The role of low-dose diuretics in essential hypertension

Diuretics have been used to treat hypertension since 1958. The doses used were relatively high. Dose-dependent side effects and the increasing availability of other drugs such as beta- and alpha-blockers, calcium-entry blockers, and angiotensin-converting enzyme (ACE) inhibitors, with equal antihypertensive efficacy but additional effects in cardiovascular diseases, led to a decrease in diuretic use. In controlled trials, little or no protection against coronary artery disease (CAD) was discussed as being due to the diuretics' side effects. The main side effects are hypokalemia, hyperglycemia, and hyperlipidemia. Hypokalemia occurs most often (up to 30%) in thiazide-treated hypertensive patients, and may cause arrhythmias in patients with CAD. This side effect is clearly dose-dependent and may be avoided by comedication with antikaliuretics. Glucose intolerance may develop in about 3% of diuretic-treated men and is reversible after discontinuation of the diuretic. This side effect is functionally correlated with hypokalemia and therefore is not seen when patients are given a comedication (for example, spironolactone prevents hypokalemia). Hypercholesterolemia was first reported in 1964 during long-term diuretic treatment. During the first 12 weeks of treatment, low-density lipoprotein (LDL) cholesterol increased 5-15% in men and postmenopausal women. After 1 year of therapy, the levels decreased to pretreatment values. However, in placebo-controlled trials, the placebo groups exhibited cholesterol levels falling below the diuretic group. Although the mechanisms and the clinical implications of these side effects are not completely understood, the perception grew that diuretics per se may have been at least partially responsible for the lack of protection against CAD.(ABSTRACT TRUNCATED AT 250 WORDS)