Long-term diuretic therapy: effects of dose reduction on antihypertensive efficacy and counterregulatory systems

In the present study, the effects of a dose reduction on antihypertensive efficacy and metabolic side effects of diuretic therapy were investigated in 36 hypertensive patients. During the first treatment period of 1 year, the patients were treated with 25 mg of the thiazide diuretic bemetizide (n = 18) or 25 mg bemetizide plus 50 mg of the potassium-sparing agent triamterene (n = 18). Mean blood pressure (BP) values decreased significantly (p less than 0.01) during the first year of the trial. Thereafter, doses were reduced to 10 mg bemetizide or 10 mg bemetizide plus 20 mg triamterene in patients whose BP became normal during the first year (n = 16 in both groups). At the end of the second year, equal BP control was achieved with doses more than twice smaller than those used during the first year. During the second year of the trial, activation of the renin-angiotensin system (RAS) was significantly less pronounced as compared with the first year and the percentage of patients with hypokalemia (less than 3.5 mM) decreased from 62.5 to 25% in the bemetizide group. Thus, this long-term study provides additional evidence that diuretics have a flat dose-response curve with respect to their antihypertensive efficacy, whereas lower doses might cause less pronounced activation of counter-regulatory systems. Furthermore, our results indicate that long-term studies might be necessary to assess the full antihypertensive potential of low doses of antihypertensive agents.