Persistence of the antihypertensive effect of low‐dose combination therapy in mild hypertension

The persistence of the antihypertensive effect of perindopril 2 mg + indapamide 0.625 mg once daily for up to 72 h was evaluated using the "missed-dose" technique. After 4 weeks on perindopril 2 mg+indapamide 0.625 mg, 79 of 216 hypertensive patients at goal (diastolic blood pressure < 85 mmHg) continued on perindopril 2 mg+indapamide 0.625 mg for a further 8 weeks. During either week 9 or 11, placebo was substituted for perindopril 2 mg+indapamide 0.625 mg on either 1 day or on 2 consecutive days. Twenty-four-hour ambulatory blood pressure was recorded at baseline, after 9 or 11 weeks of perindopril 2 mg+indapamide 0.625 mg and during the simulated missed doses, 24-48 and 48-72 h after perindopril 2 mg+indapamide 0.625 mg. Significant (p < 0.001) reductions in mean (+/- SD) 24-h blood pressure (mmHg) during the first 24 h after perindopril 2 mg+indapamide 0.625 mg vs baseline were noted for the two sub-groups subsequently allocated to one missed dose (-13.5 +/- 10.4/-8.0 +/- 6.6) or two missed doses (-12.2 +/- 7.4/-6.9 +/- 4.2). The antihypertensive effect persisted (p < 0.001 to p < 0.05 vs baseline) on the days when placebo was substituted for perindopril 2 mg+indapamide 0.625 mg with reductions in mean 24-h blood pressure from 24-48 h and 48-72 h after dosing being -11.6 +/- 9.6/-6.3 +/- 6.4 and -6.4 +/- 6.0/-3.9 +/- 4.2, respectively. Use of the "missed-dose" technique demonstrated persistence of an antihypertensive effect for perindopril 2 mg + indapamide 0.625 mg for up to 72 h after dosing.