diuretics and AKI stage were the strongest risk factors for hyponatremia. Loop diuretics, a medical cause for emergency referral and AKI stage were risk factors for hypernatremia. In patients with all classes of hyponatremia, length of hospital stay was significantly longer compared to patients with a normal serum sodium. In the binary logistic regression analysis with death as outcome, hyponatremia as well as severe hypernatremia were independent risk factors for mortality. Dysnatremias are common in emergency patients with AKI. Diuretic medication is a major risk factor for hypo- and hypernatremia. Both hyponatremia and severe hypernatremia were independent risk factors for adverse outcome.

Role of serum magnesium in atrial fibrillation: A study from North Eastern India

Background: Low levels of serum magnesium have been associated in development of post operative atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting. However, the role of magnesium in the development of AF in ambulatory patients is limited. Aim: To evaluate the relation between serum magnesium levels and presence of atrial fibrillation either paroxysmal or permanent. Material and Methods: Hospital-based prospective observational study, between May 2015 and November 2016 in 100 patients (50 cases and controls each) aged ≥ 18years . Admitted patients who had detectable AF on electrocardiography constituted the cases. Patients with any other irregular rhythm , valvular heart disease , history of electrolyte disorder, alcoholism and potassium sparing diuretic use were excluded. Chi-square test, Fisher’s exact test and Pearson’s correlation analysis was used to examine the possible relations between serum magnesium level and other parameters . A p value of <0.05 was considered for statistical significance. Results: The mean age 65.39 ± 11.4 years and 67.18 ±10.6 in the AF and control group respectively. In the AF group 36% had paroxysmal AF and 64% had permanent AF. The serum magnesium levels were significantly lower in the patients with atrial fibrillation (p <0.01) than in controls. The mean serum magnesium levels in paroxysmal AF were 1.49 ± 0.29 while the mean magnesium levels in permanent AF: 1.66 ± 0.36. (p=0.07). Conclusion: Serum magnesium levels were significantly lower in the patients with atrial fibrillation. Correction of magnesium deficiency may be a potential target for the prevention of development of atrial fibrillation.

Risk factors for hyperkalaemia in a cohort of patients with newly diagnosed heart failure: a nested case-control study in UK general practice.

The aim of this study was to identify risk factors for hyperkalaemia in a cohort of patients with newly diagnosed heart failure in the UK. A nested case-control study was conducted using data from The Health Improvement Network primary care database. A cohort of 19 194 patients aged 1-89 years between January 2000 and December 2005 with newly diagnosed heart failure was followed up and cases of hyperkalaemia identified. Cases were frequency matched to controls by age, sex, and calendar year, and information on demographics, co-morbidities, co-medications, and lifestyle factors was extracted from the database. Using unconditional logistic regression models, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to identify potential risk factors. In total, 2176 hyperkalaemia cases were identified over a mean follow-up of 3.9 years. Significant risk factors for hyperkalaemia were: renal failure (OR 3.81; 95% CI 3.29-4.42), type II diabetes (OR 1.52; 95% CI 1.31-1.75), valvular heart disease (OR 1.28; 95% CI 1.06-1.54), and current use of potassium-sparing diuretics (OR 3.01; 95% CI 2.61-3.48), ACE inhibitors (OR 1.70; 95% CI 1.41-2.04), trimethoprim (OR 2.82; 95% CI 1.88-4.23), non-steroidal anti-inflammatory drugs (OR 1.41; 95% CI 1.11-1.79), and several drug combinations. The risk was highest within the first month of medication use and decreased thereafter. Our findings may help to better identify patients with heart failure most likely to benefit from careful monitoring of serum potassium levels. Particular vigilance is needed during the start of treatment with certain medications.

Diagnóstico casual de un síndrome de Gitelman

Gitelman's syndrome is a renal tubule disease of recessive autosomal inheritance in which the fundamental alteration is found in the distal tubule, specifically at the level of the Na/Cl cotransporter, is sensitive to thiazides, and coded in chromosome 16q. It is characterised by a metabolic alkalosis with normal blood pressure, hypokalaemia, as well as hypomagnesaemia and hypocalciuria, which separate it from Bartter's syndrome. Its diagnosis can be delayed up to the adult age, as patients may remain asymptomatic for long periods of time. The treatment consists of oral supplements of potassium and magnesium, and the use of potassium-sparing diuretics and indomethacin has also been described.

Diuretic use is associated with better learning and memory in older adults in the Ginkgo Evaluation of Memory study

To investigate the association between diuretics, angiotensin-converting enzyme inhibitors (ACE-I), angiotensin II receptor blockers (AT2RB), and cognitive function. This post hoc analysis of the randomized controlled Ginkgo Evaluation of Memory Study trial focuses on 3069 nondemented community-dwelling participants aged >75 years. At baseline visit, detailed information about medication use was collected and five cognitive domains were assessed. Multivariate linear regression analyses were used to assess cross-sectional associations between medication use and cognitive function. In all, 36% of participants reported history of hypertension and 53% reported antihypertensive medication use, with 17% reporting diuretic, 11% ACE-I, and 2% AT2RB use. Potassium-sparing diuretic use (N = 192) was associated with better verbal learning and memory measured by California Verbal Learning Test as compared with no antihypertensive medication users (β = 0.068, P = .01; β = 0.094, P < .001) and other antihypertensive medication users (β = 0.080, P = .03; β = 0.153, P < .001). Use of ACE-I or AT2RB was not associated with better cognitive function. Results warrant further investigation into possible protective effects of potassium-sparing diuretics and the role of potassium in mitigating cognitive decline.

PS1-05: Predicting the Risk of Hyperkalemia in Patients with Kidney Disease Starting Angiotensin-Converting Enzyme Inhibitors

Background and Aims: Angiotensin converting enzyme (ACE) inhibitors are widely used in patients with chronic kidney disease (CKD) because the drugs slow disease progression. But some physicians are reluctant to prescribe ACE inhibitors “or use higher doses” because of concerns about the risk of hyperkalemia (high potassium), a potentially fatal adverse effect. Physicians need a tool to help them predict the risk of hyperkalemia; for example, high risk patients could be targeted for intensive laboratory monitoring. We synthesized known predictors of hyperkalemia into a prognostic risk score to predict the risk of hyperkalemia. Methods: We assembled a retrospective cohort of adult patients with possible CKD (at least one recently estimated glomerular filtration rate (eGFR) value less than 60 mL/min/1.73m2) who started an ACE inhibitor between 1998 and 2006 at Kaiser Permanente Northwest, a health maintenance organization (HMO). We followed patients for the earliest evidence of hyperkalemia: potassium value > 5.5 mmol/L; diagnosis code for hyperkalemia (ICD-9-CM 276.7). Cox regression synthesized known predictors of hyperkalemia that were recorded in the electronic medical record or KPNW databases into a risk score to predict the absolute risk of hyperkalemia 90 days after starting therapy. Results: We followed 5,097 patients who experienced 145 hyperkalemic events, a 90-day risk of 2.1% (95% CI 1.9% to 2.4%). The following baseline characteristics predicted hyperkalemia and contributed to the risk score: age, eGFR, diabetes, heart failure, current use of potassium supplements, current use of potassium sparing diuretics (e.g., spironolactone), and a high starting dose for the ACEinhibitor. The risk score discriminated high-risk patients (top quintile, observed risk of 7%) from low risk patients (bottom quintile, observed risk of 0.7%). Predicted and observed risks agreed closely (within 1%) for each quintile. Conclusions: The risk score separated high-risk patients (who may need more intensive laboratory monitoring) from low risk patients (whose physicians could use ACE-inhibitors more confidently). If validated in other clinical settings, the risk score could improve the efficiency of laboratory monitoring for hyperkalemia by focusing attention on higher risk patients.

Hyperkalemia Associated With Inhibitors of the Renin-Angiotensin-Aldosterone System

Maintenance of normal potassium homeostasis is increasingly an important limiting factor in the therapy of cardiovascular disease. Many pharmacological agents that reduce morbidity and mortality in patients with complicated myocardial infarction and chronic heart failure, including β-blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers (ARBs), and aldosterone receptor antagonists, are also known to raise serum potassium and augment the risk of life-threatening hyperkalemia. Conversely, loop diuretics, a mainstay of heart failure treatment, tend to enhance the risk of hypokalemia and ventricular arrhythmias, which may in part account for their consistent dose-related association with increased mortality in observational studies. Because combination drug therapy may simultaneously improve clinical outcomes and enhance the risk of potassium-related adverse events, an appropriate balance of benefit and risk depends heavily on careful patient selection and adequate surveillance of serum potassium and renal function. Article p 1643 The ability of the kidney to maintain potassium homeostasis even as the glomerular filtration rate declines depends critically on adequate sodium delivery to the distal nephron, normal production of aldosterone, and adequate sodium/potassium exchange in the cortical collecting duct.1 Reduction in the filtered sodium load (as a consequence of decreased renal perfusion or reduced cardiac output), diminished aldosterone production, or impaired potassium secretion by the cortical collecting duct (related, for example, to tubulointerstitial disease or use of potassium-sparing diuretics) may attenuate tubular compensatory mechanisms and precipitate hyperkalemia in the vulnerable patient. Aldosterone production is decreased in the elderly, in diabetic patients, and in those receiving drugs that block the production or action of renin (eg, β-blockers, nonsteroidal antiinflammatory drugs, and plasma renin inhibitors) and angiotensin II (angiotensin-converting enzyme inhibitors and ARBs); as a result, these groups, as well as those with already impaired potassium excretion due to progressive age or disease-related decline in glomerular filtration rate, are particularly vulnerable to the …

A Randomized Trial of Electronic Clinical Reminders to Improve Medication Laboratory Monitoring

ObjectiveRecommendations for routine laboratory monitoring to reduce the risk of adverse medication events are not consistently followed. We evaluated the impact of electronic reminders delivered to primary care physicians on rates of appropriate routine medication laboratory monitoring. DesignWe enrolled 303 primary care physicians caring for 1,922 patients across 20 ambulatory clinics that had at least one overdue routine laboratory test for a given medication between January and June 2004. Clinics were randomized so that physicians received either usual care or electronic reminders at the time of office visits focused on potassium, creatinine, liver function, thyroid function, and therapeutic drug levels. MeasurementsPrimary outcomes were the receipt of recommended laboratory monitoring within 14 days following an outpatient clinic visit. The effect of the intervention was assessed for each reminder after adjusting for clustering within clinics, as well as patient and provider characteristics. ResultsMedication-laboratory monitoring non-compliance ranged from 1.6% (potassium monitoring with potassium-supplement use) to 6.3% (liver function monitoring with HMG CoA Reductase Inhibitor use). Rates of appropriate laboratory monitoring following an outpatient visit ranged from 14% (therapeutic drug levels) to 64% (potassium monitoring with potassium-sparing diuretic use). Reminders for appropriate laboratory monitoring had no impact on rates of receiving appropriate testing for creatinine, potassium, liver function, renal function, or therapeutic drug level monitoring. ConclusionWe identified high rates of appropriate laboratory monitoring, and electronic reminders did not significantly improve these monitoring rates. Future studies should focus on settings with lower baseline adherence rates and alternate drug-laboratory combinations.

Exposure to Potentially Inappropriate Drugs and Drug-Drug Interactions in Elderly Nursing Home Residents in Helsinki, Finland

Multiple drug use is common among old, frail nursing home residents who are, as a consequence, susceptible to adverse effects and drug interactions. This study uses the updated Beers criteria for potentially inappropriate drug (PID) use in older adults to determine the extent and nature of PIDs in older nursing home residents in Helsinki, Finland. The study also uses the Swedish, Finnish, INteraction X-referencing (SFINX) interaction database to assess the possibility of clinically significant class D ("clinically significant interaction, and the combination should be avoided") drug-drug interactions (DDIs) in the same population. This study is a cross-sectional assessment of all nursing home residents aged > or = 65 years in Helsinki. The residents' demographic information and medical data were collected from medical charts in February 2003. Of all nursing home residents in Helsinki, 82% (n = 1987) were eligible for analysis. Their mean age was 83.7 (SD 7.7) years, 80.7% were female and 69.5% were diagnosed with dementia. The mean number of drugs given on a regular basis per resident was 7.9 (SD 3.6) per day. Of the study population, 34.9% regularly used at least one PID. Residents taking PIDs were more likely to be taking psychotropic medication and to be taking nine or more drugs daily, and less likely to have a diagnosis of dementia, than patients not taking PIDs. The three most prevalent PIDs were: (i) short-acting benzodiazepines in greater than recommended doses (13.9% of all residents), of which temazepam >15 mg/day was the most commonly used agent and, indeed, the most common PID (taken by 13.5% of all residents); (ii) hydroxyzine (7.1%); and (iii) nitrofurantoin (6.3%). Together, these three PIDs accounted for 76.9% of all PID use. Of all residents, 4.8% were susceptible to a clinically significant DDI. The most common potential DDIs were related to the use of potassium-sparing diuretics, carbamazepine and codeine. Compared with residents not exposed to potential DDIs, residents exposed to potential DDIs were more likely to be younger, to have a prior history of stroke, to be taking psychotropics, to be taking nine or more drugs daily and to be taking PIDs. Use of PIDs is very common among nursing home residents, and this increases the likelihood of DDIs. Monitoring patients for PID use and potential drug interactions could increase the quality of prescribing.

Risk Factors Associated with a High Velocity of the Development of Hyperkalaemia in Hospitalised Patients

Drugs have been recognised as a primary or contributing cause of hyperkalaemia, especially when administered to patients with underlying risk factors. The objective of this study was to analyse the influence of the known risk factors for hyperkalaemia on the velocity of the development of hyperkalaemia. Clinical characteristics, laboratory data and medication profiles of patients developing hyperkalaemia (serum potassium>or=5.0 mmol/L) hospitalised between 2000 and 2004 in the University Hospital Basel, Switzerland, were recorded. Factors associated with a high velocity of the development of hyperkalaemia were detected using a multiple logistic regression model. Subsequently, the velocity during a defined observation period was compared between patients with one risk factor and patients with two or more risk factors. Finally, the dose effects of drugs identified as risk factors for a high velocity of the development of hyperkalaemia were analysed using two sample comparisons. A random sample of 551 hospitalised patients was analysed. Compared with the drug treatment at entry, significantly more patients during the hospitalisation were treated with drugs associated with hyperkalaemia, such as heparins (p<0.001), ACE inhibitors or angiotensin receptor blockers (ARBs) [p=0.002], potassium supplements (p<0.001), potassium-sparing diuretics (p<0.001) and/or NSAIDs or selective cyclo-oxygenase (COX)-2 inhibitors (p<0.001). Risk factors associated with a high velocity of the development of hyperkalaemia were use of potassium supplements (adjusted odds ratio [OR] 3.386; 95% CI 2.251, 5.091), severe renal impairment (OR 3.119; 95% CI 2.007, 4.850), use of ACE inhibitors or ARBs (OR 2.642; 95% CI 1.742, 4.006), use of potassium-sparing diuretics (OR 2.065; 95% CI 1.310, 3.254), and diabetes mellitus (OR 1.525; 95% CI 1.005, 2.313). The velocity of the development of hyperkalaemia significantly increased in patients with two or more risk factors. Dose effects could be found for potassium supplements (p=0.006) and potassium-sparing diuretics (p=0.007), but not for ACE inhibitors or ARBs (p=0.289). In contrast, the use of kaliuretics (loop diuretics or thiazides) was associated with a decreased velocity of the development of hyperkalaemia in patients with serious renal impairment (p=0.016) and in patients treated with two or more drug classes associated with a high velocity of the development of hyperkalaemia (p=0.001). Risk factors associated with a high velocity of the development of hyperkalaemia are use of potassium supplements>severe renal impairment>use of ACE inhibitors or ARBs>use of potassium-sparing diuretics>diabetes mellitus. The presence of two or more of these risk factors is associated with an even faster development of hyperkalaemia. Clinicians should be aware of these risk factors in order to avoid a rapid development of potentially life-threatening hyperkalaemia.

Aldosterone excretion is related to severity of sleep apnea in men and not in women with resistant hypertension

We have previously reported that aldosteronism is related to body mass in men but not in women with resistant hypertension. The purpose of this study is to determine if severity of sleep apnea may contribute to this gender difference in patients with resistant hypertension. Consecutive subjects referred to the University of Alabama at Birmingham (UAB) Hypertension clinic for resistant hypertension were prospectively evaluated with an early morning plasma renin activity (PRA) and plasma aldosterone concentration (PAC). A 24-hour urine collection for aldosterone, sodium and creatinine was also obtained during an ad-lib diet. All subjects were on a stable antihypertensive regimen without use of potassium-sparing diuretics. All subjects were evaluated by full-night polysomnography at the UAB Sleep-Wake Disorders Center for the number of apnea-hypopnea events/hour, or the respiratory disturbance index (RDI). Biochemical assessment and polysomnography was performed on a total of 43 subjects (30 males and 13 females) with resistant hypertension. The RDI was positively and significantly correlated with urinary aldosterone levels (r=0.46, p=0.015) and PAC/PRA ratio (r=0.53, p=0.003) in male subjects. In contrast, RDI was not related to aldosterone excretion or the PAC/PRA ratio in female subjects. These results suggest that excess aldosterone excretion may be secondary to untreated sleep apnea in men with resistant hypertension. Open in new tabDownload slide

Hyperkalemia in Chronic Kidney Disease

Potassium balance and serum potassium level are maintained until very late in chronic kidney disease (CKD), mainly because of an increase in renal and colonic excretion. Hyperkalemia may develop earlier in the course of CKD in patients with hyporeninemic hypoaldosteronism. Hyperkalemia in CKD patients may occur in association with excess dietary potassium intake, constipation or prolonged fasting. It may also be seen with the use of potassium-sparing diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and non-steroidal anti-inflammatory drugs. If suspected, pseudohyperkalemia should be excluded to avoid unnessary treatments. Acute treament of hyperkalemia in marked or symptomatic hyperkalemia, particularly in the presence of electrocardiographic changes includes combinations of intravenous calcium gluconate and infusions of glucose and insulin with or without bicarbonate. In patients with kidney failure, dialysis may be required. Either asymptomatic and mild hyperkalemia or chronic hyperkalemia in CKD patients can be treated by potassium restriction, a loop diuretic at high doses, and cation exchange resin.

Diuretic use, progressive heart failure, and death in patients in the studies of left ventricular dysfunction (SOLVD)

ObjectivesWe sought to determine whether non–potassium-sparing diuretics (PSDs) in the absence of a PSD may result in progressive heart failure (HF). BackgroundAngiotensin-converting enzyme (ACE) inhibitors incompletely suppress ACE activity in HF patients. Furthermore, non-PSDs are activators of aldosterone secretion. We reasoned that non-PSDs, in the absence of a PSD, might result in progressive HF. MethodsIn the 6,797 patients in the Studies Of Left Ventricular Dysfunction (SOLVD), we compared the risk of hospitalization for, or death from, HF between those taking a PSD and those who were not, adjusting for known covariates. ResultsThe risk of hospitalization from worsening HF in those taking a PSD relative to those taking only a non-PSD was 0.74 (95% confidence interval [CI] 0.55 to 0.99; p = 0.047). The relative risk for cardiovascular death was 0.74 (95% CI 0.59 to 0.93; p = 0.011), for death from all causes 0.73 (95% CI 0.59 to 0.90; p = 0.004), and for hospitalization for, or death from, HF 0.75 (95% CI 0.58 to 0.97; p = 0.030). Compared with patients not taking any diuretic, the risk of hospitalization or death due to worsening HF in patients taking non-PSDs alone was significantly increased (risk ratio [RR] = 1.31, 95% CI 1.09 to 1.57; p = 0.0004); this was not observed in patients taking PSDs with or without a non-PSD (RR = 0.99, 95% CI 0.76 to 1.30; p = 0.95). ConclusionsThe use of PSDs in HF patients is associated with a reduced risk of death from, or hospitalization for, progressive HF or all-cause or cardiovascular death, compared with patients taking only a non-PSD.

Diabetes insipidus.

Diabetes insipidus.

Diuretics and risk of arrhythmic death in patients with left ventricular dysfunction.

Background-Treatment with diuretics has been reported to increase the risk of arrhythmic death in patients with hypertension. The effect of diuretic therapy on arrhythmic death in patients with left ventricular dysfunction is unknown. Methods and Results-We conducted a retrospective analysis of 6797 patients with an ejection fraction <0.36 enrolled in the Studies Of Left Ventricular Dysfunction (SOLVD) to assess the relation between diuretic use at baseline and the subsequent risk of arrhythmic death. Participants receiving a diuretic at baseline were more likely to have an arrhythmic death than those not receiving a diuretic (3.1 vs 1.7 arrhythmic deaths per 100 person-years, P=0.001). On univariate analysis, diuretic use was associated with an increased risk of arrhythmic death (relative risk [RR] 1.85, P=0.0001). After controlling for important covariates, diuretic use remained significantly associated with an increased risk of arrhythmic death (RR 1.37, P=0.009). Only non-potassium-sparing diuretic use was independently associated with arrhythmic death (RR 1.33, P=0.02). Use of a potassium-sparing diuretic, alone or in combination with a non-potassium-sparing diuretic, was not independently associated with an increased risk of arrhythmic death (RR 0.90, P=0.6). Conclusions-In SOLVD, baseline use of a non-potassium-sparing diuretic was associated with an increased risk of arrhythmic death, whereas baseline use of a potassium-sparing diuretic was not. These data suggest that diuretic-induced electrolyte disturbances may result in fatal arrhythmias in patients with systolic left ventricular dysfunction.

Drug Use and Low Blood Pressure in the Elderly

The aim of the present study was to examine the prevalence of low blood pressure in an older population with respect to medication with drugs with potential hypotensive effects. Data from the Kungsholmen Project was used, a population-based study of elderly people aged 75 years and over in Stockholm, Sweden. Among the 1810 participants, 1748 with documentation on blood pressure and drug use were included in the study. Low systolic blood pressure, defined as <125mm Hg, was found in 157 subjects. Low diastolic blood pressure, defined as <65mm Hg, was found in 124 subjects. The association between drug use and low blood pressure was examined for drugs with known potential hypotensive effects (sympatholytic drugs, diuretics, beta-receptor blocking drugs, calcium antagonists, angiotensin-converting enzyme inhibiting drugs, nitrates, antiparkinsonian drugs, neuroleptics, anxiolytics, sedatives-hypnotics and antidepressant drugs) in a logistic regression model controlling for the possible confounders age, gender, housing, dementia status, cardiovascular disease, body mass index and dehydration. The use of potassium-sparing diuretics, dopaminergic antiparkinsonian drugs and neuroleptics showed a significant association with low systolic blood pressure. Dopaminergic antiparkinsonian drugs were significantly associated with low diastolic blood pressure. This may imply a risk in the elderly, where some of these drugs are commonly used, considering results from previous studies suggesting that low blood pressure may cause, for example, falls and fractures, accelerated dementia, myocardial ischaemia, cerebral ischaemia, and increased mortality in this age group.

Potassium supplements and potassium-sparing diuretics. A review and guide to appropriate use.

Epidemiological and clinical studies suggest that low dietary potassium intake may have an important role in determining the development of diseases such as hypertension, and perhaps even stomach cancer, and that increased potassium intake may have beneficial effects in several other conditions. Dietary adjustment or active potassium supplementation has been suggested as a natural, less costly and safe method of increasing potassium levels, although active supplementation with tablets or solutions is not recommended in healthy people with normal serum potassium levels. However, increasing dietary potassium intake in the elderly and in patients with renal impairment must be considered with caution. Diuretics have a long established role in the management of hypertension and heart failure. There is no convincing evidence to suggest that the small reduction in plasma potassium levels associated with low dose thiazide and loop diuretic therapy needs to be routinely prevented by the use of potassium-sparing drugs. In non-digitalised patients little association has been found between mild diuretic-induced hypokalaemia and arrhythmias. Thus, the routine prophylactic use of potassium-sparing diuretics in combination with non-potassium-retaining diuretics for the treatment of hypertension and oedematous states is not justified. Based on current evidence, treating all patients whose serum potassium level decreases below 3 mmol/L is recommended, although for certain patients at particular risk of hypokalaemia, levels may need to be maintained above 3.5 mmol/L. In overt hypokalaemia, several therapeutic options are available to the clinician. These include increased consumption of potassium-rich foods, the use of salt substitutes, medicinal potassium supplementation or distal tubular (potassium-sparing) diuretics.