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PubMed2004

Cardiovascular outcomes using doxazosin vs. chlorthalidone for the treatment of hypertension in older adults with and without glucose disorders: a report from the ALLHAT study.

Insulin resistance underlies most glucose disorders in adults and is associated with an increased risk of cardiovascular disease. Alpha blockers decrease insulin resistance, whereas diuretics increase insulin resistance. The authors studied the effects of these two classes of hypertension medications (doxazosin, an a blocker, and chlorthalidone, a diuretic) on cardiovascular disease outcomes in adults aged >55 years with hypertension and glucose disorders who were participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (8749 had known diabetes mellitus and 1690 had a newly diagnosed glucose disorder [fasting glucose >/=110 mg/dL]). There was no difference in either group between the chlorthalidone- and doxazosin-based treatments with regard to fatal or nonfatal myocardial infarction or all-cause mortality. There was, however, a difference for combined cardiovascular disease (myocardial infarction, revascularization procedures, angina, stroke, heart failure, and peripheral arterial disease) in favor of the diuretic. This difference was due primarily to an increased heart failure risk in those treated with doxazosin (relative risk, 1.85; 95% confidence interval, 1.56-2.19) in the known diabetes mellitus group and a relative risk of 1.63 (95% confidence interval, 1.05-2.55) in those with a newly diagnosed glucose disorder despite lower glucose levels on follow-up in those treated with a blockers. The authors conclude that treatment of hypertension with doxazosin in adults with glucose disorders incurs the same risk of coronary heart disease as treatment with chlorthalidone; however, treatment with doxazosin increases the risk of combined cardiovascular disease and heart failure despite lower glucose levels.

Aged↗

PubMed1983

Effect on intra-arterial blood pressure of slow release metoprolol combined with placebo or chlorthalidone.

Thirty patients with essential hypertension participated in a double blind crossover trial in which they were randomly allocated to treatment with either once daily slow release metoprolol (200 mg) with placebo or once daily slow release metoprolol (200 mg) with chlorthalidone (25 mg). Ambulatory intra-arterial blood pressure was recorded continuously for 24-48 hours before treatment and two months after each change in regimen. The response of blood pressure and pulse rate to a standard exercise protocol that included supine rest and tilt, isometric, and dynamic bicycle exercise was measured during the same recording periods. Both treatments appreciably reduced blood pressure and pulse rate; mean daytime intra-arterial blood pressure was reduced from 174/95 mm Hg to 158/85 mm Hg by metoprolol plus placebo and to 143/78 mm Hg by metoprolol plus chlorthalidone. This reduction with the combined treatment was significantly greater than with metoprolol and placebo (p systolic = 0.001, p diastolic = 0.004). Mean night time pressures were reduced from 148/78 mm Hg to 139/75 mm Hg by metoprolol plus placebo and to 116/61 mm Hg by metoprolol plus chlorthalidone. Again the reduction in blood pressure was significantly greater with combined treatment (p less than 0.001) than with metoprolol plus placebo. Once daily slow release metoprolol is effective in controlling blood pressure, but this effect is greatly enhanced by the addition of a diuretic.

Adult↗

PubMed1983

Total body potassium in patients receiving chlorthalidone and metoprolol for hypertension.

Measurements of potassium status were reviewed in 23 hypertensive patients receiving metoprolol either alone or in combination with chlorthalidone or chlorthalidone plus potassium over an average period of nine months. There was no statistically significant change in plasma potassium, total blood cell or total body potassium in patients on long-term metoprolol. Four subjects (17%) in the diuretic groups developed hypokalaemia (serum potassium less than 3.0 mmol/l) in the absence of significant falls in total blood cell or total body potassium. Thus the use of chlorthalidone plus potassium did not provide adequate prophylaxis against hypokalaemia even in metoprolol recipients. The study confirms that monitoring parameters of potassium handling is still necessary in beta-blocker recipients who also receive diuretics alone or in a fixed-dose combination with potassium.

Adult↗

PubMed1984

The efficacy of a potassium-sparing combination of chlorthalidone and triamterene in the control of mild and moderate hypertension. I.

Chlorthalidone 25 mg/triamterene 50 mg in once-daily oral doses was as effective in reducing blood pressure as chlorthalidone 25 mg alone. The decrease in serum potassium was statistically significantly less with the combination than for chlorthalidone. There were no notable differences between the treatments in any other measure of laboratory safety or adverse reactions.

Adult↗

PubMed1984

The efficacy of a potassium-sparing combination of chlorthalidone and triamterene in the control of mild and moderate hypertension. II.

Chlorthalidone 50 mg/triamterene 50 mg in once-daily oral doses was as effective in reducing blood pressure as chlorthalidone 50 mg alone. The decrease in serum potassium was statistically significantly less with the combination than for chlorthalidone. There were no notable differences between the treatments in any other measure of laboratory safety or adverse reaction.

Adult↗

PubMed1985

Atenolol and chlorthalidone in combination in the management of older hypertensive patients: a randomized clinical trial.

In a double-blind, crossover study in 100 elderly hypertensive patients, the hypotensive effect of a fixed combination of atenolol (50 mg) with chlorthalidone (12.5 mg) was compared with that of each of its component drugs given alone. Patients were allocated at random into two groups: one group received treatment for 4 weeks with either the combination or atenolol alone before being crossed over to the alternative medication for a further 4 weeks; the other group received either the combination or chlorthalidone alone and followed the same treatment pattern. Dosage was a single tablet per day given in the morning. Blood pressure and pulse rate were measured approximately 24 hours after dosing at the end of each treatment period. The results showed that significantly lower blood pressures were achieved, both in the standing and lying positions, with the combination than with either atenolol or chlorthalidone used alone. Combination treatment was well tolerated, few side-effects being reported and there was no significant disturbance of plasma electrolytes.

Aged↗

PubMed1996

Double-blind parallel study of a combination of chlorthalidone 50 mg and triamterene 50 mg in patients with mild and moderate hypertension.

In a double-blind, partial cross-over study of 141 patients with mild to moderate hypertension, chlorthalidone 50 mg was compared with chlorthalidone 50 mg/triamterene 50 mg combination treatment. The study assessed clinical efficacy in the reduction of blood pressure, and safety with regard to serum potassium concentration and adverse reactions. Both treatment regimens were found to offer equivalent therapeutic success, but the decrease in serum potassium concentration was significantly less with the combination treatment than with chlorthalidone alone.

Adult↗

PubMedDate not supplied

Long-term treatment with chlorthalidone reduces experimental hydrops but does not prevent the hearing loss.

Long-term treatment of guinea pigs with the diuretics chlorthalidone and acetazolamide, following the experimental obstruction of the endolymphatic duct, was assessed using chronically implanted round window cochlear electrodes. The diuretic chlorthalidone appeared to curb the progressive low-frequency sensitivity loss during the first 4 weeks following surgery, as compared with animals receiving the diuretic acetazolamide or no treatment. However, this apparent beneficial effect decreased after 4 weeks and was not apparent at 14 weeks post-induction. On the other hand, morphological control at the end of 14 weeks confirmed a marked reduction in hydrops in the chlorthalidone-treated animals. The data clearly demonstrate a dissociation between hydrops and the development of hearing loss and suggest that the augmenting endolymph volume is only one of several contributing factors to the deteriorating auditory function in experimental hydrops.

Acetazolamide↗

PubMed1985

Influence of the administration time on the antihypertensive and hypokalaemic effects of chlorthalidone in patients with primary hypertension.

A double-blind crossover study was designed to compare the antihypertensive and hypokalaemic effects of chlorthalidone administered at 10h00 and 22h00 to sixteen patients with primary hypertension. Blood pressure values during chlorthalidone treatment at 10h00 did not differ significantly from those at 22h00. Significant correlation (r = 0.8987) was seen, however, only between the patients' blood pressure during the placebo period and the fall in blood pressure obtained by administration of chlorthalidone at 22h00. The serum potassium level fell significantly (p less than 0.01) during morning treatment while a slight, insignificant fall was found during evening treatment. No correlation was seen between decrease in blood pressure and decrease in serum potassium level.

Adult↗

PubMed1983

Comparison of chlorthalidone and spironolactone in low--renin essential hypertension.

Nineteen patients with uncomplicated essential hypertension and low activity of plasma renin in response to a change from recumbency to an upright posture along with furosemide administration were given spironolactone, 400 mg/d, or chlorthalidone, 100mg/d, in a double-blind, random-sequence, crossover trial. The sequence of treatments was placebo for 2 months, one active drug for 2 months, placebo again for 1 month and the other active drug for 2 months. With both active treatments the average systolic, diastolic and mean arterial pressures decreased significantly. The two agents were equally efficacious in lowering the blood pressure regardless of the severity of hypertension during placebo treatment. Body weight, 24--hour urinary excretion of sodium, the plasma renin activity and the plasma aldosterone level at the end of the initial placebo period did not allow us to predict the response to either drug. Both drugs reduced the body weight and increased the stimulated plasma renin level activity. Chlorthalidone significantly increased the serum uric acid level and significantly reduced the serum potassium level. Three patients experienced orthostatic dizziness during spironolactone therapy, but no adverse symptoms were observed with chlorthalidone therapy. Thus, spironolactone is an effective alternative to thiazide-type drugs in patients with low-renin essential hypertension.

Adult↗

PubMed1984

Propranolol versus chlorthalidone--a prospective therapeutic trial in children with chronic hypertension.

A prospective study of propranolol versus chlorthalidone has been performed in eleven patients with renal hypertension and one with essential hypertension. The patients were treated for 4 to 6 weeks consecutively. Both drugs proved to be effective in lowering elevated systolic and diastolic blood pressure. The mean blood pressure decreased by 22.3 mm Hg in propranolol-treated patients and by 15 mm Hg in chlorthalidone-treated patients. One patient developed an asthmatic attack provoked by propranolol. Four of twelve patients receiving chlorthalidone developed hypokalemia and required potassium supply. Both drugs can be recommended as drugs of first choice in children with hypertension.

Adolescent↗

PubMed1984

Different effects of metoprolol and chlorthalidone on serum lipoprotein levels in mild hypertension. Possible implications for coronary heart disease risk status.

The effects of chlorthalidone and metoprolol on fasting plasma lipids and lipoprotein levels were compared in two similar nonrandomized groups of patients with mild hypertension. Chlorthalidone therapy was associated with an increase in serum cholesterol of 8.1% (17 mg/dl), mainly reflecting an increase in low-density lipoprotein (LDL)-cholesterol. High-density lipoproteins (HDL)-cholesterol decreased, but the difference between pre- and posttreatment levels did not reach statistical significance. Serum triglyceride (TG) concentration increased by 16% (20 mg/dl). Metoprolol therapy was not associated with changes in total, very low-density lipoprotein (VLDL)-, LDL- and HDL-cholesterol levels. Serum TG concentration increased by 22% (28 mg/dl), mainly due to an increase in VLDL-TG. Application of the Israel Ischemic Heart Disease Study data to these findings could predict only a very slight decrease in the 5-year estimated probability of myocardial infarction in the chlorthalidone-treated group. Metoprolol therapy has, theoretically, a more favorable influence on coronary heart disease risk status. These data suggest that the different forms of therapy for mild hypertension have a different effect on the theoretical coronary heart disease risk status, a fact that should be taken into consideration in the choice of medication.

Body Weight↗

PubMed1981

A comparison of chlorthalidone-reserpine and hydrochlorothiazide-methyldopa as step 2 therapy for hypertension.

Two fixed-combination drugs commonly used in the step 2 treatment of hypertension, chlorthalidone plus reserpine and hydrochlorothiazide plus methyldopa, were compared in an evaluation of efficacy and adverse reactions. Ninety-one percent of the chlorthalidone-reserpine group achieved diastolic blood pressures of 90 mmHg or lower compared with 55% of the hydrochlorothiazide-methyldopa group. The incidence of adverse reactions in the chlorthalidone-reserpine group was 31% compared with an incidence of 64% in the hydrochlorothiazide-methyldopa group.

Chlorthalidone↗

PubMed1993

[Hemodynamic effects of low doses of chlorthalidone in patients with mild systemic arterial hypertension].

PURPOSE: To evaluate the hemodynamic effects of low doses of chlorthalidone (CHT) in patients with systemic arterial hypertension (SAH). METHODS: Eight patients with mild SAH, mean age of 52 +/- 8.9 years, 7 men, were studied. Clinical evaluation, systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR), in supine and standing positions, were obtained before and every two weeks, first two in placebo, during 12 weeks. Laboratory data, hemogram, sodium, potassium, urea, creatinine, glucose, hepatic aminotransferases and urinalysis, were done and at end of study. Hemodynamic monitorization was performed by Swan-Ganz catheter in pulmonary artery to obtain RAP and PAWP, in mmHg. Cardiac output (CO) was obtained by thermodilution method. Systemic vascular resistance (SVR) arose from variables above. Hemodynamic variables were measured at 2nd and 12th weeks during treatment with 50mg of chlorthalidone each 48 h. RESULTS: A significant reduction of SBP (p = 0.005 and p = 0.003), DBP (p < 0.0001 and p < 0.0001), respectively in supine and standing positions. HR did not show statistical difference. At hemodynamic monitoring was observed a significative reduction of SVR (p < 0.02), but not with CO. CONCLUSION: Chlorthalidone in low dosis was effective to treat mild SAH, basically by lowering SVR.

Adult↗

PubMed1993

[Effect of treatment with chlorthalidone on reduction of left ventricular mass in patients with systemic arterial hypertension].

PURPOSE: To evaluate the effects of the use of chlorthalidone on left ventricular mass of patients with mild and moderate systemic arterial hypertension (SAH). METHODS: Twenty-nine patients with mild and moderate SAH were studied with mean age of 48.4 years and 16 men. Clinical evaluation, systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR), in supine and standing positions, were obtained before and every 3 weeks, after 2 with placebo, during 12 weeks of treatment with 50mg of chlorthalidone each 48 hours. Laboratory data (hemogram, sodium, potassium, urea creatinine, glucose, hepatic aminotransferases and urinalysis) were done before and at end of study. Echocardiographic study was performed by M-mode before and after 6 and 12 weeks of treatment, and obtained the following data: diastolic diameter (DdLV), diastolic septum (DSTLV) and posterior wall thickness (PWTLV) of left ventricle. The left ventricular mass (LVM) was calculated by the formula: LVM = (DSTLV+PWTLV+DdLVE)3 - (DdLV)3 x 1.05/body surface, in g/m2. RESULTS: A significant reduction of SBP (p < 0.0001), DBP (p < 0.001) in supine and standing positions. HR did not show statistical difference. At echocardiographic study, M-mode, was observed a significant reduction of LVM after 12 weeks of treatment (181 +/- 67 to 156 +/- 34 g/m2, p < 0.01). CONCLUSION: Chlorthalidone was effective to control blood pressure and to reduce LVM of patients with SAH.

Adult↗

PubMed1998

Comparison of chlorthalidone, propranolol and bopindolol in six-month treatment of arterial hypertension.

The aim of this study was to test the hypothesis that prolonged treatment of mild to moderate hypertension with low-dose thiazide diuretics or beta blockers does not induce any of the major untoward biochemical changes, such as hypertriglyceridemia, hypercholesterolemia, hyperuricemia and electrolyte imbalances. The effect of these drugs was analyzed in 100 outpatients (52 males and 48 females) aged 52.0 +/- 7.9 years with mild to moderate hypertension, in a prospective 6-month study. After an appropriate workup, the patients were randomized to either 25 mg chlorthalidone (40 patients), 120 mg propranolol (30 patients), or 2 mg per day bopindolol (30 patients). A significant reduction of approximately 10% in systolic and diastolic blood pressure was recorded in all the groups. At the end of the 6th month, in the chlorthalidone group triglycerides increased to 3.0 +/- 2.1 mmol/l from 2.8 +/- 1.6 mmol/l, while cholesterol after an initial increase to 6.6 +/- 1.6 from 6.4 +/- 1.6 mmol/l returned to the baseline level. Uricemia and serum potassium concentration decreased by 4%. The body weight was reduced to 83.8 +/- 13.4 kg from 86.1 +/- 13.4 kg. There was no change in serum glucose level. In the propranolol group, as expected, heart rate decreased by 20%, but there were no significant changes in glucose and potassium plasma concentration. Triglycerides did not change significantly, while cholesterol, after a small increase, returned to the initial levels. Similar results were obtained in the bopindolol group, apart from the triglycerides, which increased significantly (to 2.5 +/- 1.1 from 2.2 +/- 0.4 mmol/l), probably because of the lower baseline concentration. We conclude that in prolonged treatment, chlorthalidone, propranolol and bopindolol do not induce significant untoward biochemical changes that alone might increase cardiovascular risk.

Adult↗

PubMed1979

Metoprolol with and without chlorthalidone in hypertension.

After a control period on a placebo, 45 patients with mild to moderate hypertension were treated with metoprolol, 100 mg twice daily alone and in free combination with chlorthalidone 50 mg daily using a double-blind crossover technique. The beta-blocker alone induced a significant fall in blood pressure; the diastolic pressure was reduced to 100 mg Hg or less in 37 of the 45 patients and to 95 mm Hg or less in 19 patients. The addition of chlorthalidone enhanced the antihypertensive effect so that in 33 patients diastolic pressure fell to 95 mm Hg or less. The drugs were well tolerated even by a small number of patients with chronic bronchitis and diabetes mellitus. None of the patients developed cardiac failure. Adding a diuretic caused a small reduction in serum potassium concentrations, and the relevance of this observation is discussed.

Adult↗

PubMed1980

Blood pressure response to a single daily dose of a clonidine-chlorthalidone combination.

A single evening dose of a clonidine-chlorthalidone combination (Combipres) was compared with the usual twice-daily schedule in 11 patients with essential hypertension. No significant difference was found between the blood pressures recorded on the two regimens or between morning and afternoon pressures on the once-daily schedule. Only one patient did not maintain adequate blood pressure control. We suggest that some patients with essential hypertension can be adequately treated with a single daily dose of a combination of clonidine and chlorthalidone.

Adolescent↗