[The optimal combination of captopril and hydrochlorothiazide in mild hypertension.]

We have previously shown that in the treatment of mild to moderate hypertension little is gained by increasing the dose of hydrochlorothiazide (HCT) over 12.5 mg when combined with an ACE-inhibitor. An increase in dosing was associated with more numerous side effects. The present study was designed to explore the relative efficacy of 12.5 and 6.25 mg of HCT in combination with captopril (C).

For the study 25 patients with mild hypertension were recruited. Their mean age was 63 years (SD +/- 13 years). After a four week wash-out period and a dose finding phase of eight weeks, eight patients were stabilised at a diastolic pressure of <95 mmHg on C 50 mg + HCT 12.5 mg and 17 on C 25 mg + HCT 12.5 mg. These doses of C were continued throughout the study. The patients were then divided in two groups, receiving 12.5 mg or 6.25 mg of HCT for four weeks. The groups were then crossed over and treated for a further four week period. Finally, placebo was given for HCT for four weeks.

Although the mean supine blood pressure was lower on HCT 6.25 mg than placebo by 5/3 mmHg this difference was not significant. The pressure fall on HCT 12.5 mg in comparison with placebo was significant (9/7 mmHg, p<0.02) and the supine systolic blood pressure was similarly significantly lower on HCT 12.5 mg than 6.25 mg (p<0.02). The mean serum-K was significantly reduced by HCT 12.5 mg but only two patients had values below 3.5 mmol/1 and none below 3.0 mmol/1. No change was observed in serum creatinine values. No significant increase was reported in side effects on HCT + C in comparison with placebo + C.

This and our previous studies suggest an optimal dose of HCT of approximately 12.5 mg. A dose of 6.25 mg may not be without an antihypertensive effect. However, such an effect is likely to be modest.