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Background: Thiazide may have beneficial effects on bone mineral density and may reduce risk for hip fracture. However, the existence of a causal role remains uncertain because experimental evidence is limited. Objective: To determine the effect of hydrochlomthiazide on rates of bone loss in older adults. Design: Randomized, double-blind, placebo-controlled trial with 3-year follow-up. Setting: A large health maintenance organization in western Washington State. Participants: 320 healthy, normotensive adults (205 women, 115 men) 60 to 79 years of age. Intervention: Random assignment to one of three study groups: 12.5 mg of hydrochlorothiazide per day, 25 mg of hydrochlorothiazide per day, or placebo. Measurements: Bone mineral density using dual-energy x-ray absorptiometry at the total hip, posterior-anterior spine, and total body; blood and urine markers of bone metabolism; incident falls, clinical fractures, and radiographic vertebral fractures. Results: 309 of 320 participants completed the 36-month visit (97%). Adherence to study medication throughout follow-up was high in all participants (81.6% to 89.7%) except men in the high-dose hydrochlorothiazide group (60.5%). According to intention-to-treat analysis, the 36-month differences in percentage change in total hip bone mineral density were 0.79 percentage point (95% CI, -0.12 to 1.71) for the 12.5-mg hydrochlorothiazide group and 0.92 percentage point (CI, -0.001 to 1.85) for the 25-mg group compared with placebo (P = 0.03). Percentage change at the posterior-anterior spine was significantly greater for the 25-mg hydrochlorothiazide group at 6 months (intergroup difference, 1.04 percentage points [CI, 0.22 to 1.86]) compared with placebo (P = 0.005); at 36 months, this difference was 0.82 percentage point (CI, -0.36 to 2.01; P = 0.12). No significant differences were seen in total-body bone mineral density between the treatment groups. Treatment effects were stronger in women than in men. Conclusions: In healthy older adults, low-dose hydrochlorothiazide preserves bone mineral density at the hip and spine. The modest effects observed over 3 years, if accumulated over 10 to 20 years, may explain the one-third reduction in risk for hip fracture associated with thiazide in many epidemiologic studies.

Abstract Objective: To compare the effectiveness and tolerability of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in patients with mild to moderate hypertension. Design: Randomised multicentre trial over 48 weeks with double [...]

Background: Angiotensin II acts at the cellular level through specific angiotensin II subtype I, AT-1 receptors. Losartan is the first of a new class of antihypertensive agents that specifically block angiotensin II at AT-I receptors. By acting on complementary and different pharmacologic mechanisms, the concomitant use of low doses of hydrochlorothiazide with losartan may offer an additive antihypertensive activity with fewer adverse experiences. Methods: This double-blind study evaluated losartan concomitantly administered with hydrochlorothiazide as initial therapy in 703 patients with essential hypertension. Results: The greatest reduction in blood pressure was observed in the 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide group (17.2 mm Hg in sitting systolic blood pressure and 13.2 mm Hg in sitting diastolic blood pressure [P [less than or equal to].001], and the effects of the two components appeared to be additive. Seventy-eight percent of the patients treated with 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide had an excellent or good antihypertensive response (sitting diastolic blood pressure

The aim of this trial was to study the treatment of hypertension in the elderly, comparing a new oxazoline antihypertensive agent, rilmenidine, with the diuretic hydrochlorothiazide (HCZ). After 2 weeks on placebo, 88 elderly patients (mean age 75 years; 65 women), corresponding to strict inclusion criteria, were randomized to 8 weeks double-blind monotherapy with rilmenidine 1--2 mg/day (n = 46) or HCZ 25--50 mg/day (n = 42), with administration of potassium supplements as required. Particular emphasis was placed on the evaluation of safety: blood screens were repeated after 2, 4, and 8 weeks of treatment and symptoms were systematically evaluated every 2 weeks. The rilmenidine and HCZ groups were comparable at randomization, with baseline supine systolic/diastolic blood pressures of 167/101 mm Hg and 172/101 mm Hg, respectively. Both drugs induced a significant decrease in blood pressure: at 8 weeks, supine blood pressure had decreased to 154/89 mm Hg and to 155/87 mm Hg in the rilmenidine and HCZ groups, respectively (difference not significant between groups). Changes in heart rate did not differ significantly between groups ( -- 3 bpm at 8 weeks). Drug-related symptoms were rare and the incidence was similar in both groups. Weight decreased significantly in the HCZ group by 1 kg (p

Background: The safety and effectiveness of different dosages and combinations of antihypertensive agents can be efficiently studied using a multifactorial trial design, In consultation with the Cardio-Renal Division of the Food and Drug Administration, we conducted a randomized, double-blind, placebo-controlled, 3x4 factorial trial of bisoprolol, a [[beta].sub.1]-selective adrenergic blocking agent, and hydrochlorothiazide. Methods: A total of 512 patients with mild to moderate essential hypertension were randomized to once-daily treatment with bisoprolol (0, 2.5, 10, or 40 mg), hydrochlorothiazide (0, 6.25, or 25 mg), and all possible combinations. Diastolic and systolic blood pressures were monitored during this 12-week trial. Results: The effects of bisoprolol and hydrochlorothiazide were additive with respect to reductions in diastolic and systolic blood pressures over the dosage ranges studied. The addition of hydrochlorothiazide (or bisoprolol) to therapy with bisoprolol (or hydrochlorothiazide) produced an incremental reduction in blood pressure. Dosages of hydrochlorothiazide as low as 6.25 mg/d contributed a significant antihypertensive effect. A hydrochlorothiazide dosage of 6.25 mg/d produced significantly less hypokalemia and less of an increase in uric acid levels than a dosage of 25 mg/d. The low-dose combination of bisoprolol, 2.5 mg/d, and hydrochlorothiazide, 6.25 mg/d, reduced diastolic blood pressure to lower than 90 mm Hg in 61% of patients and demonstrated a safety profile that compared favorably with that of placebo. Conclusions: The utility of factorial design trials to characterize dose-response relationships and to test the potential interactions between various antihypertensive agents has been demonstrated. The combination of low dosages of bisoprolol and hydrochlorothiazide may be a rational alternative to conventional stepped-care therapy for the initial treatment of patients with mild to moderate hypertension.

The importance of concomitant low-dose hydrochlorathiazide was assessed in black hypertensive patients treated with enalapril. Left ventricular (LV) mass and function, metabolic perameters, 24-hour ambulatory blood pressure (BP), exercise duration, and systolic BP response were evaluated before and after drug therapy. Enalapril 20 mg (group 1) or enalapril 20 mg plus hydrochlorothiazide 12.5 mg (single tablet; group 2) was given to 38 patients for 9 weeks in a double-blind, placebo-controlled, randomized study. LV mass measured 61 [+ or -] 17 versus 102 [+ or -] 23 g/[m.sup.2], and 24-hour ambulatory BP measured 120 [+ or -] 8/7S [+ or -] 6 versus 155 [+ or -] 12/100 [+ or -] 6 mm Hg in matched control subjects (n = 40) versus hypertensive patients, respectively. No clinically important changes occurred in total cholesterol, serum uric acid or potassium in either group. Enalapril slightly reduced 24-hour ambulatory BP from 154 [+ or -] 15/100 [+ or -] 7 mm Hg to 148 [+ or -] 19/96 [+ or -] 11 mm Hg after treatment (p

Ventricular arrhythmias occur frequently in patients with hypertensive left ventricular (LV) hypertrophy and have been associated with increased incidence of sudden death. In this study, the effect of various antihypertensive medications on ventricular arrhythmias was evaluated in 31 hypertensive patients with moderate to severe LV hypertrophy. Patients were assessed at baseline (after 3 weeks of placebo treatment) and after treatment with each of 4 monotherapies: diltiazem 120 or 240 mg/day, metoprolol 100 or 200 mg/day, enalapril 10 or 20 mg/day and hydrochlorothiazide 50 or 100 mg/day. Each drug therapy was administered for 4 weeks. The sequence of each treatment was determined at random. Echocardiographic measurements and electrocardiograms were obtained only at baseline. Biochemical measurements and 48-hour Holter monitoring were obtained at baseline and at the end of each treatment. All treatments resulted in a significant but similar decrease in blood pressure. In the group as a whole diltiazem decreased ventricular premature complexes (VPCs) by 65% (p

To investigate whether sodium restriction might replace thiazides in promoting blood pressure (BP) reduction by angiotensin-converting enzyme inhibitors, the long-term hemodynamic effect of lisinopril plus sodium restriction versus lisinepril plus hydrochlorothiazide was compared at rest and during dynamic exercise in 2 groups of essential hypertensive patients. Mean pretreatment intraarterial BP at rest sitting was 177/107 mm Hg. The patients were randomly allocated to lisinopril combined with either low salt diet (low salt group, n = 13) or hydrochlorothiazide diuretic group, n = 12). After 1 year of treatment the mean dose of lisinopril was 2S mg in both groups. in the low salt group sodium excretion was reduced from 188 to 129 mmol/24 hours (p (Am J Cardiol 1990;65:331-338), Diuretic treatment reduces both salt and body fluid volume, and is currently a major treatment for high blood pressure. The thiazide diuretics are commonly used, often in combination with sodium-restriction or treatment with angiotensin-converting enzyme inhibitors. However, the thiazide diuretics are not without their own unwanted side effects. Therefore, 25 hypertensive patients participated in the evaluation of a salt-restricted diet in combination with the angiotensin-converting enzyme inhibitor, lisinopril, as an alternative to lisinopril with the diuretic hydrochlorothiazide. After one year, the 13 patients treated with lisinopril and the low-salt diet achieved a 16 percent reduction in average blood pressure, while a 21 percent reduction was observed for the patients taking lisinopril and the diuretic. The blood pressure reductions during exercise were a bit less; 10 percent and 13 percent for the low-salt and the diuretic patients, respectively. The mean heart output was reduced only for the patients taking the diuretic, suggesting that lisinopril and a salt-free diet provide a more complete normalization of blood flow. While both regimens resulted in effective reduction in blood pressure, lisinopril in combination with the low-salt diet reduces the risk of the unwanted side effects seen with diuretics, and should be the first choice for patients in whom successful blood pressure control is achieved. (Consumer Summary produced by Reliance Medical Information, Inc.)

The combination of an angiotensin receptor blocker plus hydrochlorothiazide is a more cost-effective treatment for hypertension than an angiotensin receptor blocker alone, Daniel E. Hilleman, Pharm.D., said in a poster [...]

The effect of cilazapril as monotherapy or in combination with hydrochlorothiazide wall assessed in 30 severely hypertensive patients, 23 men and seven women, aged 38 to 68 years, with sitting diastolic blood pressure of more than 115 mmHg. Fifteen patients had left ventricular hypertrophy documented by two-dimensional echocardiography. Sitting systolic blood pressure was reduced from 175.8 [+ or -] 2.0 to 143.3 [+ or -] 3.0 mmhg within 25 days of therapy (p, The effects of cilazapril with or without hydrochlorothiazide were examined in 30 patients with severe hypertension, or abnormally high blood pressure. The patient group was comprised of 23 men and seven women, aged 38 to 68 years. Sitting systolic blood pressure is the pressure during the contraction phase of the heart cycle recorded while sitting. The sitting diastolic blood pressure, which is the blood pressure during the relaxation phase of the heart cycle recorded while sitting, was 115 millimeters of mercury (mm Hg) in 23 patients. Fifteen patients had hypertrophy or enlargement of the left ventricle. An average dose of 10 milligrams (mg) of cilazapril with 12.5 to 25 mg of hydrochlorothiazide was effective in 90 percent of patients. Sitting systolic blood pressure was reduced from about 176 mm Hg to 143 mm Hg, while sitting diastolic blood pressure was reduced from 117 mm Hg to 88 mm Hg. Heart rate was unchanged. In 19 patients treated for 48 weeks, blood pressure remained lowered for a long-term period. Cilazapril decreased the mass of the left ventricle in nine patients with hypertrophy; this was correlated with the decrease in systolic blood pressure. Cilazapril improved the rate at which the ventricle fills with blood, but had no effect on blood flow in the kidney. The results demonstrate that the new antihypertensive agent cilazapril, combined with the currently used antihypertensive drug hydrochlorothiazide, is effective in treating patients with severe hypertension. In addition, the improvement of left ventricle hypertrophy was associated with improved left ventricle function. (Consumer Summary produced by Reliance Medical Information, Inc.)

The effect of cilazapril, a new inhibitor of angioctensin-converting enzyme, in a dosage of 2.5 or 5 mg once daily, was compared with that of hydrochlorothiazide 25 or 50 mg in 169 patients with mild to moderate hypertension. Blood pressure at entry was 158/103 mm Hg (cilazapril) and 160/103 mm Hg (hydrochlorothiazide). Cilazapril 2.5 mg caused a decrease in blood pressure of 14.7 [+ or -] 2.3/12.6 [+ or -] 1.2 mm Hg compared with a decrease of 12.6 [+ or -] 2.2/10.2 [+ or -] 1.2 mm Hg with hydrochlorothiazide 25 mg. Those patients who required an increase of dosage to the higher level then showed decreases of 15.0 [+ or -] 2.1/14.3 [+ or -] 1.2 (cilazapril) and 19.7 [+ or -] 1.9/13.3 [+ or -] 1.2 hydrochlorothiazide. All decreases in blood pressure were statistically significant but were not statistically different from each other. Fifty-one percent of patients reached a sitting diastolic blood pressure of 90 mm Hg or less receiving 2.5 mg of cilazapril and an additional 28 percent of patients reached this goal receiving 5 mg. The figures for patients receiving hydrochlorothiazide were comparable: 36 and 35 percent. Twenty-one adverse events remotely, possibly, or probably related to therapy were reported with cilazapril and 32 with hydrochlorothiazide. Three patients withdrew from cilazapril because of mild angioedema, headaches, and chest pain, respectively, and three patients withdrew from hydrochlorothiazide treatment because of fatigue, dizziness, and gastric hemorrhage. Hydrochlorothiazide caused a decrease in potassium levels and an increase in levels of cholesterol, uric acid, urea and -gamma cilazapril had no adverse biochemical effects. Cilazapril lowered blood pressure to the same extent as hydrochlorothiazide. Young patients had better responses to cilazapril than to hydrochlorothiazide. It is concluded that cilazapril is an effective and safe drug for patients with mild to moderate hypertension., The effectiveness of cilazapril was compared to that of hydrochlorothiazide in the treatment of 169 patients, aged 18 to 75 years, with mild to moderate essential hypertension, or abnormally high blood pressure of unknown cause. Sitting diastolic blood pressure is the pressure during the relaxation phase of the heart contraction cycle and is measured while the patient is sitting. A dose of 2.3 milligrams (mg) cilazapril decreased sitting diastolic blood pressure by about 15 millimeters mercury (mm Hg), whereas 25 mg of hydrochlorothiazide decreased sitting diastolic blood pressure by about 13 mm Hg. Cilazapril therapy was associated with 21 adverse events, whereas treatment with hydrochlorothiazide was associated with 32 unfavorable incidents. Three patients withdrew from cilazapril treatment because of mild angioedema, a skin disorder, headaches and chest pain, whereas three patients stopped hydrochlorothiazide treatment because of dizziness, fatigue, and stomach bleeding. Hydrochlorothiazide caused several changes in blood chemistry including a decrease in potassium and increase in cholesterol, whereas cilazapril had no adverse biochemical effects. The results demonstrate that cilazapril reduced blood pressure to the same extent as hydrochlorothiazide, and was also more effective in young patients. Cilazapril is an effective and safe agent for treating mild to moderate hypertension. (Consumer Summary produced by Reliance Medical Information, Inc.)

Laboratory studies performed on infants whose cause of death was abnormal development of the lungs (bronchopulmonary dysplasia), have revealed increased fluid levels within the lungs. This fluid collection may have been responsible for the poor lung function in these infants. Several experiments using diuretics to reduce excess fluid in the lungs have demonstrated improved pulmonary function. The use of diuretics, however, can cause a serious imbalance in the body's electrolytes. When the combination of the two diuretics, hydrochlorothiazide and spironolactone, are used there is less severe disruption of the electrolyte balance. In this study 34 premature infants with severe pulmonary dysplasia were studied. They were divided into a control group, which was not given any diuretic, and a treatment group, which received hydrochlorothiazide and spironolactone therapy for eight weeks. The group of infants who received long-term diuretic therapy showed a significantly higher survival rate (84 percent, versus 47 percent). The authors speculate that decreasing the fluid in the lungs, slowed down the development of scar tissue and permanent lung damage. There was no significant difference between the two groups in either total hospital stay, or in the number of days the infants needed to be on ventilators. The authors concluded that combination diuretic therapy can improve respiratory function while decreasing lung damage and increasing survival rates among patients with bronchopulmonary dysplasia. The side effects of this combination of diuretics were not too severe, permitting them to be used for relatively long-term therapy.

The diuretic drug hydrochlorothiazide may strengthen bones in elderly people, according to a study of 309 elderly people. Bones become less dense as people age, increasing the risk of fractures.

Background: Chronic hypercalciuria can contribute to osteoporosis, particularly in men. Objective: To ascertain the effects of resolution of hypercalciuria on bone mineral density. Design: Case series. Setting: Referral service for metabolic bone disease in a tertiary-care teaching hospital. Patients: Five male patients (42 to 66 years of age) with hypercalciuria and osteoporosis. Intervention: Hydrochlorothiazide, 25 mg twice daily, for a mean ([+ or -] SD) of 7.8 [+ or -] 3.6 months. Measurements: Fasting urinary calcium:creatinine ratio, serum calciotropic hormone levels, and bone mineral density before and after hydrochlorothiazide administration. Results: Hydrochlorothiazide resolved hypercalciuria and increased bone mineral density at a rate of 8% and 3% per year at the spine and hip, respectively. Conclusions: Hydrochlorothiazide treatment in hypercalciuric and osteoporotic men was associated with a rapid rebound increase in bone mineral density., Hydrochlorothiazide may effectively increase bone mineral density and correct hypercalciuria and osteoporosis in men. Hypercalciuria is the excessive loss of calcium in the urine, which can lead to brittle bone disease. Researchers treated five patients with the diuretic drug hydrochlorothiazide. Bone mineral density increased 3-8% per year during treatment, and the loss of calcium was arrested.