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Adverse effects of long term diuretic antihypertensive therapy Diuretic drugs are widely used as first- or second- line antihypertensive therapy, being both effective and safer than most other drugs. However, although the incidence of deaths from cerebrovascular accidents has decreased, little improvement has occurred in mortality from myocardial infarction andl or sudden death. Patients with untreated hypertension entered a study to examine the possibility that diuretics induce changes in electrolyte metabolism that may cause arrhythmias and thus sudden death and cause a myocardial infarct to become a fatal occurrence. Normotensive patients (diastoliC BP < 95mm Hg) remained untreated, patients with diastolic BP 95- 109mm Hg randomly received no therapy, sodium restriction, chlorothiazide + methyldopa or propranolol followed by chlorothiazide if necessary, while patients with diastolic BP ;al: 110mm Hg received chlorothiazide + methyldopa,or propranolol supplemented with chlorothiazide as required. Mortality was higher in patients initially treated with a thiazide diuretic and in patients with diastoliC BP 95-109mm Hg, apparentfy because of a greater number of deaths from myocardial infarction or sudden death. The mortality increase occurred in the initial 2 years, but between 2 and 10 years after therapy started. the death rate was similar and mortality from nonvascular and vascular events was similar in the different groups. Patients receiving sole diuretic therapy had a higher death rate but more effective BP control than those receiving combination treatment. Propranolol alone controlled 8P in about 60% of cases and in the 57 patients requiring additional chlorothiazide, there was no evidence of any increase in mortality at any stage. Changes in electrolyte homeostasis, especially of potassium, magnesium and hydrogen ions, appear to be the most likely explanation for the higher mortality among the diuretic-treated patients. Although plasma potassium levelS did not appear depressed in this study cellular levels may have been reduced, leading to reduced plasma levels in times of stress. High plasma potassium and magnesium levels can be achieved by low doses of diuretics combined with a diet low in sodium and high in potassium or by using potassium-sparing diuretics together with thiazide diuretics. Otherwise death may be prevented by avoiding the stress-induced changes, which could be achieved by peripheral blockage or reducing sympathetic outflow. Margan. T et al.: Joumal of Cardiovascular Pharmacology 6 (Suppl. 1).' S269 (1984) 2 Reactions 10 Nov 1984 0157-7271/84/1110-0002/0$01.0010 © ADIS Press

Adverse effects of long term diuretic antihypertensive therapy

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Adverse effects of long term diuretic antihypertensive therapy

Diuretic drugs are widely used as first- or second­line antihypertensive therapy, being both effective and safer than most other drugs. However, although the incidence of deaths from cerebrovascular accidents has decreased, little improvement has occurred in mortality from myocardial infarction andl or sudden death.

Patients with untreated hypertension entered a study to examine the possibility that diuretics induce changes in electrolyte metabolism that may cause arrhythmias and thus sudden death and cause a myocardial infarct to become a fatal occurrence. Normotensive patients (diastoliC BP < 95mm Hg) remained untreated, patients with diastolic BP 95-109mm Hg randomly received no therapy, sodium restriction, chlorothiazide + methyldopa or propranolol followed by chlorothiazide if necessary, while patients with diastolic BP ;al: 110mm Hg received chlorothiazide + methyldopa,or propranolol supplemented with chlorothiazide as required.

Mortality was higher in patients initially treated with a thiazide diuretic and in patients with diastoliC BP 95-109mm Hg, apparentfy because of a greater number of deaths from myocardial infarction or sudden death. The mortality increase occurred in the initial 2 years, but between 2 and 10 years after therapy started. the death rate was similar and mortality from nonvascular and vascular events was similar in the different groups. Patients receiving sole diuretic therapy had a higher death rate but more effective BP control than those receiving combination treatment. Propranolol alone controlled 8P in about 60% of cases and in the 57 patients requiring additional chlorothiazide, there was no evidence of any increase in mortality at any stage.

Changes in electrolyte homeostasis, especially of potassium, magnesium and hydrogen ions, appear to be the most likely explanation for the higher mortality among the diuretic-treated patients. Although plasma potassium levelS did not appear depressed in this study cellular levels may have been reduced, leading to reduced plasma levels in times of stress. High plasma potassium and magnesium levels can be achieved by low doses of diuretics combined with a diet low in sodium and high in potassium or by using potassium-sparing diuretics together with thiazide diuretics. Otherwise death may be prevented by avoiding the stress-induced changes, which could be achieved by peripheral blockage or reducing sympathetic outflow. Margan. T et al.: Joumal of Cardiovascular Pharmacology 6 (Suppl. 1).' S269 (1984)

2 Reactions 10 Nov 1984 0157-7271/84/1110-0002/0$01.0010 © ADIS Press