Diuretic Group Research Articles

The effect of tolvaptan on renal excretion of electrolytes and urea nitrogen in patients undergoing coronary artery bypass surgery.

BackgroundAdequate fluid management is an important component of patient care following cardiac surgery. Our aim in this study was to determine the benefits of tolvaptan, an oral selective vasopressin-2 receptor antagonist that causes electrolyte-free water diuresis, in postoperative fluid management. We prospectively examined the effect of tolvaptan on renal excretion of electrolytes and urea nitrogen in cardiac surgery patients.MethodsPatients undergoing coronary artery bypass surgery were randomized to receive conventional loop diuretics (Group C, n = 30) or conventional loop diuretic therapy plus tolvaptan (Group T, n = 27). Fractional excretions of sodium (FENA), potassium (FEK) and urea nitrogen (FEUN) were measured in both groups during post-surgical hospitalization.ResultsUrine output was greater with tolvaptan (Group T) than without it (Group C), and some patients in Group C required intravenous as well as oral loop diuretics. Serum sodium concentrations decreased after surgery in Group C, but were unchanged in Group T (postoperative day [POD] 3, 139.8 ± 3.5 vs. 142.3 ± 2.6 mEq/L, p = 0.006). However, postoperative FENA values in Group C did not decrease, and the values were similar in both groups. Serum potassium levels remained lower and FEK values remained higher than the preoperative values, but only in Group C (all p < 0.05). BUN increased postoperatively in both groups, but it remained higher than its preoperative value only in Group C (all p < 0.01). Group T showed an initial increase in BUN, which peaked and then returned to its preoperative value within a week. The FEUN increased postoperatively in both groups, but the change was more pronounced in Group T (POD7, 52.7 ± 9.3 vs. 58.2 ± 6.5 %, p = 0.025).ConclusionsRenal excretion of sodium and potassium reflects the changes in serum concentration in patients treated with tolvaptan. Patients treated only with loop diuretics showed a continuous excretion of sodium and potassium that led to electrolyte imbalance, whereas the combination of loop diuretics and tolvaptan increased renal urea nitrogen elimination. Tolvaptan therefore appears to be an effective diuretic that minimally affects serum electrolytes while adequately promoting the elimination of urea nitrogen from the kidneys in patients undergoing coronary artery bypass surgery.Trial registrationThe present study is registered with the UMIN Clinical Trials Registry (ID: UMIN000011039)

MPS 10-08 Renoprotective effect of eplerenone in comparison to thiazide diuretic in hypertensive patients with chronic kidney disease

Objective: The aim of the present study was to compare the anti-albuminuric effect of addition of eplerenone and thiazide diuretic to hypertensive patients with chronic kidney disease treated with angiotensin II receptor blocker (ARB). This study is sub-analysis of OWASE (Optimal hypertension therapy With Aldosterone blocker SElara) study that we presented in the 37th annual scientific meeting of the Japanese Society of Hypertension. Design and Method: The present study was a multicenter, prospective, open-label randomized, controlled study. We enrolled hypertensive patients, who had received an ARB, with albuminuria (pre-treatment urinary albumin/creatinine [Cr] ratio [UACR] 30–300 mg/gCr), and an estimated glomerular filtration rate (eGFR) ≥36 ml/min/1.73 m2. Eligible patients were randomly assigned to either receive eplerenone (50 mg daily) or thiazide diuretic (hydrochlorothiazide 12.5 mg daily or trichlormethiazide 1 mg daily) with standard antihypertensive therapy for 48 weeks. The primary end point was the mean percent change in the UACR from baseline to 48 weeks. Results: Of the assigned patients, 68 (42 in the eplerenone group and 26 in the thiazide diuretic group) were included in the efficacy analysis. Baseline UACR was similar in the two groups (eplerenone, 121.7 mg/gCr; thiazide diuretic, 99.4 mg/gCr, P = 0.230). Baseline systolic blood pressure was significantly higher in the thiazide diuretic group than the eplerenone group (eplerenone, 143.7 mmHg; thiazide diuretic, 155.4 mmHg, P = 0.001), however, achieved systolic blood pressure was similar in the two groups at 48 weeks (eplerenone, 135.5 mmHg; thiazide diuretic, 137.6 mmHg, P = 0.609). In the primary efficacy analysis, the mean percent change in the UACR from baseline to 48 weeks was similar in the two groups (eplerenone, −31.9%; thiazide diuretic, −37.6%, P = 0.735). Conclusions: The renoprotective effect of eplerenone combined therapy was similar to thiazide diuretic when combined with ARB in hypertensive patients with CKD.

Vascular stiffness in patients with arterial hypertension: possible antihypertensive therapy

The article discusses the factors that increase the arterial stiffness: the blood pressure, atherosclerosis, smoking, diabetes, age. Given evidence that pulse wave velocity and a number of other indicators that reflect the state of the vascular wall, are markers for increased risk of cardiovascular complications and mortality. The influence of antihypertensive drugs of different groups on the stiffness of the vascular wall, with particular attention paid to the effects of drugs from group of diuretics. We discuss possible mechanisms of the influence of indapamide retard on the elastic properties of vessels. It is emphasized that the influence on the stiffness of the arteries of different antigipertenzivny medicines, even belong to the same class, is different, due to differences in pharmacokinetic properties.

The Short- and Long-Term Outcome of Intratympanic Steroid Therapy as a Salvage Treatment for Acute Low-Tone Sensorineural Hearing Loss without Episodes of Vertigo

Objectives: To evaluate the hearing outcomes of intratympanic steroid (ITS) treatment for patients with acute low-tone sensorineural hearing loss (ALHL) after failure of initial therapy and to investigate the recurrence and progression to definite Ménière's disease (MD) during a long-term follow-up. Methods: We retrospectively reviewed the medical records of 90 patients with refractory ALHL who were followed up for at least 1 year between January 2000 and April 2014. Patients who responded poorly to initial medical treatment received intratympanic dexamethasone injections (ITS group) or isosorbide administration for 4 weeks (diuretic group) as salvage treatment options according to their choice of management. The control group did not receive ITS or the diuretic, due to their refusal of both medical treatments. The hearing outcomes were evaluated 1 month, 1 year and 5 years after the completion of the second-line therapy, and the rates of recurrence and progression to MD were measured during a follow-up period of at least 1 year. Results: Twenty-seven patients in the ITS group, 39 patients in the diuretic group and 24 patients in the control group were enrolled. Of these, 12 patients in the ITS group, 15 patients in the diuretic group and 12 patients in the control group were followed up for over 5 years. We found that the recovery rates and the audiometric functional values after 1 month and 1 year in the ITS group were significantly higher than those in the diuretic and control groups. However, there were no significant differences in the recovery rates or the audiometric functional values after 5 years, or in the rates of recurrence and progression to MD between the groups. Conclusions: Salvage ITS therapy can provide a relatively good short-term hearing outcome for ALHL patients who have persistent hearing loss despite conventional treatment. However, both recurrence and progression to MD after treatment were observed in some patients during the long-term follow-up.

Clinical and genetic features of diuretic-associated gout: a case-control study.

Hyperuricaemia and gout are well-recognized complications of diuretic use. The aim of this study was to examine the clinical and genetic features of diuretic-associated gout. Participants (n = 1365) fulfilling the 1977 ARA gout classification criteria, recruited from primary and secondary care, attended a study visit that included a detailed clinical assessment. Use of diuretic therapy was recorded during the study visit, and was confirmed by electronic dispensing data [n = 426 (31.2%) on diuretics]. Gout-associated single nucleotide polymorphisms were genotyped. Clinical and genetic features of diuretic-associated gout were analysed using a case-control study design (diuretics vs no diuretics). In the diuretic group there were more women, higher rates of comorbid conditions, higher BMI and lower estimated glomerular filtration rate compared with those not taking diuretics. Gout disease duration, frequency of gout flares and presence of tophi were similar in the two groups. Patients on diuretics had higher age of gout presentation and higher recorded serum urate. The ABCG2 rs2231142 risk allele was present less frequently in the diuretic group (36.1%) compared with those not on diuretics (47.6%, P = 1.2 × 10(-4)). The differences in ABCG2 were observed in both men and women with gout. Diuretic-associated gout represents a medically complex condition. Although age of gout onset is later and serum urate concentrations are higher in those on diuretics, other clinical features of gout are similar. The observed differences in the ABCG2 risk allele frequency suggest that some genetic factors play a less dominant role in diuretic-associated gout compared with primary gout.

Postural Changes in Measures of Arterial Stiffness in Hypertensive Subjects on Antihypertensive Drug Therapy: A Prospective, Pilot Study.

Prospective study with a controlled arm to know if there are variations of measures of arterial stiffness with posture in subjects with hypertension on antihypertensive medications. We studied postural variations of measures of arterial stiffness in 21 subjects with diagnosed hypertension on antihypertensive medications and compared them with 21 normotensive subjects. All subjects underwent pulse-wave analysis on SphygmoCor in the morning between 8 am to 10 am initially in supine and then in sitting position after 3 minutes. Summary measures on demographics, and blood pressure characteristics at sitting and supine positions are obtained. Differences between characteristics at supine and sitting position are compared using nonparametric paired test of Wilcoxon signed-rank test. A value of p < 0.05 was accepted as statistically significant. Antihypertensive medications decreased the supine aortic augmentation pressure (AAP) and augmentation index (AI) but not significantly. When subgroups of patients with antihypertensive treatment were analyzed, it was noted that angiotensin-converting enzyme inhibitor and angiotensin receptor blocker group (12) decreased AAP and AI significantly in supine position compared with patients on other antihypertensive medications (9) (p-value 0.034 and 0.038, respectively). There was no significant difference in other groups of calcium channel blockers, β-blockers, or diuretics. However, in normotensive control arm, there was an increase in AAP and AI in the supine position. In hypertensive subjects, on antihypertensive, there was reduction in AAP and AI in supine position compared with those of normotensives. The significance of the decrease in AAP and AI in supine position on antihypertensive needs to be studied further.

Сосудистая жесткость у больных артериальной гипертензией: возможности антигипертензивной терапии

The article discusses the factors that increase the arterial stiffness: the blood pressure, atherosclerosis, smoking, diabetes, age. Given evidence that pulse wave velocity and a number of other indicators that reflect the state of the vascular wall, are markers for increased risk of cardiovascular complications and mortality. The influence of antihypertensive drugs of different groups on the stiffness of the vascular wall, with particular attention paid to the effects of drugs from group of diuretics. We discuss possible mechanisms of the influence of indapamide retard on the elastic properties of vessels. It is emphasized that the influence on the stiffness of the arteries of different antigipertenzivny medicines, even belong to the same class, is different, due to differences in pharmacokinetic properties.

The randomized prospective study of non-surgical management of patients with mild to moderate carpel tunnel syndrome

Objective: To evaluate effectiveness of used oral medications such as diuretics, steroids and local steroid injections in the treatment of mild to moderate CTS. Methods: Prospective randomized study of patients with clinical symptoms and signs of CTS, confirmed by standard electrodiagnosis. Baseline assessments included a standardized Boston questionnaire to assess symptom severity score, functional severity score, total score, relevant clinical examination and necessary nerve conduction studies (NCS). After the baseline assessment, patients were randomized to following treatment arms:1. Steroid local injection (n = 64)2. Oral steroid for 28 days (n = 64)3. Oral steroid + diuretics for 28 days (n = 69) Boston questionnaire symptom severity score, functional severity score, total score and the NCS results were analyzed after 28 days of treatment. Results: Boston questionnaire scores (symptom severity score, functional severity score and total score) were significantly improved with all three treatment modalities after 4 weeks of treatment p &lt;0.05 the values of each indicator was more or less similar in each group at the baseline. The percentage of improvement is highest with steroid injection and lowest with oral steroids and steroids + diuretic group falling in between. Sensory nerve conduction studies showed an improvement in all three treatment modalities. But a statistically significant improvement was seen in steroid injection and oral steroid + diuretic groups only p &lt;0.05. Conclusion: All three treatment modalities i.e. steroid injections, oral steroids, and oral steroid and diuretics are effective in treating mild to moderate CTS. The improvement seen with steroid injection is more than that is seen in the other two interventions.

Loop diuretics, renal function and clinical outcome in patients with heart failure and reduced ejection fraction.

We aimed to study the relationships of loop diuretic dose with renal function and clinical outcomes in patients with chronic heart failure (HF). Loop diuretic dose at baseline was recorded in patients included in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). The relationship to change in estimated glomerular filtration rate (eGFR) over time and to the first occurrence of the composite outcome of cardiovascular (CV) death or hospitalization owing to HF was examined in propensity score matched cohorts. Of the 5011 patients, 2550, 745, and 449 were receiving >80 mg (high), 41-80 mg (medium) and ≤40 mg (low) of loop diuretics in furosemide equivalent daily dosages, respectively, which were used to assemble 229, 385, and 1045 pairs of propensity-matched high, medium, and low dose cohorts. Compared with matched no loop diuretic groups, eGFR declined 0.3 ± 0.2, 0.3 ± 0.3 and 1.2 ± 0.5 mL/min/1.73 m(2) /year in the low-, medium-, and high-dose groups, respectively. Compared with matched no loop diuretic groups, hazard ratios (HR) (95% confidence intervals) for outcome associated with low-, medium- and high-dose groups were 1.71 (1.41-2.06), 1.99 (1.50-2.64), and 2.94 (1.95-4.41), respectively. Higher loop diuretic dose was particularly associated with increased risk for hospitalization owing to HF: HR 4.80 (2.75-8.37), P < 0.001. The use of loop diuretics was associated with a slightly greater rate of decline in eGFR, which did not vary significantly by diuretic dose.Loop diuretic dose was associated with higher risks of (CV) mortality and predominantly hospitalization owing to HF, which appeared to be higher among those receiving higher daily doses.

ДОСЛІДЖЕННЯ АСОРТИМЕНТУ АНТИГІПЕРТЕНЗИВНИХ ПРЕПАРАТІВ, ЩО ПРЕДСТАВЛЕНІ НА ФАРМАЦЕВТИЧНИХ РИНКАХ УКРАЇНИ ТА ПОЛЬЩІ

&lt;h2&gt;RESEARCH OF ANTIHYPERTENSIVE MEDICINESʼ ASSORTMENT WHICH ARE PRESENTED IN PHARMACEUTICAL MARKETS OFUKRAINEANDPOLAND&lt;/h2&gt;&lt;h2&gt;N.Yu. Poluychak, M.B. Demchuk, O.О. Yurуeva&lt;sup&gt;1&lt;/sup&gt;, T.A. Groshovyi,&lt;/h2&gt;&lt;h2&gt;SHEI «TernopilStateMedicalUniversityby I.Ya. Horbachevsky»&lt;/h2&gt;&lt;h2&gt;&lt;sup&gt;1&lt;/sup&gt;JSC «Farmak»&lt;/h2&gt;&lt;h2&gt;Summary. The article analyzes the antihypertensive medicinesʼ assortment which is presented in the pharmaceutical markets ofUkraineandPoland. Assortment policies of pharmaceutical manufacturers of antihypertensive drugs, diuretics, b-adrenergic blockers, calcium antagonists, drugs that affect the renin-angiotensin system are analyzed.&lt;/h2&gt;&lt;h2&gt;Key words: hypertension, pharmaceutical market ofUkraine, pharmaceutical market ofPoland, antihypertensive medicines.&lt;/h2&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction. &lt;/strong&gt;Diseases of the cardiovascular system (CAS) are the leader in the structure of morbidity and mortality in the adult population of highly developed countries. Among pathology of CAS the most common is arterial hypertension (AH), which is found in 15-20% of adults in industrialized countries and is recognized as a chronic no communicable disease. Despite the global nature of the prevalence of hypertension, certain regions of the world differ greatly on this indicator. AG has acquired a large spread in the European Region.&lt;/p&gt;&lt;p&gt; All classes of antihypertensive agents recommended by the European Society of Cardiology and the Society for AH (2003), US Joint National Committee (7th revision, 2003) and Ukrainian Society of Cardiology (2004) as first-line drugs in the treatment of hypertension, almost equally reduce blood pressure. It is well known that such pharmacological groups that can be used as part of a monotherapy and in combination therapy include the following drugs: diuretics; angiotensin-converting enzyme (ACE) inhibitors; calcium channel blockers; angiotensin II receptor antagonists; β-blockers. The group of second-line drugs is forming alpha 1-blockers; Rauvolfia alkaloids; central α2-agonists; imidazoline receptor agonist drugs.&lt;/p&gt;&lt;p&gt; The purpose of this study is to&lt;strong&gt; &lt;/strong&gt;study the assortment medicines for the treatment of hypertension, which are available to consumers onUkraine by comparison with an assortment of antihypertensive drugs, which are represented in the pharmaceutical market inPoland.&lt;/p&gt;&lt;p&gt; &lt;strong&gt;Methods.&lt;/strong&gt; Analysis of the assortment of drugs that are presented in the domestic pharmaceutical market conducted under Ukrainian State Register of medicines. For the study of current state of the Polish market of antihypertensive agents, the Polish State Register of medicines and official website http://pharmindex.pl, http://leki-informacje.pl., is applied.&lt;/p&gt;&lt;p&gt; &lt;strong&gt;Results and discussion&lt;/strong&gt;. According to the State Register of medicines ofUkraine by January2015, a group of antihypertensive drugs consists of more than 790 drugs. The antihypertensive agentsʼ group represented more than 940 drugs on the Polish pharmaceutical market. According to ATC - classification analyzed following groups: C02 - antihypertensive drugs, C03 - diuretics, C07 - beta blocking agents, C08 - calcium channel blockers, C09 - agents acting on the renin-angiotensin system.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions. &lt;/strong&gt;The majority of medicines, which are offered on the European markets, are represented in domestic market. The exclusions are the medicines, which contain clopamide, chlortalidone, canreon – from the diuretics group, pindolol and acetebulol – from the β-blockers group, isradipine – from the group of calcium channel blockers, benazepril, cilazapril, trandolapril and imidapril – from angiotensin-converting-enzyme inhibitors group. Assortment of antihypertensive medicines in the market of Poland is represented by combined medicines of benazepril with diuretics, cilazapril with diuretics, ramipril with felodipine, aliskiren with amlodipine, which are absent on the domestic market.&lt;/p&gt;

Rationale and design of the Aquapheresis Versus Intravenous Diuretics and Hospitalization for Heart Failure (AVOID-HF) trial

In patients hospitalized with acutely decompensated heart failure, unresolved signs and symptoms of fluid overload have been consistently associated with poor outcomes. Regardless of dosing and type of administration, intravenous loop diuretics have not reduced heart failure events or mortality in patients with acutely decompensated heart failure. The results of trials comparing intravenous loop diuretics to mechanical fluid removal by isolated venovenous ultrafiltration have yielded conflicting results. Studies evaluating early decongestive strategies have shown that ultrafiltration removed more fluid and was associated with fewer heart failure-related rehospitalization than intravenous loop diuretics. In contrast, when used in the setting of worsening renal function, ultrafiltration was associated with poorer renal outcomes and no reduction in heart failure events. The AVOID-HF trial seeks to determine if an early strategy of ultrafiltration in patients with acutely decompensated heart failure is associated with fewer heart failure events at 90 days compared with a strategy based on intravenous loop diuretics. Study subjects from 40 highly experienced institutions are randomized to either early ultrafiltration or intravenous loop diuretics. In both treatment arms, fluid removal therapies are adjusted according to the patients' hemodynamic condition and renal function. The study was unilaterally terminated by the sponsor in the absence of futility and safety concerns after the enrollment of 221 subjects, or 27% of the originally planned sample size of 810 patients. The AVOID-HF trial's principal aim is to compare the safety and efficacy of ultrafiltration vs that of intravenous loop diuretics in patients hospitalized with acutely decompensated heart failure. Because stepped treatment approaches are applied in both ultrafiltration and intravenous loop diuretics groups and the primary end point is time to first heart failure event within 90 days, it is hoped that the AVOID-HF trial, despite its untimely termination by the sponsor, will provide further insight on how to optimally decongest patients with fluid-overloaded heart failure.

PP.21.30

Objective: To observe the reverse effect of different combined regimens on blood pressure and microalbuminuria(MAU) in hypertensive patients. Design and method: Ninety-four hypertensive patients with blood pressure > 140/90 mmHg (1 mmHg = 0.133 kPa) and positive MAU after treatment with inhibitors of angiotensin invertase and antagonists of angiotensin receptor were included in this study. The patients were randomly divided into L-amlodipine group (n = 52) and diuretics (HCTZ) group (n = 42). After the patients were treated with L-amlodipine(2.5–5 mg/d) and HCTZ(12.5–25 mg/d) respectively for 12 weeks, the reverse effect of different regimens on blood pressure and MAU was observed. Results: The normal blood pressure was achieved in 35(67.3%)and 27 patients(64.3%) respectively(P > 0.05), the negative MAU rate was 53.8% and 19.0% respectively (P < 0.01), the blood pressure was < 140/90 mmHg and the MAU was no less than30% in 80.8% and 64.3% of the patients in the two groups 12 weeks after treatment(P < 0.05). Conclusions: The effect of renin and angiotensin blocking agents in combination with calcium antagonists or HCTZ is similar to that of other regimens on blood pressure and other parameters, and is better than that of renin and angiotensin blocking agents in combination with HCTZ on MAU.

Use of Loop Diuretics is Associated with Increased Mortality in Patients with Suspected Coronary Artery Disease, but without Systolic Heart Failure or Renal Impairment: An Observational Study Using Propensity Score Matching.

BackgroundLoop diuretics are widely used in patients with heart and renal failure, as well as to treat hypertension and peripheral edema. However, there are no randomized, controlled trials (RCT) evaluating their long term safety, and several observational reports have indicated adverse effects. We sought to evaluate the impact of loop diuretics on long term survival in patients with suspected coronary artery disease, but without clinical heart failure, reduced left ventricular ejection fraction or impaired renal function.Method and FindingsFrom 3101 patients undergoing coronary angiography for suspected stable angina pectoris, subjects taking loop diuretics (n=109) were matched with controls (n=198) in an attempted 1:2 ratio, using propensity scores based on 59 baseline variables. During median follow-up of 10.1 years, 37.6% in the loop diuretics group and 23.7% in the control group died (log-rank p-value 0.005). Treatment with loop diuretics was associated with a hazard ratio (95% confidence interval) of 1.82 (1.20, 2.76), and the number needed to harm was 7.2 (4.1, 30.3). Inclusion of all 3101 patients using propensity score weighting and adjustment for numerous covariates provided similar estimates. The main limitation is the potential of confounding from unmeasured patient characteristics.ConclusionsThe use of loop diuretics in patients with suspected coronary artery disease, but without systolic heart failure or renal impairment, is associated with increased risk of all-cause mortality. Considering the lack of randomized controlled trials to evaluate long term safety of loop diuretics, our data suggest caution when prescribing these drugs to patients without a clear indication.

Effect of diuretics and sodium-restricted diet on sleep apnea severity: study protocol for a randomized controlled trial.

BackgroundObstructive sleep apnea occurs as a result of increased collapsibility of the upper airway. Overnight fluid displacement from the legs to the neck causes pharyngeal narrowing and increased apnea severity. Sodium intake is associated with apnea severity. We hypothesized that interventions that decrease bodily fluid content might reduce the severity of sleep apnea.Methods/designThis is a randomized clinical trial including men with an apnea-hypopnea index greater than 30 events/hour, previously diagnosed by full-night in-laboratory polysomnography. A total of 54 men will be included and randomly assigned to three groups: Diuretic (n = 18), sodium-restricted diet (n = 18), and control (n = 18). The intervention will last one week. Intention-to-treat and per-protocol analyses will be performed. The diuretic group will receive combined spironolactone 100 mg plus furosemide 20 mg daily, taken in the morning. The diet group will receive a regimen with a maximum intake of 3 g of sodium per day. The control group will receive a placebo pill and will maintain all eating habits while keeping a recall diary of their dietary behavior. The primary outcome measure will be change in apnea-hypopnea index. The secondary outcome measures will be variations of: anthropometric and bioelectrical impedance variables, office blood pressure, respiratory variables from in-home level III polysomnography, excessive daytime sleepiness, glycolipid profile, C-reactive protein, 24 h urinary variables, and adverse events.DiscussionDespite the high efficacy of continuous positive airway pressure to reverse upper airway obstruction in sleep apnea, partial adherence to this form of treatment reduces its efficiency. Thus, additional forms of treating apnea need to be investigated. If the results of this proof-of-concept trial show that decreases in bodily fluid content, either by diuretic or dietary intervention, reduces the severity of sleep apnea, further investigation will be necessary before these results can be translated and adopted as an adjunct apnea therapy.Trial registrationclinicaltrials.gov NCT01945801.

Diuretics and bioimpedance-measured fluid spaces in hypertensive patients.

The authors examined the relationship between thiazide-type diuretics and fluid spaces in a cohort of hypertensive patients in a retrospective study of 60 stable hypertensive patients without renal abnormalities who underwent whole-body bioimpedance analysis. Overhydration was greater in the diuretic group, but only to a nonsignificant degree (5.9 vs. 2.9%; P=.21). The total body water did not differ in the two groups (41.8 L vs. 40.5 L; P=.64). Extracellular fluid volume (ECV) (19.7 L vs. 18.5 L; P=.35) and intracellular fluid volume (ICV) spaces (20.8 L vs. 21.3 L; P=.75) were also not significantly different in the two groups. The ratio of ICV:ECV, however, appeared different: 1.05 vs 1.15 (P=.017) and the effect was maintained in the linear regression-adjusted model (β coefficient: -0.143; P=.001). The diuretic-related distortion of ICV:ECV ratio indicates potential fluid redistribution in hypertensive patients, with ICV participating in the process.

Comparison of olmesartan combined with a calcium channel blocker or a diuretic in elderly hypertensive patients (COLM Study): safety and tolerability.

The cardiovascular effects of combined therapy with the angiotensin receptor blocker (olmesartan) and a dihydropyridine calcium channel blocker (CCB) or a diuretic were compared in high-risk elderly Japanese hypertensive patients by performing a randomized, open label, blinded-endpoint study of morbidity and mortality (the COLM study). Here we report the results obtained with respect to safety and tolerability. High-risk hypertensive patients aged 65–84 years were enrolled and were randomized to receive olmesartan combined with either a CCB (amlodipine or azelnidipine) or a low-dose diuretic for at least 3 years. The primary endpoint was a composite of fatal and non fatal cardiovascular events, whereas adverse events (AEs) and the percentage of patients who discontinued the allocated treatment were evaluated as secondary endpoints. A total of 5141 patients were randomized. Both combination regimens achieved a similar reduction of cardiovascular morbidity and mortality. The incidences of AEs, serious AEs, drug-related serious AEs and discontinuation due to serious AEs were lower in the olmesartan plus CCB group than in the olmesartan plus diuretic group. Serum levels of uric acid and creatinine were significantly higher in the olmesartan plus diuretic group than in the olmesartan plus CCB group. Olmesartan combined with a CCB was significantly superior to olmesartan plus a diuretic with regard to the frequency of AEs and discontinuation of treatment.

Combination therapy of hypertension in the elderly: a subgroup analysis of the Combination of OLMesartan and a calcium channel blocker or diuretic in Japanese elderly hypertensive patients trial.

Combination of OLMesartan and a calcium channel blocker or a diuretic in Japanese elderly hypertensive patients (COLM) trial demonstrated that olmesartan combinations with a CCB or diuretic have similar effects on reducing cardiovascular risk in elderly hypertensive patients. However, the safety profiles suggest that olmesartan combined with CCB may be preferable to olmesartan combined with diuretic. In this subgroup analysis, we further evaluated the effects and safety of these combinations in elderly (65–74 years old (y.o.)) and very elderly (75–84 y.o.) hypertensive patients. In the COLM trial, 5141 patients (2918 elderly and 2223 very elderly) were randomly assigned to receive olmesartan-based therapy with either CCB or diuretic. The hazard ratios and 95% confidence intervals, respectively, in the elderly age group and in the very elderly group were: 1.04 (0.72–1.50; olmesartan plus CCB vs. olmesartan plus diuretic, P=0.85) and 0.71 (0.51–0.99, P=0.045) for the primary composite end point, and 1.07 (0.67–1.72, P=0.77) and 0.64 (0.42–0.98, P=0.036) for the composite of hard end points. The hazard ratios for stroke (fatal and non-fatal) were 1.48 (0.88–2.48; olmesartan plus CCB vs. olmesartan plus diuretic, P=0.13) and 0.63 (0.39–1.02, P=0.059) (interaction-P=0.019). Withdrawal rates from the trial, withdrawal due to serious adverse event and the incidence of any adverse event were higher in the olmesartan plus diuretic group than in the olmesartan plus CCB group in both age groups. In conclusion, angiotensin receptor blocker (ARB) and CCB combination may be preferable to an ARB and diuretic combination in the very elderly hypertensive patients for the reduction of cardiovascular risk, particularly for the reduction in stroke risk.

Combinations of olmesartan and a calcium channel blocker or a diuretic in elderly hypertensive patients: a randomized, controlled trial.

Objective:The aim of the present study was to compare the cardiovascular effects of olmesartan, an angiotensin II receptor blocker, combined with a calcium channel blocker (CCB) or a diuretic, in a prospective, randomized, open-label, blinded endpoint trial.Methods:Japanese hypertensive patients aged at least 65 to less than 85 years with SBP at least 140 mmHg and/or DBP at least 90 mmHg with antihypertensive treatment, or SBP at least 160 mmHg and/or DBP at least 100 mmHg without antihypertensive treatment were randomized to receive olmesartan with either a dihydropyridine CCB or a low-dose diuretic. If SBP and/or DBP remained at least 140 and/or at least 90 mmHg, the other antihypertensive drug was added. The primary endpoint was a composite of fatal and nonfatal cardiovascular events. The median follow-up time was 3.3 years.Results:Blood pressure decreased similarly in both groups. The primary endpoint occurred in 116/2568 patients (4.5%) in the olmesartan plus CCB group and in 135/2573 patients (5.3%) in the olmesartan plus diuretic group [hazard ratio 0.83, 95% confidence interval (CI) 0.65–1.07, P = 0.16]. Rates of all-cause death and cardiovascular deaths were similar. Among patients aged at least 75 years, the incidence of stroke tended to be lower in the olmesartan plus CCB group than in the olmesartan plus diuretic group (hazard ratio 0.63, 95% CI 0.38–1.02, P = 0.059, interaction P = 0.019). Fewer patients in the olmesartan plus CCB group (8.2%, 211/2568) than in the olmesartan plus diuretic group (9.8%, 253/2573; P = 0.046) experienced serious adverse events.Conclusion:Despite no significant difference in cardiovascular events, the different safety profiles suggest that the combination of olmesartan and CCB may be preferable to that of olmesartan and diuretic.

Intratympanic Steroid Treatment for Acute Low‐Frequency Sensorineural Hearing Loss without Vertigo: Prospective Controlled Study

Objectives: Compare the effectiveness of treatment for acute low frequency sensorineural hearing loss (LFHL) with tinnitus and without vertigo between intratympanic dexamethasone injections (ITDI) and oral diuretics. Methods: A total of 35 tinnitus patients with LFHL that had developed within previous 2 weeks were enrolled and randomly assigned into 2 groups: (1) treated with ITDI 4 times on each of 4 consecutive days (19 patients) and (2) treated with diuretics orally for 2 weeks (16 patients). The group assignments and the process of treatments were double-blinded. After 8 weeks, we analyzed treatment outcomes of LFHL using subjective symptom score and audiometric change. Results: The cure rate of ITDI group (42.1%) was significantly higher than that of diuretics group (25.0%). For subjective symptom score, there were no statistically significant differences of improvement rate in both groups (ITDI 63.2%, diuretics 56.3%). In pure tone audiometry, the improvement rate of ITDI group (73.7%) was significantly higher than that of diuretics group (62.5%). There was a significant correlation between the cure rate and duration of symptoms. Conclusions: ITDI is a more effective treatment modality than oral diuretics for LFHL within 2 weeks of development. Duration of symptom affects the cure rate of acute LFHL with tinnitus and without vertigo.

A randomised controlled trial for the evaluation of risk for type 2 diabetes in hypertensive patients receiving thiazide diuretics: Diuretics In the Management of Essential hypertension (DIME) study

ObjectivesThiazide diuretics are one of the first choice antihypertensives but not optimally utilised because of concerns regarding their adverse effects on glucose metabolism. The Diuretics In the Management of Essential...