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The impact of one or two missed doses on the duration of action of combined perindopril and indapamide

A Corrigendum to this article was published on 19 June 2008


To evaluate the persistence of the antihypertensive effect of perindopril 4 mg+indapamide 1.25 mg once daily for up to 72 h using the ‘missed-dose’ technique. Hypertensive patients were initially treated with perindopril 2 mg+indapamide 0.625 mg once daily. After 4 weeks, the 135 of 216 patients who still had a diastolic BP85 mm Hg went on to receive perindopril 4 mg+indapamide 1.25 mg daily for a further 8 weeks. During either week 9 or 11, placebo was substituted for perindopril 4 mg+indapamide 1.25 mg on either one or two consecutive days to simulate BP changes, which might occur after one or two missed doses. A 24-h ambulatory BP recording was performed at baseline, after 9 or 11 weeks of perindopril+indapamide therapy and during the simulated missed doses, 24– 48 and 48–72 h after the administration of perindopril 4 mg+indapamide 1.25 mg. Significant (P<0.001) reductions in mean (±s.d.) 24-h ambulatory BP (mm Hg) during the first 24 h after perindopril 4 mg+indapamide 1.25 mg therapy versus baseline were noted for patients later randomized to the one missed dose (−15.9±10.5/−9.4±7.6) or two missed dose (−17.4±8.7/−10.3±5.1) sub-groups. A significant reduction in BP (P<0.001 versus baseline) was still present on the days when placebo was substituted for perindopril 4 mg+indapamide 1.25 mg with decreases in mean 24-h ambulatory BP from 24 to 48 h and 48 to 72 h after dosing being −11.9±10.1/−6.9±6.2 and −10.6±9.9/−5.8±5.7, respectively. Use of the ‘missed-dose’ technique has demonstrated a prolonged antihypertensive effect for perindopril 4 mg+indapamide 1.25 mg for up to 72 h, supporting the use of this combination as therapy for hypertension.

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Members of the General Practice Research Group who conducted the study include: AD Bell, J Cha, GM Fullerton, DJ Harterre, D Henry, V Martinho, BA Melbourne, MJ Mills, JL Nichols, JA Opie, I Siegel, DR Spink, K-W Tan, RK Tee, RJ Whatley, W Winzer, PA Zuliani. We would like to thank Ms Joanna Tanner, Coordinator of the General Practice Research Group, Dr Serge Carrière, Scientific Director and Mr René Hamel, Scientific Project Manager, Servier Canada Inc., for assistance with the organization of the study and Dr Marie-Claude Guertin (Montreal Heart Institute) for performing the data analyses. This study was supported by Servier Canada Inc. The authors (MG Myers and FHH Leenen) have received honoraria as speakers and consultants for Servier Canada Inc.

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Myers, M., Leenen, F. & on behalf of the General Practice Research Group. The impact of one or two missed doses on the duration of action of combined perindopril and indapamide. J Hum Hypertens 21, 86–93 (2007).

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  • perindopril
  • indapamide
  • antihypertensive therapy

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