Dose response to chlorthalidone in patients with mild hypertension; Efficacy of a lower dose

Materson, Barry J.; Oster, James R.; Michael, Ulrich F.; Bolton, Sanford; Burton, Zeb C.; Stambaugh, John E.; Morledge, John H.

doi:10.1002/cpt1978242192

Cited by 104 publications

(27 citation statements)

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“…This dissociation between the diuretic dose-response curves for blood pressure reduction and those for serum potassium and uric acid levels, for example, is now well known. 25 In this study, however, there were no observed differences in subjective side effects between the two dose groups.…”

Section: -21contrasting

confidence: 56%

Treatment of hypertension in the elderly: I. Blood pressure and clinical changes. Results of a Department of Veterans Affairs Cooperative Study.

et al. 1990

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We compared the efficacy and adverse effects of antihypertensive drug regimens in 690 men past age 60 with diastolic blood pressure 90-114 mm Hg and systolic blood pressure less than 240 mm Hg. They received either a low (25-50 mg) or high (50-100 mg) dose of hydrochlorothiazide daily. Of 644 patients who completed the hydrochlorothiazide titration, 375 (58.2%) were responders (diastolic blood pressure <90 and <5 mm Hg below baseline) and 92.8% of these completed a 6-month maintenance period. Blood pressure was reduced from 157.6/98.5 mm Hg by 18.3/9.5 mm Hg with low dose hydrochlorothiazide and by 20.4/9.6 mm Hg with high dose hydrochlorothiazide; more patients achieved goal blood pressure with the high dose. Whites and blacks responded equally. Serum potassium less than 3.5 mmol/1 occurred in 104 of 321 (32.3%) of the high dose versus 62 of 333 (18.6%) of the low dose hydrochlorothiazide patients. The 269 nonresponders to hydrochlorothiazide were randomly assigned in a double-blind study to receive hydralazine, methyldopa, metoprolol, or reserpine in addition to hydrochlorothiazide; 79.2% responded to the addition of the second drug and 87.3% of these completed a 6-month maintenance phase. Overall, there were no significant efficacy differences among the step 2 regimens. We conclude that the lower dose of hydrochlorothiazide was nearly as effective as the higher dose, and the addition of a second drug was effective and generally well tolerated in elderly patients. strate improvement in previously demonstrated behavioral deficits in young men and women after long-term antihypertensive therapy.This study was designed to evaluate the effect of various antihypertensive regimens on blood pressure, biochemical values, symptomatology, and cognitive and behavioral function in an elderly hypertensive population. We performed a double-blind, randomized, multicenter trial that included detailed psychometric testing. The objective of the psychometric testing was to assess the effects of various blood pressure-lowering regimens on memory, motor skills, and other cognitive functions, activities of daily living, and mood for those patients whose blood pressure was controlled. We wanted to determine both the antihypertensive efficacy and comparative adverse effects of 50 mg hydrochlorothiazide (HCTZ) daily compared with 100 mg daily and, in those patients who were nonresponsive to the diuretic, the comparative efficacy and adverse effects

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Section: -21contrasting

confidence: 56%

Treatment of hypertension in the elderly: I. Blood pressure and clinical changes. Results of a Department of Veterans Affairs Cooperative Study.

et al. 1990

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“…Diuretic-related reductions in serum K ϩ are typically dose related and usually range from 0.2 to 0.6 mmol/L. [11][12][13][14][37][38][39][40][41] This well-described relationship is depicted by arrow "A" in Figure 1. A recent meta-analysis of 59 studies involving 83 thiazide diuretic treatment arms found a significant correlation between the degree of diuretic-induced hypokalemia and the increase in plasma glucose, and there was evidence that prevention of hypokalemia with K ϩ supplementation or potassium-sparing agents lessened the degree to which plasma glucose increased consequent to diuretic therapy.…”

Section: Possible Relationship To Hypokalemiamentioning

confidence: 99%

Thiazide-Induced Dysglycemia

et al. 2008

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“…Data obtained with chlorthalidone so far indicate that the plateau of the dose-response antihypertensive curve is reached with a daily dose of 25 mg and that increasing the dosage does not increase the BP-lowering effect but further increases the occurrence of negative metabolic effects, principally hypokalemia (10,11). Data obtained with hydrochlorothiazide, the most widely used thiazide diuretic in clinical practice, are less certain and suggest that the plateau of the dose-response BP-lowering curve is reached with the dose of 50 mg/d, whereas negative metabolic effects, principally hypokalemia, occur in a dosedependent manner with a dose up to 100 mg/d (9,12).…”

Section: Choice Of Optimal Dosementioning

confidence: 99%

Thiazide Diuretics in the Treatment of Hypertension

Salvetti¹,

Ghiadoni²

2006

Journal of the American Society of Nephrology

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Thiazide diuretics were the first tolerated efficient antihypertensive drugs that significantly reduced cardiovascular morbidity and mortality in placebo-controlled clinical studies. Although these drugs today still are considered a fundamental therapeutic tool for the treatment of hypertensive patients, the following considerations should be taken into account. Although there are some indications that chlorthalidone can offer additional advantages as compared with other compounds, a recent metaanalysis of placebo-controlled trials suggested that the beneficial effects of thiazide diuretics could be a class effect. Thiazide diuretics must be used at appropriate and/or optimal doses to achieve the optimal antihypertensive effect with the smallest occurrence of side effects, including alterations in glucose and lipid profiles and hypokalemia. Moreover, because thiazide diuretics can increase the incidence of new-onset diabetes, especially when combined with ␤ blockers, caution is advised in using these drugs above all in patients who are at high risk for developing diabetes, in whom thiazide diuretics should be used at the lowest active dose and possibly in combination with drugs that block the renin-angiotensin system. Finally, the current debate on whether thiazide diuretics are the first-choice drug for most patients with uncomplicated hypertension, as stated in the Seventh Joint National Committee Report, or are included in the major classes of antihypertensive agents that are suitable for initiation and maintenance of therapy, as reported in the European Society of Hypertension-European Society of Cardiology Guidelines, derives from different interpretations of controlled clinical trial data on drug class comparison and of cost-benefit analyses. However, considering that the benefit of antihypertensive drugs seems to be due principally to BP lowering per se without definitive evidence of the superiority of a particular drug class and that there is no cost-benefit analysis showing the superiority of thiazide diuretics, it is believed that these drugs should not be considered as the only first-choice drug but included among first-choice drugs.

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Dose response to chlorthalidone in patients with mild hypertension; Efficacy of a lower dose

Cited by 104 publications

References 1 publication

Treatment of hypertension in the elderly: I. Blood pressure and clinical changes. Results of a Department of Veterans Affairs Cooperative Study.

Treatment of hypertension in the elderly: I. Blood pressure and clinical changes. Results of a Department of Veterans Affairs Cooperative Study.

Thiazide-Induced Dysglycemia

Thiazide Diuretics in the Treatment of Hypertension

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