CONCOMITANT CONSIDERATIONS IN LONG-TERM ANTIHYPERTENSIVE TREATMENT

Even with antihypertensive therapy, the risks in hypertensive patients, especially the incidence of coronary events, cannot be lowered to that of the normotensive population. Therefore, the metabolic effects of long-term therapy on lipid metabolism and the efficacy of antihypertensive drugs to lower blood pressure were studied as possible explanations for this partial therapeutic failure. Hypertensive patients who participated in long-term trial provided a unique opportunity to observe the effects of long-term treatment and of then discontinuing antihypertensive therapy. During treatment, increases in total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides following hydrochlorothiazide, and increases of LDL-C and triglycerides and a decrease of high-density lipoprotein cholesterol (HDL-C) following atenolol were observed up to 42 months. After 5.2 +/- 1.4 years of randomised antihypertensive treatment, cessation of hydrochlorothiazide led to a decrease of total cholesterol from 6.40 to 5.98 mmol/l and of LDL-C from 4.33 to 3.89 mmol/l. After discontinuation of atenolol, LDL-C decreased from 4.20 to 3.89 mmol/l and triglycerides from 2.21 to 1.91 mmol/l, whereas HDL-C increased from 0.96 to 1.17 mmol/l (all differences significant). Thus the adverse effects of both agents persisted for more than five years and were reversible after medication was discontinued. In recent years titration to the lowest possible dose of antihypertensive agents has been suggested to avoid adverse metabolic alterations and subjective side effects. In a comparative trial lasting one year, with doses currently used in antihypertensive therapy, verapamil (120 to 480 mg/day) had an almost two-fold higher response rate as compared with hydrochlorothiazide (12.5 to 50 mg/day) as a single agent and in combination in mild to moderate hypertension. Thus, our studies have shown that the well-known adverse effects of diuretics and beta-blockers on lipid metabolism persist for more than five years when these agents are used in the previously prescribed rather high doses. Furthermore, the strategy of low dose therapy in order to avoid adverse effects of the agents might result in the administration of submaximally effective doses. In addition, because of a more pronounced antihypertensive effect and similar rates of withdrawal from therapy, the calcium antagonist verapamil must be regarded as clearly superior to the diuretic hydrochlorothiazide.