MANAGEMENT OF HYPERTENSION - THE ROLE OF COMBINATION THERAPY

The complementary action of angiotensin converting enzyme inhibitors a nd diuretics in the treatment of hypertension has been demonstrated in a number of studies of fosinopril and hydrochlorothiazide (HCTZ). The combination provides a clinically significant reduction in blood pres sure while minimizing the dose-dependent adverse effects of HCTZ, such as hypotension and its metabolic effects on plasma lipoproteins, by k eeping the dose of each agent to the minimum. Fosinopril has a unique dual mechanism of elimination and can therefore be used in patients wi th renal impairment. The efficacy of the combination of fosinopril and hydrochlorothiazide compared with placebo and other agents is reviewe d in this article. Studies have demonstrated that the combination is e ffective in the elderly and in renally impaired patients, regardless o f severity. In addition, in non-insulin dependent diabetes, antihypert ensive effect is achieved without further affecting carbohydrate and l ipid metabolism, which is often the case when thiazide diuretics alone are used, A matrix study was performed to evaluate the optimum dose c ombination to produce blood pressure normalization and minimize side e ffects. This study evaluated 17 different dose combinations and demons trated that the lowest dose combination to produce a clinically signif icant effect was fosinopril 10 mg and HCTZ 12.5 mg. However, a dose-re lated antihypertensive effect can be seen, giving the option for the u se of 20 mg fosinopril for moderately hypertensive patients. Both comb ination therapy and fosinopril were significantly more effective than HCTZ alone or placebo. The fosinopril/HCTZ combination has also been s hown to have a comparable effect to sustained-release nifedipine and p ropanolol + HCTZ. The studies reviewed here demonstrate that fosinopri l/HCTZ combination treatment has a number of advantages over either ag ent used alone, providing blood pressure normalization in a broad rang e of hypertensive patients, including diabetic patients and the elderl y. (C) 1997 American Journal of Hypertension, Ltd.