Once-daily administration of captopril plus hydrochlorothiazide in patients with essential hypertension. A biometrical approach for investigating its effects on blood-pressure circadian rhythm

The aim of the study was to verify the duration of the effect of a fixed combination of captopril (50 mg) and hydrochlorothiazide (25 mg), in a once-daily regimen, in 25 patients with mild to moderate essential hypertension (14 men [mean age, 50.4 ± 8.8 years], 11 women [mean age, 48.8 ± 10.2 years]). After 15 days on placebo, 24-hour ambulatory blood-pressure monitoring was performed. The synergistic combination of captopril plus hydrochlorothiazide was then given between 8 and 9 AM. After 30 days of therapy, 24-hour blood pressure monitoring was performed a second time. An explorative analysis was effected on both mean blood pressure and mean heart rate; the 24 hours were divided into day and night periods (A: 24 hours; B: 7 AM to 11 PM; C: 11 PM to 7 AM. All patients showed a decrease in mean systolic/diastolic pressure (from 151/91 ± 14/8 mmHg to 139/82 ± 10/6 mmHg (A); 154/94 ± 14/8 mmHg to 142/84 mmHg to 142/84 ± 10/6 mmHg (B); and 140/83 ± 16/9 mmHg to 129/77 ± 13/7 mmHg (C). In men, mean systolic/diastolic pressure changed from 153/92 ± 12/5 mmHg to 138/83 ± 6/4 mmHg (A); 156/94 ± 13/5 mmHg to 140/84 ± 6/4 mmHg (B); and 142/84 ± 12/6 mmHg to 131/78 ± 9/5 mmHg (C). In women, mean systolic/diastolic pressure decreased from 149/91 ± 16/11 mmHg to 140/82 ± 14/7 mmHg (A); 152/94 ± 15/11 mmHg to 144/84 ± 13/8 mmHg (B); and 138/82 ± 21/11 mmHg to 127/75 ± 17/8 mmHg (C)). The regimen did not affect heart rate in any period. Data were then analyzed on a global level. A periodic asymmetrical model with three harmonics was carried out on all the data obtained. Systolic and diastolic blood pressure data from all patients treated with captopril plus hydrochlorothiazide in comparison with the placebo values showed a lowering translation of the profiles analyzed by mean levels, from 151/92 mmHg to 139/83 mmHg in all patients (from 152/92 mmHg to 139/83 mmHg in men, and from 150/92 mmHg to 140/82 mmHg in women). The comparisons in the mean levels are significant for both systolic and diastolic patterns (P < 0.001). We also observed that the circadian rhythm was unaffected.