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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Oslo Hypertension Study began in 1972; patients were followed for an average of 66 months (range: 60 to 78). A total of 785 healthy men, aged 40 to 49, with mild hypertension was randomly assigned to either a drug-treated group or to an untreated control group. Hydrochlorothiazide was used alone in 36 percent of patients, in combination with propranolol in 26 percent, and with methyldopa in 20 percent. Other drugs, including combinations with hydrochlorothiazide, were used in 18 percent. A total of 95 percent of patients in the drug-treated group received hydrochlorothiazide. Complications of hypertension such as stroke and aneurysm occurred only in the control group. Coronary events were more numerous in the drug-treated group; thus, the total incidence of cardiovascular complications did not significantly differ between the treated and untreated groups. After five and 10 years, total mortality was the same in both groups. However, the coronary heart disease mortality rate at 10 years was significantly greater in the drug-treated group than in the untreated control group (14 versus three, p less than 0.01). This article presents possible reasons for the failure of antihypertensive drug therapy to prevent coronary heart disease. The adverse effect of diuretics and beta-adrenergic blockers, both on lipid and carbohydrate metabolism, is contrasted with the effect of the alpha-adrenergic blocker prazosin, which has been shown to have no adverse effect on the blood lipid profile. In a short-term trial that was part of the Oslo Study, prazosin was found to reduce total serum cholesterol by 9 percent, low-density lipoprotein and very-low-density lipoprotein cholesterol by 10 percent, and total triglycerides by 16 percent. All these changes are statistically significant.
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PMID:Coronary heart disease and treatment of hypertension. Some Oslo Study data. 286 57

Blood pressure, cardiac output, plasma volume, renin, and aldosterone were measured in 13 patients with essential hypertension on placebo and after 1, 4, and 12 wk on hydrochlorothiazide 100 mg daily. In 9 patients the same variables were also measured after 24 and 36 wk. Hydrochlorothiazide lowered mean arterial pressure (p less than 0.01). Cardiac output was reduced after 4 and 12 wk of treatment, followed by a return to placebo levels. Stroke volume changed in the same way but heart rate and total peripheral resistance did not differ from placebo values. Plasma volume was reduced after 1 and 24 wk. Renin was permanently elevated (p less than 0.01), but aldosterone rose only during the first 12 wk of treatment. A comparison between responders (greater than 10% fall in mean arterial pressure) and nonresponders (less than 10% fall) revealed different hemodynamic patterns. In responders the initial fall in cardiac output was followed by a return to pretreatment levels, whereas in nonresponders it was permanently reduced. Consequently, total peripheral resistance was lowered only in responders. Nonresponders tended to show a greater degree of plasma volume depletion and greater stimulation of renin and aldosterone, which probably contributed to elevated peripheral resistance. It is concluded that changes in cardiac output are unlikely to be of decisive importance in the ultimate reduction of peripheral resistance in responders to thiazide therapy.
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PMID:Hemodynamic changes during long-term thiazide treatment of essential hypertension in responders and nonresponders. 698 24

The effect of hydrochlorothiazide (1 mg/kg per day) on left ventricular (LV) mass and systolic and diastolic function was investigated in two-kidney, one clip (2K1C) renovascular hypertensive rats. Hydrochlorothiazide was administered from 8 weeks, and LV mass and function were measured at 16 weeks after surgery to induce hypertension. Cardiac performance was determined from cardiac output, stroke volume (per 100 g of body weight), and stroke work (per gram of LV weight) versus LV end-diastolic pressure (LVEDP) and versus LV strain relations in anesthetized open-chest, ventilated rats. LV compliance was determined from the LVEDP versus strain relation. Strain was calculated from LV end-diastolic short-axis diameter values. Hydrochlorothiazide reduced systolic blood pressure in 2K1C rats to levels similar to those in sham-operated controls (sham) at 12 weeks after surgery. A reduced afterload failed to influence LV mass, as left LV hypertrophy developed to the same extent in treated 2K1C rats. 2K1C hypertension produced abnormal cardiac performance with altered cardiac output, stroke volume, and stroke work versus LVEDP relations (stroke work versus LVEDP, intercept of 2K1C versus sham, p < 0.001). This was attributed to a decreased ventricular compliance (strain versus LVEDP, slope of 2K1C versus sham, p < 0.001). In contrast, hydrochlorothiazide improved ventricular compliance (strain versus LVEDP, slope of 2K1C versus 2K1C hydrochlorothiazide, p < 0.01) and thus returned the stroke work versus LVEDP relation to sham values (intercept of 2K1C versus 2K1C hydrochlorothiazide, p < 0.001). We conclude that hydrochlorothiazide reduces blood pressure but not the development of ventricular hypertrophy in 2K1C rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hydrochlorothiazide improves ventricular compliance and thus performance without reducing hypertrophy in renal artery stenosis in rats. 768 25

Lowering elevated blood pressure (BP) with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient's BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC) emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective) adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT) is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.
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PMID:Metoprolol succinate extended release/hydrochlorothiazide combination tablets. 1770 35

Hydrochlorothiazide (HCTZ) has become by far the most commonly prescribed antihypertensive drug in the US. In 2008, 47.8 million prescriptions were written for HCTZ alone and 87.1 million prescriptions for HCTZ combinations. However, there is no evidence that HCTZ in its usual dose of 12.5-25 mg daily reduces myocardial infarction, stroke, or death. In a meta-analysis of 19 randomized trials with over 1400 patients, the 24-hour decrease in blood pressure with HCTZ was inferior to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and calcium channel blockers (P <.001 for all). Even in combination with an angiotensin-converting enzyme inhibitor, HCTZ was found to reduce morbidity and mortality less well than a calcium channel blocker. As measured by the adherence rate, thiazides are less well tolerated than any other drug class. Because outcome data at the usual daily dose of 12.5-25 mg are lacking, antihypertensive efficacy is paltry, and adherence is poor, HCTZ is an inappropriate first-line drug in hypertension. If a "thiazide-type" diuretic is indicated, either chlorthalidone or indapamide should be selected.
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PMID:Half a century of hydrochlorothiazide: facts, fads, fiction, and follies. 2262 91

We concluded in 2004 that the first-choice treatment for hypertension in adults was single-agent therapy with the thiazide diuretic chlortalidone or, when this drug is not available, the thiazide diuretic hydrochlorothiazide. As of early 2014, does evidence challenge this choice in adults without diabetes or cardiovascular or renal disease? To answer this question, we reviewed the available evidence, using the standard Prescrire methodology. The current treatment threshold for hypertensive adults without diabetes or cardiovascular or renal disease is blood pressure above 160/100 mmHg or 160/90 mmHg, with some uncertainty over which diastolic threshold should be used. Apart from certain diuretic-based combinations, the use of combinations of antihypertensive drugs as first-line therapy has not been evaluated in terms of the complications of hypertension. A number of systematic reviews with meta-analyses of data on tens of thousands of patients have compared the main classes of antihypertensive drugs against each other and against placebo. Compared with placebo, only low-dose thiazide diuretics and angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce all-cause mortality in hypertensive patients. They prevented about 2 to 3 deaths and 2 strokes per 100 patients treated for 4 to 5 years. Several systematic reviews concluded that neither calcium-channel blockers, ACE inhibitors nor beta-blockers are more effective than thiazide diuretics in reducing mortality or the incidence of stroke. The efficacy of the thiazide diuretic chlortalidone is supported by the highest-level evidence, from three comparative clinical trials versus placebo, an ACE inhibitor, or a calcium-channel blocker, in more than 50 000 patients. In one of these trials, chlortalidone was superior to the ACE inhibitor lisinoprilin preventing stroke. It was also superior to the calcium-channel blocker amlodipine in preventing heart failure. The effect of hydrochlorothiazide, combined with amiloride or triamterene, on cardiovascular morbidity and mortality has been demonstrated in three comparative clinical trials versus placebo, a beta-blocker, or a calcium-channel blocker. Hydrochlorothiazide appeared more effective than the beta-blocker atenolol in reducing the incidence of coronary events. The addition of a potassium-sparing diuretic (amiloride or triamterene) to first-line hydrochlorothiazide therapy has not been demonstrated to provide clinical benefit. The evaluation of indapamide, another thiazide diuretic, is less convincing. Since no head-to-head trials have been conducted, there is no evidence that it is more effective than chlortalidone or hydrochlorothiazide. None of the antihypertensive drugs appears to have a better overall adverse effect profile than the others. Thiazide diuretics can provoke hyperglycaemia and diabetes, although this does not reduce their efficacy in the prevention of cardiovascular events. As of early 2014, the first-choice treatment for hypertension in nondiabetic adults without cardiovascular or renal disease should be chlortalidone. If chlortalidone is not available, it appears reasonable to choose another thiazide diuretic, hydrochlorothiazide, possibly combined with amiloride or triamterene. When a diuretic cannot be used, it is better to choose an ACE inhibitor: captopril, lisinopril or ramipril.
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PMID:Treating essential hypertension. The first choice is usually a thiazide diuretic. 2532 25

Diuretics have been used for years to treat hypertension as both a monotherapy and in combination. Hydrochlorothiazide, indapamide, and chlorthalidone have frequently been considered in the same category as thiazide diuretics, but there is no evidence that their activities are similar. Studies have shown that chlorthalidone and indapamide reduce cardiovascular morbidity and mortality; however, there is no study indicating that hydrochlorothiazide has beneficial effects on cardiovascular outcomes such as myocardial infarction, renal failure, stroke, or death. Hydrochlorothiazide has less effect on blood pressure, a high risk of metabolic side effects, and may not have pleiotropic effects. As a result, it is not accurate to evaluate chlorthalidone and indapamide as similar to thiazide diuretics. Indapamide or chlorthalidone is a better choice of diuretic for use in the treatment of hypertension.
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PMID:[All diuretics used in the treatment of hypertension are not the same]. 2810 27