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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to evaluate the safety and efficacy of indapamide 1.25 mg once daily as monotherapy in elderly patients (65 years and older) with mild to moderate essential hypertension. Two hundred and seventy-nine (279) elderly patients were enrolled in a washout period, during which patients received single-blind placebo for 4 weeks. Patients demonstrating supine diastolic pressures between 95 mm Hg and 114 mm Hg at the end of the 4-week placebo washout period were entered into the 8-week double-blind treatment period. Two hundred and four (204) patients qualified for the study and were randomized to the double-blind treatment; 103 patients received indapamide 1.25 mg and 101 patients received placebo for 8 weeks. Overall, 177 patients (92 indapamide and 85 placebo) completed the study. The primary efficacy criterion was the mean change in supine diastolic blood pressure (DBP) from double-blind baseline to the end of 8 weeks of therapy. By week 8 of the double-blind treatment period, indapamide 1.25 mg produced a statistically significant (P = 0.0037) decrease in supine DBP of 8.2 mm Hg compared to a decrease of 5.3 mm Hg produced in the placebo group. Additionally, indapamide 1.25 mg was statistically (P = 0.0028) more effective than placebo in reducing supine systolic BP (SBP) (-10.1 vs -4.2 mm Hg). The incidence of drug-related adverse events during the double-blind treatment period was similar between the two treatment groups. A low dose of indapamide, 1.25 mg, given once daily for 8 weeks was effective as monotherapy with respect to BP reduction in an elderly population with mild to moderate hypertension. Indapamide 1.25 mg was safe and generally well tolerated in this elderly patient population.
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PMID:Evaluation of indapamide 1.25 mg once daily in elderly patients with mild to moderate hypertension. 918 29

Clinical and epidemiological studies suggest that thiazide diuretics can prevent bone loss and decrease the incidence of hip fractures. However, the mechanism of the effect of diuretics on bone is not clearly established. Indapamide (IDP), a sulfonamide diuretic related to thiazides, is used to treat hypertension. Sixty spontaneously hypertensive rats (SHRs) were divided into four groups and treated with or without IDP (1.5 mg/kg/day) during 8 weeks in the presence or absence of a high sodium load (8% NaCl supplementation in the diet). Sodium and calcium excretions were increased in the rats receiving the high sodium load (SHR + 8% NaCl) comparatively with control rats (SHR). IDP decreased and increased, respectively, calcium and sodium excretions. Serum parathyroid hormone (PTH) was unchanged in any group. Bone density was measured at the femur, tibia, and vertebrae, and bone morphometry was performed at the metaphysis of the femur to evaluate bone architecture. Rats fed a high sodium diet had an average 5.5% decreased bone density at every site except the femoral diaphysis. The trabecular bone volume was also decreased (SHR + 8% NaCl vs. SHR, 11.99+/-0.78 vs. 17.51+/-1.5%, p < 0.05). An increase in trabecular separation suggested that these changes were due to increased bone resorption. In the SHR + 8% NaCl + IDP group, IDP increased bone density and trabecular bone volume (SHR + 8% NaCl + IDP vs. SHR + 8% NaCl, 16.52+/-1.04 vs. 11.99+/-0.78%, p < 0.05). Trabecular separation and pyridinoline/creatinine excretion (SHR + 8% NaCl + IDP vs. SHR + 8% NaCl, 136.39+/-9.62 vs. 195.18+/-22.34 nmol/mmol, p < 0.05) were also decreased by IDP. These results show that in rats receiving a high sodium diet, IDP can reverse sodium-induced bone loss and increased bone resorption independently of changes in serum PTH.
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PMID:The diuretic indapamide increases bone mass and decreases bone resorption in spontaneously hypertensive rats supplemented with sodium. 973 17

Indapamide is a thiazide-related diuretic drug with antihypertensive properties. Its blood pressure-lowering action has been repeatedly demonstrated in acute as well as chronic conditions in various genetically and nongenetically determined forms of hypertension. In rats, the maximally effective oral dose is 3 mg/kg/24 h. The natriuretic effect of indapamide peaked at 3-fold at a dose of 1 mg/kg. In accordance with its antihypertensive properties, indapamide was shown to have excellent efficacy in protecting against target organ damage (heart, kidneys, brain). In addition to its natriuretic effect, it has been shown in several experiments that indapamide lowers the response to sympathetic nerve stimulation, exhibits calcium antagonist properties, enhances the production of prostacyclin, and limits the production of free radicals and of endothelium-dependent vasoconstrictor substances. These effects, even though they are observed at high indapamide concentrations and in a possibly species-dependent manner, may contribute to the beneficial properties of indapamide. The most recent data suggest that low doses of indapamide exert synergistic effects in combination with other antihypertensive drugs such as ACE inhibitors, the effects of which are influenced by the sodium status of the organism.
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PMID:Pharmacological properties of indapamide. Rationale for use in hypertension. 1049 28

Recent international guidelines on the detection, clinical assessment and management of patients with hypertension have highlighted a number of themes that should be incorporated into routine clinical practice. First, although antihypertensive therapy is having a major impact on reducing the incidence of coronary heart disease, cerebrovascular disease and heart failure, community surveys show that most hypertensive patients remain untreated or have suboptimal blood pressure control. Second, the guidelines have emphasised the importance of making an overall assessment of individual patients to gauge their absolute risk of a cardiovascular event; risk factors include not only blood pressure but also target organ damage, the presence of coexisting symptomatic vascular disease and the number of associated cardiovascular risk factors. Patients at the highest risk, especially those with diabetes, the elderly and patients with target organ damage, merit vigorous antihypertensive therapy, and such patients often require treatment with more than one drug to achieve target levels of blood pressure (< 135/80 mm Hg). An additional important theme in recent guidelines has been a move towards using lower dosages and therapies that provide 24-hour blood pressure control with once-daily administration. Since diuretics have been reaffirmed as evidence-based first-line therapy in a broad spectrum of patients with hypertension, especially the elderly, a new lower dosage sustained release formulation of indapamide has been developed (indapamide SR 1.5 mg). Recent multicentre European clinical trials have defined the efficacy and tolerability of indapamide SR 1.5 mg, both relative to other antihypertensive drugs and in key subgroups of patients. Indapamide SR 1.5 mg has an antihypertensive effect, maintained throughout the 24-hour administration interval, equivalent to that of immediate release indapamide 2.5 mg, but the new formulation has even less effect on circulating K+ levels. Indapamide SR 1.5 mg is at least as effective as amlodipine or hydrochlorothiazide. In patients with left ventricular hypertrophy (LVH), a comparative study of indapamide SR 1.5 mg and enalapril (the LIVE study) used a rigorous unique study design with blinded reading of echocardiograms to show that after 1 year the ACE inhibitor had no significant effect on LVH regression, whereas indapamide SR 1.5 mg produced significant reductions in left ventricular mass index. Diuretic-based therapy for hypertension has been reaffirmed in international guidelines as effective first-line therapy, especially in the elderly and patients with LVH. Indapamide SR 1.5 mg shows an improved efficacy-tolerability profile, with impressive 24-hour effects on blood pressure, important ancillary properties with regard to LVH and cardiovascular protection.
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PMID:Clinical implications of indapamide sustained release 1.5 mg in hypertension. 1049 30

Diuretics and beta-blockers are the only antihypertensives known for their significant reduction of cardiovascular morbidity and mortality, particularly in the elderly. The use of low-dose diuretics can improve the efficacy-safety ratio. Hypokalemia, hypomagnesemia as well as disturbances of carbohydrate and lipid metabolism are dose-dependent side effects of diuretics but only minimal during the low-dose therapy. A novel low-dose formulation of indapamide was developed as a sustained-release (SR) coated tablet (1.5 mg/day) and compared to the immediate release (IR) formulation of indapamide (2.5 mg/day). A > 50% reduction in the number of patients with serum potassium levels < 3.4 mmol/l among hypertensive patients treated with indapamide SR as compared to IR was observed. Indapamide SR has also been shown to be effective (more than 20 mg enalapril) in the reduction of left ventricular mass index (LVMI) in hypertensive patients treated for one year (LIVE study). Therefore, low-dose diuretics are, in accordance with international recommendations for the low-dose antihypertensive drugs, a first line therapy of hypertension.
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PMID:[Renaissance of diuretics in the treatment of hypertension]. 1059 55

Left ventricular hypertrophy (LVH) is now recognized as a major risk factor for cardiac morbidity and mortality, a component of which is independent of associated coronary heart disease. The mechanisms that underlie this risk are increasingly understood and include disturbances in cardiac electrophysiology, coronary perfusion and myocardial contractile function. Recognition that regression of LVH confers prognostic benefit has focused attention on developing optimal treatments to achieve this. Early studies suggested that regression is achievable using a variety of antihypertensive classes. Many of these early studies were either poorly controlled or of inadequate size to provide reliable comparisons between different agents. Subsequently a number of meta-analyses, based on selections of these early studies, have been published. More recently, a number of well-designed prospective clinical trials have been published or are under way. In summary of these results: (1) the extent of regression seen in early studies appears to be greater than that reported in recent large, well-designed trials, possibly due to regression to the mean in small studies with high coefficients of variation for echocardiographically measured left ventricular (LV) mass index; (2) meta-analyses based on these early studies tend to suggest that angiotensin-converting enzyme (ACE) inhibitors may be most effective in regressing LVH; (3) recent larger trials [Treatment Of Mild Hypertension Study (TOMHS), the Veterans Administration (VA) study, and Left ventricular hypertrophy: Indapamide Versus Enalapril (LIVE)] indicate that angiotensin-converting enzyme inhibitors and diuretics maintain a strong place in achieving regression of LVH. Long-term studies currently under way should help clarify the prognostic benefit associated with regression of LVH using antihypertensive therapy. Future work will focus on whether regression of LV mass is associated with reversal of the underlying pathophysiology of hypertrophy and, ultimately, whether prevention of LVH should be the optimal goal.
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PMID:Regression of left ventricular hypertrophy: do antihypertensive classes differ? 1095 84

The development of hypertension is accompanied by rarefaction of arterioles and capillaries in both animal models and humans. Although many studies have examined the effects of antihypertensive therapies on hemodynamics, cardiac hypertrophy, and large vessel structure, the question of whether changes in microvascular density induced by hypertension can be restored by pharmacologic treatment has yet to be answered. We report a series of experiments performed in rats with renovascular hypertension induced by unilateral nephrectomy and renal artery stenosis (Goldblatt one-kidney, one-clip model). Animals were treated for 4 weeks, after renal artery clipping, either with an angiotensin converting enzyme inhibitor (perindopril [PER], 0.76 mg/kg/day), or with an indol derivative diuretic with specific vascular properties (indapamide [IDP], 0.24 mg/kg/day) or with the combination of both drugs at the same doses as during monotherapy. Coronary microvessel densities (arterioles and capillaries) were evaluated by double immunolabeling in nonserial cryostat sections of the left ventricular inner myocardium. After 4 weeks of hypertension (mean arterial pressure, 174+/-11 v 124+/-5 mm Hg in normotensive (NT) controls, P < .01), cardiac hypertrophy (+59%, P < .001) was associated with a significant increase in myocardial arteriolar density (+27%, P < .01), and a decrease in capillary density (-12%, P < .05). Treatment with PER prevented the increase in arterial pressure, heart weight, and arteriolar density, but did not significantly affect the low coronary capillary density in comparison with that measured in untreated hypertensive (HT) rats. Treatment with IDP preserved normal capillary myocardial density but did not significantly lower the blood pressure (BP) (169+/-9 mm Hg) and only slightly reduced the cardiac ventricular hypertrophy: - 14% v untreated HT (P < .05) and +37% v NT (P < .01). In the same way, IDP normalized the left ventricular capillary density in spontaneously HT rats (+18% v untreated rats, P < .01). The combination of both drugs, PER and IDP, at the same low doses as during monotherapy, resulted in normal levels of arterial pressure and complete normalization of cardiac hypertrophy and arteriolar and capillary myocardial densities. In conclusion, the results observed after PER suggest that blockade of the renin-angiotensin system could inhibit large coronary vessel growth but minimally affects the capillary density despite complete normalization of BP. Indapamide could have beneficial effect on myocardial capillary density. The combination of IDP and PER has additional effects and prevents the increase in BP and cardiac weight, and reverses microvascular rarefaction, specifically arteriolar and capillary densities.
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PMID:Coronary microvasculature alteration in hypertensive rats. Effect of treatment with a diuretic and an ACE inhibitor. 1120 83

This study was designed to examine changes of hemorheological parameters in essential arterial hypertension subjects following antihypertensive drug therapy. Eighty two female subjects were enrolled, and sub-divided into two groups based upon their high shear whole blood viscosity being lower (L) or higher (H) than normal controls. Equal numbers of L and H subjects were then treated for four weeks with one of four agents: angiotensin-converting enzyme inhibitor (ACE-inhibitor, Spirapril - 6 mg/day); calcium antagonist (Isradipin - 5 mg/day); beta-1-blocker (Talinolol - 100 mg/day); diuretic (Indapamide - 1.5 mg/day). Both prior to and following drug treatment for six weeks, hemorheological measurements included plasma viscosity; high and low shear whole blood viscosity, hematocrit, fibrinogen and RBC aggregation. Treatment with each of the four drugs significantly (p<0.05) reduced blood pressure in both the L and H groups. However, the hemorheological effects of antihypertensive drug therapy differed markedly between groups: plasma and whole blood viscosity were significantly elevated in the L groups whereas these parameters were significantly decreased in the H groups. Fibrinogen levels and RBC aggregation decreased in both groups, whereas hematocrit was unaffected. These results thus suggest that the rheologic effects of antihypertensive drug therapy depend strongly on the initial, pre-treatment status of the subject, and that for some subjects, such therapy can result in adverse hemorheological alterations.
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PMID:Effects of antihypertensive therapy on hemorheological profiles in female hypertensive patients with initially low or high whole blood viscosity. 1208 61

A 60-year-old woman who had been successfully treated with atenolol and cardiac pacing for hypertension and long QT syndrome developed recurrent episodes of palpitations and syncope. Several days prior to these episodes, indapamide 2.5 mg/day was taken for better control of hypertension. The episodes were associated with prolongation of QT interval and mild hypokalemia (3.1 MEQ/L). Indapamide was immediately stopped, but the QT remained prolonged 2 days later, although the potassium level was normalized. This case suggests that indapamide can cause potassium independent prolongation of the QT interval, resulting in arrhythmia induced syncope.
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PMID:Indapamide induced syncope in a patient with long QT syndrome. 1238 Jul 80

Although recent trials have shown that antihypertensive treatment can bring about a reduction in stroke, coronary heart disease, heart failure and renal disease, the situation is no longer improving. This is due to the fact that the percentage of hypertensive patients with satisfactory blood pressure is still very poor. International guidelines on hypertension indicate the importance of assessing the absolute risk of patients and the use of a lower dose of drugs to improve the efficacy-tolerability profile. Diuretics used at lower dosage than in the past are effective in reducing morbidity and mortality and continue to be drugs of first choice in the treatment of hypertension. Indapamide sustained release (Natrilix SR) 1.5 mg has an antihypertensive effect equivalent to indapamide immediate release 2.5 mg with a 50% reduction in incidence of serum potassium levels <3.4 mmol/l. Natrilix SR has proved to have a neutral effect both on lipid and glucose profiles and to reduce microalbuminuria in diabetic hypertensive patients. Recent multicentre European clinical trials have shown that Natrilix SR decreases diastolic blood pressure to <90 mmHg in about 75% of patients treated for 1 year. In elderly patients with isolated systolic hypertension, Natrilix SR has been proven to be as effective as amlodipine 5 mg and significantly more effective than hydrochlorothiazide 25 mg. Natrilix SR produces regression of left ventricular hypertrophy which, in the Left ventricular hypertrophy: Indapamide Versus Enalapril study was greater than that induced by enalapril. Natrilix SR represents an appropriate choice not only as a first-line drug in many hypertensive patients but also in at-risk patients like the elderly, subjects with other cardiovascular risk factors, target organ damage, diabetes, or impaired renal function.
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PMID:Clinical role of Natrilix SR in the treatment of at-risk hypertensive patients. 1276 62


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