Management of hypertension: the role of combination therapy

The complementary action of angiotensin converting enzyme inhibitors and 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 pressure while minimizing the dose-dependent adverse effects of HCTZ, such as hypotension and its metabolic effects on plasma lipoproteins, by keeping the dose of each agent to the minimum. Fosinopril has a unique dual mechanism of elimination and can therefore be used in patients with renal impairment. The efficacy of the combination of fosinopril and hydrochlorothiazide compared with placebo and other agents is reviewed in this article. Studies have demonstrated that the combination is effective in the elderly and in renally impaired patients, regardless of severity. In addition, in non-insulin dependent diabetes, antihypertensive effect is achieved without further affecting carbohydrate and lipid metabolism, which is often the case when thiazide diuretics alone are used. A matrix study was performed to evaluate the optimum dose combination to produce blood pressure normalization and minimize side effects. This study evaluated 17 different dose combinations and demonstrated that the lowest dose combination to produce a clinically significant effect was fosinopril 10 mg and HCTZ 12.5 mg. However, a dose-related antihypertensive effect can be seen, giving the option for the use of 20 mg fosinopril for moderately hypertensive patients. Both combination therapy and fosinopril were significantly more effective than HCTZ alone or placebo. The fosinopril/HCTZ combination has also been shown to have a comparable effect to sustained-release nifedipine and propanolol + HCTZ. The studies reviewed here demonstrate that fosinopril/HCTZ combination treatment has a number of advantages over either agent used alone, providing blood pressure normalization in a broad range of hypertensive patients, including diabetic patients and the elderly.