Hydrochlorothiazide Group Research Articles

MP90-04 A NOVEL USE OF STRUCTURED WATER FOR THE PREVENTION OF RECURRENT STONES IN IDIOPATHIC HYPERCALCIURIA.

You have accessJournal of UrologyStone Disease: Medical & Dietary Therapy1 Apr 2017MP90-04 A NOVEL USE OF STRUCTURED WATER FOR THE PREVENTION OF RECURRENT STONES IN IDIOPATHIC HYPERCALCIURIA. Ali Sami Ali SamiAli Sami More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2823AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The majority of stones (85%) contain primarily calcium oxalate. Most renal stones are idiopathic calcium stones, and the most common predisposing factor in these patients is hypercalciuria. Structured water is a new type of water that has been prepared using different types of energy fields and modulators to produce this structured water that has new and different characteristics from the ordinary water. In this study, we compared the efficacy of the structured water (Magnalife®) with hydrochlorothiazide and with ordinary bottled water in the prevention of recurrent renal stones in patients with idiopathic hypercalciuria. METHODS We conducted a three-year randomized trial comparing the effect of structured water with the effect of hydrochlorothiazide and ordinary bottled water in 300 patients with recurrent calcium oxalate stones and hypercalciuria. 100 men used structured water (Magnalife®). The other 100 men used 50 mg hydrochlorothiazide, and 100 men used ordinary bottled water. Urine analysis with renal ultrasonography and radiology were done at baseline and at yearly intervals and any time of recurrence and at the end of the 3 years (36th month). All patients were informed and signed a written informed consent form. RESULTS Of the 300 men included in this study, 95 had recurrent stones, 15 men (15%) in the group of structured water ,31 men (31%) in the hydrochlorothiazide group, and 49 men (49%) in the group of ordinary bottled water. The difference in the recurrence rate between the structured water group and the hydrochlorothiazide group is significant (P=0.007) Also the difference between the difference between the structured water group and the ordinary water group is significant (p<0.001), furthermore the hydrochlorothiazide group and the ordinary bottled water group recurrence rate is significantly different (P=0.009). CONCLUSIONS Structured water is a safe, effective, and affordable new way to prevent recurrent urinary stones without the need for medications that are expensive and have many side effects. Furthermore, it is more potent than some preventive measures and drugs as a prophylactic way against recurrent urinary stones. It is far more effective than ordinary bottled water in preventing recurrent stones. Further studies are recommended to explore its role in other fields of urology. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1211 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ali Sami More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Итоги международного клинического исследования VICTORY: эффективность и безопасность антигипертензивной монотерапии валсартаном (Вальсакор®) и его фиксированной комбинации с гидрохлоротиазидом (Вальсакор® Н) у пациентов с артериальной гипертонией 1–2-й степени в рутинной клинической практике

Objective. The VICTORY study aimed to evaluate effectiveness and safety of monotherapy with valsartan (Valsacor®) and its fixed combination with hydrochlorothiazide (Valsacor® H) in clinical practice in patients with stage 1 and stage 2 hypertension. Materials and methods. In the prospective, randomized, open-label, international multicentre study involved 356 patients with grade 1 and grade 2 hypertension from 5 countries, including 130 patients from Russia. In Russia the study was conducted in 7 cities, in 8 clinical centers. The patients, who were receiving antihypertensive therapy at the moment of screening, underwent a 7 days wash-out period. The starter dose of valsartan (Valsacor®, KRKA, Slovenia) was 80 mg (except for Russia where 160 mg of Valsacor® were given at the first visit, what did not influence the study results). After 4 weeks of treatment in case of blood pressure (BP) >140/90 or 130/80 mm Hg the dose was increased to 160 mg (in Russia - to 320 mg) or combined therapy with Valsacor® H (KRKA, Slovenia) was prescribed. In 4 weeks the dose of valsartan was increased to 320 or 160/12.5 mg in case of previous dose insufficiency. If target BP levels were not reached in the next 4 weeks, the dose was increased to 320/12.5 mg. The primary endpoints included evaluation of antihypertensive effect of valsartan and its fixed combination with hydrochlorothiazide on BP levels; evaluation of the drugs’ influence on aortal stiffness; comparison of absolute average means of achieved decrease in central and peripheral BP compared with baseline; evaluation of the impact on aortic augmentation index. The secondary endpoints included comparison of primary endpoints when using mono and combined therapy; evaluation and comparison of the effect on erectile function in men by questionnaires at baseline and after 16 weeks of treatment; evaluation of adverse events frequency. Results. Data on 365 patients - 196 (54.0%) female and 169 (46.0%) male aged 54.6±12.0 years were analyzed. Mean initial value of systolic (SBP) and diastolic BP (DBP) were 156.6±8.9 and 95.6±6.0 mm Hg, respectively and 130.1±8.2 and 80.9±5.8 mm Hg, respectively after 16 weeks of treatment. The mean absolute decrease of SBP and DBP was 26.6±10.4 and 14.8±7.6 mm Hg. The decrease of SBP and DBP was statistically significant in all treatment periods (p<0,0001). The mean absolute decrease of central SBP and DBP at the 5th visit was 19.7±12.9 and 13.9±8.5 mm Hg, respectively (p<0.0001). When compared, the mean values of SBP and DBP between groups of mono and combined therapy were statistically significant (p<0.0001). 90,6% of patients reached the target BP levels: 98% in those who received monotherapy with valsartan and 84% in those who received combination of valsartan and hydrochlorothiazide. The mean absolute increase of erectile function score was 0.84±2.45 (p<0.0001). There were no differences in erectile function score dynamics in the two groups of patients. 92.8% of patients did not experience adverse effects and adverse events associated with the medication. There were no cases of severe adverse events in the study. The most frequent adverse effects were headache (1.9%), dizziness (1.6%), and weakness (1.6%). Conclusion. The study demonstrated high effectiveness and good tolerability of valsartan and its fixed combination with hydrochlorothiazide (Valsacor®, Valsacor® H) in patients with stage 1 and stage 2 hypertension. 1. Valsartan in monotherapy (Valsacor®) and in combination with hydrochlorothiazide (Valsacor® H) lowers the SBP and DBP levels to reference levels. 2. At the 16th week of treatment 90.6% reached target BP levels: 98% in the valsartan monotherapy group and 84% in the combination therapy with valsartan and hydrochlorothiazide group. 3. The medications Valsacor® and Valsacor® H have good tolerability: 92.8% of the patients did not experience any adverse effects. 7.1% of patients had at least 1 adverse effect but none of them experienced any severe adverse events. 4. The therapeutic effect was estimated as good and very good in 96.9% of patients. 5. The overall clinical effectiveness was estimated as excellent, very good and good in 95.3% of patients. 6. Most of the patients receiving Valsacor® and Valsacor® H noted an increase in life quality. 7. Treatment with Valsacor® and Valsacor® H resulted in increase of erectile function in male patients with stage 1 and stage 2 hypertension.

Cost-effectiveness of nitrendipine and hydrochlorothiazide or metoprolol to treat hypertension in rural community health centers in China.

The objective of this article is to compare blood pressure (BP)-lowing effects of nitrendipine and hydrochlorothiazide and nitrendipine and metoprolol, and estimate the economic effect of these therapies on hypertension. Outpatients (N = 793) 18-70 years of age with stage 2 or severe hypertension (SBP ≥ 160 mmHg and/or DBP ≥ 100 mmHg) were recruited from four randomly selected rural community health centers in Beijing and Jilin. After drug wash out, they were randomly divided into nitrendipine and hydrochlorothiazide group or nitrendipine and metoprolol group. The costs of drug treatment for hypertension were calculated and general estimation, whereas effectiveness was measured as a reduction in SBP and DBP at the end of a 24-week study period. Overall, 623 patients were eligible for the study and after a 24-week follow-up, SBP and DBP were 131.2/82.2 mmHg for the nitrendipine and hydrochlorothiazide group and 131.4/82.9 mmHg for the nitrendipine and metoprolol group and these were not significantly different (P = 0.7974 SBP and P = 0.1166 DBP). Comparing with nitrendipine and metoprolol, the cost of nitrendipine and hydrochlorothiazide was less, and its effectiveness was similar. The cost/effect ratio (US$/mmHg) was 1.4 for SBP and 2.8 for DBP for the nitrendipine and hydrochlorothiazide group, and 1.9 and 3.8 for the nitrendipine and metoprolol group's SBP and DBP values, respectively. The incremental cost per patient for achieving target BP was 5.1. Adverse events were mild or moderate and there were no differences between treatment groups. Treating hypertension with nitrendipine and hydrochlorothiazide was cost-effective than nitrendipine and metoprolol, and these data will allow more reasonable and efficient allocation of limited resources in low-income countries.

Angiotensin II receptor blocker combined with eplerenone or hydrochlorothiazide for hypertensive patients with diabetes mellitus

ABSTRACTExperimental models recently suggested an interaction between aldosterone and adipose tissue, but clinical investigation has been limited. We studied the effects of eplerenone compared to hydrochlorothiazide (HCTZ) on blood pressure (BP), glucose, and lipid levels in 50 patients with essential hypertension (EHT) and type 2 diabetes mellitus whose BP failed to reach target levels with 8 mg of candesartan alone. BP improved similarly in both groups over the 12-month study period, but BMI, waist circumference, and LDL-cholesterol were decreased in the eplerenone group, while glycohemoglobin was elevated in the HCTZ group.

Controlled diuretic monotherapy in hypertensive patients: Efficiency and metabolic safety

To evaluate the antihypertensive efficiency and metabolic effects of controlled monotherapy with hydrochlorothiazide (HCT) and indapamide retard (IR) in hypertensive patients. The study included 50 patients with Stage II essential hypertension, grades 1-3 blood pressure (BP) elevation, who received 3-month monotherapy with IR (n=25) or HCT (n=25). Changes were determined in BP, blood lipid, glucose, and potassium levels. The efficiency of antihypertensive therapy was evaluated in the entire group and subgroups of patients identified in accordance with the used diuretic and the presence (n=27) or absence (n=23) of therapy at previous stages. A total of 54% of the patients included in the study achieved target BP after 3 months of therapy. The proportion of individuals with normalized BP was comparable in the HCT and IR groups (52 and 56%, respectively) and in previously treated patients and those who used for the first time antihypertensive drugs (51.8 and 56.5%, respectively). Normalization of systolic and diastolic BPs was achieved in 78 and 58% of the patients, respectively. Target BP was achieved in 94,1%, 42,9% and 16,7% of patients with grades 1,2 and 3 hypertension, respectively. IR proved to be metabolically neutral whereas HCT was found to significantly increase the blood levels of triglycerides and glucose by 15.3% (p<0.05) and 12.2% (p<0.05), respectively. Controlled diuretic monotherapy allows BP normalization in more than 50% of the hypertensive patients. HCT and IR have similar antihypertensive efficiency. Because of the negative changes observed in lipid and carbohydrate metabolism with the use of relatively small doses of HCT, IR is a preferential alternative in the long-term treatment of hypertensive patients.

Ramipril + amlodipine and ramipril + hydrochlorothiazide fixed-dose combinations in relation to patient adherence.

ObjectiveTo compare 1-year treatment adherence of ramipril + amlodipine and ramipril +hydroclorothiazide fixed-dose combination therapies in patients with hypertension.MethodsData were extracted from the database of the National Health Insurance Fund of Hungary. Treatment adherence was modelled using survival analysis.ResultsAt 2 months after initiation of treatment, 42% of patients using ramipril +hydrochlorothiazide (n = 28,800) had discontinued treatment, compared with 0% of patients using ramipril + amlodipine (n = 10,295). At 1 year, treatment adherence was 29% in the ramipril + hydrochlorothiazide group and 54% in the ramipril + amlodipine group. The hazard ratio for discontinuing ramipril + hydrochlorothiazide vs ramipril + amlodipine was 2.318 (95% confidence intervals 2.246, 2.392).ConclusionRamipril + amlodipine had significantly higher 1-year treatment adherence than ramipril + hydrochlorothiazide in patients with hypertension.

Efficacy of Low-Dose Chlorthalidone and Hydrochlorothiazide as Assessed by 24-h Ambulatory Blood Pressure Monitoring

BackgroundThiazide and thiazide-like diuretic agents are being increasingly used at lower doses. Hydrochlorothiazide (HCTZ) in the 12.5-mg dose remains the most commonly prescribed antihypertensive agent in the United States. ObjectivesThis study compared chlorthalidone, 6.25 mg daily, with HCTZ, 12.5 mg daily, by 24-h ambulatory blood pressure (ABP) monitoring and evaluated efficacy. Because HCTZ has been perceived as a short-acting drug, a third comparison with an extended-release formulation (HCTZ-controlled release [CR]) was added. MethodsThis 12-week comparative, double-blind, outpatient study randomized 54 patients with stage 1 hypertension to receive either chlorthalidone, 6.25 mg, (n = 16); HCTZ 12.5 mg (n = 18); or HCTZ-CR 12.5 mg (n = 20). ABP monitoring was performed at baseline and after 4 and 12 weeks of therapy. ResultsAll 3 treatments significantly (p < 0.01) lowered office BP at weeks 4 and 12 from baseline. At weeks 4 and 12, significant reductions in systolic and diastolic 24-h ambulatory and nighttime BP (p < 0.01) were observed with chlorthalidone but not with HCTZ. At weeks 4 (p = 0.015) and 12 (p = 0.020), nighttime systolic ABP was significantly lower in the chlorthalidone group than in the the HCTZ group. With HCTZ therapy, sustained hypertension was converted into masked hypertension. In contrast to the HCTZ group, the HCTZ-CR group also showed a significant (p < 0.01) reduction in 24-h ABP. All 3 treatments were generally safe and well tolerated. ConclusionsTreatment with low-dose chlorthalidone, 6.25 mg daily, significantly reduced mean 24-h ABP as well as daytime and nighttime BP. Due to its short duration of action, no significant 24-h ABP reduction was seen with HCTZ, 12.5 mg daily, which merely converted sustained hypertension into masked hypertension. Thus, low-dose chlorthalidone, 6.25 mg, could be used as monotherapy for treatment of essential hypertension, whereas low-dose HCTZ monotherapy is not an appropriate antihypertensive drug. (Comparative Evaluation of Safety and Efficacy of Hydrochlorothiazide CR with Hydrochlorothiazide and Chlorthalidone in Patients With Stage I Essential Hypertension; CTRI/2013/07/003793)

Relationship Between Changes in Serum Urate and Bone Mineral Density During Treatment with Thiazide Diuretics: Secondary Analysis from a Randomized Controlled Trial.

In observational studies, serum urate concentrations associate with bone mineral density (BMD) and reduced risk of fractures. Thiazide diuretics slow the bone loss in healthy older adults, are associated with reduced incidence of fracture and also increase serum urate. We hypothesized that changes in serum urate are associated with changes in BMD during treatment with thiazide diuretics. We analysed data from a double-blind randomized controlled trial of hydrochlorothiazide (50mg per day) and placebo in normal post-menopausal women. The relationship between change in serum urate and change in BMD after 2years of treatment was examined using Spearman correlation and multiple linear regression models. Total body BMD increased in the hydrochlorothiazide group by 0.52% and reduced in the placebo group by 0.29% over 2years (between group difference P=0.0034). Serum urate increased in the hydrochlorothiazide group by 0.038mmol/L and reduced in the placebo group by 0.004mmol/L (between group difference P<0.0001). At Year 2, there was a positive relationship between the change in serum urate and change in total body BMD for entire study population (r=0.32, P=0.0002) and for the hydrochlorothiazide group (r=0.29, P=0.023). The association between change in serum urate and change in total body BMD persisted after adjusting for treatment allocation, and change in weight, serum calcium, urinary calcium and serum creatinine (P change in serum urate=0.043). These data raise the possibility that the effects of hydrochlorothiazide on BMD may be mediated, in part, by changes in serum urate concentrations.

Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3): a parallel-group, double-blind randomised phase 4 trial

SummaryBackgroundPotassium depletion by thiazide diuretics is associated with a rise in blood glucose. We assessed whether addition or substitution of a potassium-sparing diuretic, amiloride, to treatment with a thiazide can prevent glucose intolerance and improve blood pressure control.MethodsWe did a parallel-group, randomised, double-blind trial in 11 secondary and two primary care sites in the UK. Eligible patients were aged 18–80 years; had clinic systolic blood pressure of 140 mm Hg or higher and home systolic blood pressure of 130 mmHg or higher on permitted background drugs of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β blockers, calcium-channel blockers, or direct renin inhibitors (previously untreated patients were also eligible in specific circumstances); and had at least one component of the metabolic syndrome in addition to hypertension. Patients with known diabetes were excluded. Patients were randomly assigned (1:1:1) to 24 weeks of daily oral treatment with starting doses of 10 mg amiloride, 25 mg hydrochlorothiazide, or 5 mg amiloride plus 12·5 mg hydrochlorothiazide; all doses were doubled after 12 weeks. Random assignment was done via a central computer system. Both participants and investigators were masked to assignment. Our hierarchical primary endpoints, assessed on a modified intention-to-treat basis at 12 and 24 weeks, were the differences from baseline in blood glucose measured 2 h after a 75 g oral glucose tolerance test (OGTT), compared first between the hydrochlorothiazide and amiloride groups, and then between the hydrochlorothiazide and combination groups. A key secondary endpoint was change in home systolic blood pressure at 12 and 24 weeks. This trial is registered with ClinicalTrials.gov, number NCT00797862, and the MHRA, Eudract number 2009-010068-41, and is now complete.FindingsBetween Nov 18, 2009, and Dec 15, 2014, 145 patients were randomly assigned to amiloride, 146 to hydrochlorothiazide, and 150 to the combination group. 132 participants in the amiloride group, 134 in the hydrochlorothiazide group, and 133 in the combination group were included in the modified intention-to-treat analysis. 2 h glucose concentrations after OGTT, averaged at 12 and 24 weeks, were significantly lower in the amiloride group than in the hydrochlorothiazide group (mean difference −0·55 mmol/L [95% CI −0·96 to −0·14]; p=0·0093) and in the combination group than in the hydrochlorothiazide group (−0·42 mmol/L [–0·84 to −0·004]; p=0·048). The mean reduction in home systolic blood pressure during 24 weeks did not differ significantly between the amiloride and hydrochlorothiazide groups, but the fall in blood pressure in the combination group was significantly greater than that in the hydrochlorothiazide group (p=0·0068). Hyperkalaemia was reported in seven (4·8%) patients in the amiloride group and three (2·3%) patients in the combination group; the highest recorded potassium concentration was 5·8 mmol/L in a patient in the amiloride group. 13 serious adverse events occurred but the frequency did not differ significantly between groups.InterpretationThe combination of amiloride with hydrochlorothiazide, at doses equipotent on blood pressure, prevents glucose intolerance and improves control of blood pressure compared with montherapy with either drug. These findings, together with previous data about morbidity and mortality for the combination, support first-line use of amiloride plus hydrochlorothiazide in hypertensive patients who need treatment with a diuretic.FundingBritish Heart Foundation and National Institute for Health Research.

Central integration and neural control of blood pressure during the cold pressor test: a comparison between hydrochlorothiazide and aliskiren.

Individuals with hypertension and sympathetic overactivity are at risk for cardiovascular events. Renin inhibitors are new while thiazide diuretics are first-class drugs used for treatment of hypertension. The purpose of this study was to determine whether 6 months of treatment with aliskiren (ALSK) or hydrochlorothiazide (HCTZ) would alter blood pressure (BP) and muscle sympathetic nerve activity (MSNA) indices in older mild hypertensives during a cold pressor test (CPT). We hypothesized that the ALSK group would demonstrate a blunted response compared to HCTZ. Nineteen (9 men, 10 women) subjects performed a CPT pre- and post treatment where heart rate (HR), systolic BP (SBP) and diastolic BP (DBP), and MSNA were measured. Blood samples were withdrawn for assessment of renal-adrenal hormones. Both medications lowered ambulatory SBP and DBP (P < 0.05). Direct renin tended to be higher in the ALSK group after treatment (P = 0.081). Aldosterone was higher in the HCTZ group after treatment (P < 0.001). As expected, both groups showed increases in HR, SBP, DBP, and MSNA during the CPT (all P < 0.05). All cardiovascular and MSNA responses were similar pre- and post treatment in both groups (peak CPT SBP: 26 ± 10 vs. 17 ± 21 and 21 ± 20 vs. 29 ± 15 mmHg for pre vs. post for HCTZ and ALSK, respectively; peak CPT MSNA burst frequency: 13 ± 8 vs. 11 ± 11 and 11 ± 17 vs. 6 ± 13 bursts/min; all P > 0.05). Treatment with these antihypertensive medications lowered BP but was not successful in lowering the responsiveness to the CPT.

Triamterene Enhances the Blood Pressure Lowering Effect of Hydrochlorothiazide in Patients with Hypertension.

Triamterene, because of its potassium-sparing properties, is frequently used in combination with hydrochlorothiazide (HCTZ) to treat patients with hypertension. By inhibiting the epithelial sodium channel (ENaC) in the cortical collecting duct, triamterene reduces potassium secretion, thus reducing the risk of hypokalemia. Whether triamterene has an independent effect on blood pressure (BP) has not been well studied. To determine if triamterene provides an effect to further lower BP in patients treated with HCTZ. We conducted an observational study using electronic medical record data from the Indiana Network for Patient Care. Participants were 17,291 patients with the diagnosis of hypertension between 2004 and 2012. BP was the primary outcome. We compared the BP between patients who were taking HCTZ, with and without triamterene, either alone or in combination with other antihypertensive medications, by using a propensity score analysis. For each medication combination, we estimated the propensity score (i.e., probability) of a patient receiving triamterene using a logistic regression model. Patients with similar propensity scores were stratified into subclasses and BP was compared between those taking triamterene or not within each subclass; the effect of triamterene was then assessed by combining BP differences estimated from all subclasses. The mean systolic BP in the triamterene + HCTZ group was 3.8 mmHg lower than in the HCTZ only group (p < 0.0001); systolic BP was similarly lower for patients taking triamterene with other medication combinations. Systolic BP reduction was consistently observed for different medication combinations. The range of systolic BP reduction was between 1 and 4 mm Hg, depending on the concurrently used medications. In the present study, triamterene was found to enhance the effect of HCTZ to lower BP. In addition to its potassium-sparing action, triamterene's ability to lower BP should also be considered.

Comparative Effect of a Renin Inhibitor and a Thiazide Diuretic on Renal Tissue Oxygenation in Hypertensive Patients

Background/Aims: The purpose of the present study was to compare the direct renin inhibitor aliskiren to the diuretic hydrochlorothiazide (HCTZ) in their ability to modulate renal tissue oxygenation in hypertensive patients. Methods: 24 patients were enrolled in this randomized prospective study and 20 completed the protocol. Patients were randomly assigned to receive either aliskiren 150-300 mg/d or HCTZ 12.5 - 25 mg/d for 8 weeks. Renal oxygenation was measured by BOLD-MRI at weeks 0 and 8. BOLD-MRI was also performed before and after an i.v. injection of 20 mg furosemide at week 0 and at week 8. BOLD-MRI data were analyzed by measuring the oxygenation in 12 computed layers of the kidney enabling to asses renal oxygenation according to the depth within the kidney and by the classical method of regions of interest (ROI). Results: The classical ROI analysis of the data showed no difference between the groups at week 8. The analysis of renal oxygenation according to the 12 layers method shows no significant difference between aliskiren and HCTZ at week 8 before administration of furosemide. However, within group analyses show that aliskiren slightly but not significantly increased oxygenation in the cortex and decreased medullary oxygenation whereas HCTZ induced a significant overall decrease in renal tissue oxygenation. With the same method of analysis we observed that the response to furosemide was unchanged in the HCTZ group at week 8 but was characterized by an increase in both cortical and medullary oxygenation in aliskiren-treated patients. Patients responding to aliskiren and HCTZ by a fall in systolic blood pressure of >10 mmHg improved their renal tissue oxygenation when compared to non-responders. Conclusion: With the classical method of evaluation using regions no difference were found between aliskiren and HCTZ on renal tissue oxygenation after 8 weeks. In contrast, with our new method that takes into account the entire kidney, within group analyses show that aliskiren slightly increases cortical and medullary renal tissue oxygenation in hypertensive patients whereas HCTZ decreases significantly renal oxygenation at trough.

Effects of hydrochlorothiazide on oxidative stress and pulse pressure in hypertensive patients with chronic stroke: the EMINENT study.

Thiazide diuretics are reported to have antioxidant effects and reduce pulse pressure (PP). The aim of this study was to elucidate whether hydrochlorothiazide additionally exerts such effects in stroke patients under treatment with losartan. This study was an open-label, randomized, multicenter study. Patients with a history of chronic stroke and treatment with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors for essential hypertension were enrolled. Fifty-five hypertensive patients were randomly assigned to two groups: those further treated with hydrochlorothiazide and those further treated with non-diuretic antihypertensive drugs. Both groups showed a significant decrease in PP over six months (hydrochlorothiazide group: 67±12 mmHg to 58±12, p<0.001; non-diuretic group: 72±12 to 61±12, p<0.001), although no significant differences were observed between the two groups. The malondialdehyde-modified low-density lipoprotein levels did not change significantly after treatment in either group. In this study, hydrochlorothiazide treatment did not provide any additional benefits over non-diuretic antihypertensive drugs in terms of antioxidant effects or reducing PP.

Comparison of new-onset gout in adults prescribed chlorthalidone vs. hydrochlorothiazide for hypertension.

This study assessed the risk of new-onset gout following prescribing of hydrochlorothiazide (HCTZ) compared with chlorthalidone (CTD). This retrospective cohort analysis used administrative claims from 2000 to 2012 to identify patients aged 18 to 89years with hypertension who were prescribed CTD or HCTZ. Patients were excluded if they had a prior diagnosis of gout, conditions or prescription claims for medications that alter risk of gout, or if they switched between these two diuretics. A total of 1011 patients prescribed CTD were matched with 2022 patients prescribed HCTZ based on age, sex, and Chronic Condition Indicator. New-onset gout occurred in 17 of 1011 (1.68%) patients in the CTD group and in 26 of 2022 (1.29%) patients in the HCTZ group (P=.27). The number of days to first occurrence of gout was 183.6days and 152.7days in the CTD and HCTZ groups, respectively (P=.39). The mean daily dose was 22.7mg for CTD and 24.3mg for HCTZ, and the median dose of both CTD and HCTZ was 25mg at the time of new-onset gout. Patients prescribed CTD for hypertension have a similar risk of developing new-onset gout compared with patients prescribed similar doses of HCTZ.

Hemodynamic and metabolic effects of estrogen plus progestin therapy in hypertensive postmenopausal women treated with an ACE-inhibitor or a diuretic.

ObjectivesThe aim of the study was to assess the hemodynamic and metabolic actions of estrogen plus progestin therapy (EPT) in hypertensive, postmenopausal women treated with perindopril (ACEI) or hydrochlorothiazide (HCTZ). A group of normotensive postmenopausal women was also studied.Methods100 hypertensive and 40 normotensive postmenopausal women were recruited for the study. The hypertensive females were randomly assigned to receive ACEI or HCTZ for 12 months. The patients of the ACEI group and the patients of the HCTZ group, as well as normotensives, were further subdivided into two subgroups each. One subgroup received estrogen plus progestin therapy (EPT+), the other subgroup received no hormone replacement (EPT−). Combined hormone replacement with transdermal patches releasing 17β-estradiol and norethisterone was used. Office and 24-hour ambulatory blood pressure was measured at baseline and during follow-up. Renal plasma flow (RPF) was measured using the clearance of [125I]-iodohippuran. Pulse wave velocity (PWV) was determined with an automatic device.ResultsIn normotensive postmenopausal women, transdermal estrogen plus progestin therapy increases RPF and insulin sensitivity, decreases PWV, decreases total and LDL cholesterol, and decreases uric acid serum levels. Perindopril (4 mg/day) and hydrochlorothiazide (25 mg/day) were equally effective in reducing blood pressure in postmenopausal, hypertensive subjects. In these females, perindopril increased RPF and decreased PWV and plasma insulin levels. These effects of the ACEI were not altered by estrogen plus progestin therapy. Hydrochlorothiazide decreased RPF and increased plasma insulin and uric acid concentrations in hypertensive subjects whom were not receiving estrogen plus progestin therapy.ConclusionsThe unfavorable metabolic and hemodynamic actions of the diuretic were counteracted by estrogen plus progestin therapy. Concomitant estrogen plus progestin therapy may be a method to avoid unfavorable hemodynamic and metabolic effects of thiazide diuretics in hypertensive, postmenopausal women.

Mineralocorticoid receptor blockade improves coronary microvascular function in individuals with type 2 diabetes.

Reduced coronary flow reserve (CFR), an indicator of coronary microvascular dysfunction, is seen in type 2 diabetes mellitus (T2DM) and predicts cardiac mortality. Since aldosterone plays a key role in vascular injury, the aim of this study was to determine whether mineralocorticoid receptor (MR) blockade improves CFR in individuals with T2DM. Sixty-four men and women with well-controlled diabetes on chronic ACE inhibition (enalapril 20 mg/day) were randomized to add-on therapy of spironolactone 25 mg, hydrochlorothiazide (HCTZ) 12.5 mg, or placebo for 6 months. CFR was assessed by cardiac positron emission tomography at baseline and at the end of treatment. There were significant and similar decreases in systolic blood pressure with spironolactone and HCTZ but not with placebo. CFR improved with treatment in the spironolactone group as compared with the HCTZ group and with the combined HCTZ and placebo groups. The increase in CFR with spironolactone remained significant after controlling for baseline CFR, change in BMI, race, and statin use. Treatment with spironolactone improved coronary microvascular function, raising the possibility that MR blockade could have beneficial effects in preventing cardiovascular disease in patients with T2DM.

SAT0529 Relationship between Changes in Serum Urate and Bone Mineral Density during Treatment with Thiazide Diuretics: Secondary Analysis from A Randomised Controlled Trial

BackgroundRecent observational studies have reported that serum urate (SU) concentrations positively correlate with bone mineral density (BMD), and that higher SU concentrations are associated with reduced risk of fractures. Thiazide...

176 Effects of Different Antihypertensive Pharmacological Treatments on the Cardiovascular Autonomic Control Evaluated by Different Experimental Approaches in Animal Model

IntroductionArterial hypertension is frequently accompanied by a lot of comorbidities, such as the changes in autonomic cardiovascular control. These changes, if not reversed, may be crucial for the development and...

Effects of the novel melanocortin receptor agonist bremelanotide on ambulatory blood pressure and heart rate in women with sexual dysfunction

Objective: To assess the risk of new-onset gout following the use of hydrochlorothiazide (HCTZ) compared to chlorthalidone (CTD) for hypertension in adult patients. Methods: We used the PharMetrics Integrated Database to conduct this retrospective cohort analysis using administrative claims from 2000 to 2012. Patients age 18 to 89 years old with hypertension that were prescribed HCTZ or CTD were identified. Patients were included if they had a hypertension diagnosis (ICD-9 code 401.xx) prior to the first prescription for HCTZ or CTD as well as continuous medical and prescription benefit eligibility throughout the 36 month study period (24 months before and 12 months after first prescription). Patients were excluded if they had prior diagnosis of gout, heart failure, stage IVor V chronic kidney disease, conditions that increase serum uric acid, prescription claims for medications known to increase or decrease serum uric acid, or if they switched between HCTZ and CTD. Patients prescribed CTD were matched 1:2 with patients prescribed HCTZ based on age, sex and Chronic Condition Index. A database analysis was performed to evaluate the following outcomes: 1) new-onset gout using ICD-9 codes and/or prescription claims for gout-specific medications, 2) number of days of HCTZ or CTD therapy until occurrence of new-onset gout, and 3) median HCTZ or CTD dose. Bivariate descriptive statistics and a time-to-event analysis were used to evaluate these data. Results: A total of 1011 patients prescribed CTD met eligibility criteria and were matched 1:2 with 2022 patients prescribed HCTZ. Baseline characteristics were similar between groups; 1584 (52%) were female and the average age was 55 years. New-onset gout occurred in 17 of 1011 (1.68%) in the CTD group and in 26 of 2022 (1.29%) patients in the HCTZ group (p 1⁄4 0.27). The number of days to first occurrence of gout was 183.6 and 152.7 days in the CTD and HCTZ groups, respectively (p 1⁄4 0.39). The mean daily dose of the first prescription was 22.7 mg for CTD and 24.3 mg for HCTZ, and the median dose of both CTD and HCTZ was 25mg at the time of new-onset gout. Conclusion: Patients prescribed typical doses of CTD for hypertension have a similar risk of developing new-onset gout compared to patients prescribed similar doses of HCTZ. These results support more wide-spread use of CTD for the management of hypertension.

Risk of Hypercalcemia in Blacks Taking Hydrochlorothiazide and Vitamin D

IntroductionHydrochlorothiazide, an effective antihypertensive medication commonly prescribed to blacks, decreases urinary calcium excretion. Blacks have significantly higher rates of hypertension and lower levels of 25-hydroxyvitamin D. Thus, they are more likely to be exposed to vitamin D supplementation and thiazide diuretics. The risk for hypercalcemia among blacks using vitamin D and hydrochlorothiazide is undefined. MethodsWe assessed the frequency of hypercalcemia in hydrochlorothiazide users in a post hoc analysis of a randomized, double-blind, dose-finding trial of 328 blacks (median age 51 years) assigned to either placebo, or 1000, 2000, or 4000 international units of cholecalciferol (vitamin D3) daily for 3 months during the winter (2007-2010). ResultsOf the 328 participants, 84 reported hydrochlorothiazide use and had serum calcium levels assessed. Additionally, a comparison convenience group of 44 enrolled participants who were not taking hydrochlorothiazide had serum calcium measurements at 3 months, but not at baseline. At 3 months, hydrochlorothiazide participants had higher calcium levels (0.2 mg/dL, P <.001) than nonhydrochlorothiazide participants, but only one participant in the hydrochlorothiazide group had hypercalcemia. In contrast, none of the nonhydrochlorothiazide participants had hypercalcemia. In a linear regression model adjusted for age, sex, 25-hydroxyvitamin D at 3 months, and other covariates, only hydrochlorothiazide use (Estimate [SE]: 0.05 [0.01], P = .01) predicted serum calcium at 3 months. ConclusionIn summary, vitamin D3 supplementation up to 4000 IU in hydrochlorothiazide users is associated with an increase in serum calcium but a low frequency of hypercalcemia. These findings suggest that participants of this population can use hydrochlorothiazide with up to 4000 IU of vitamin D3 daily and experience a low frequency of hypercalcemia.