Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

Abstract

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.

Your institute does not have access to this article

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1
Figure 2

References

  1. Mancia G, Grassi G . Rationale for the use of a fixed combination in the treatment of hypertension. Eur Heart J 1999; 1 (Suppl): L14–L19.

    Google Scholar 

  2. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288: 2981–2997.

  3. Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998; 351: 1755–1762.

    CAS  Article  Google Scholar 

  4. Brown MJ, Palmer CR, Castaigne A, deLeeuw PW, Mancia G, Rosenthal T et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 2000; 356: 366–372.

    CAS  Article  Google Scholar 

  5. Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995–1003.

    Article  Google Scholar 

  6. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JAMA 2003; 289: 2560–2572.

    CAS  Article  Google Scholar 

  7. Guidelines Committee. 2003 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–1053.

  8. Khan NA, McAlister FA, Lewanczuk RZ, Touyz RM, Padwal R, Rabkin SW et al. The 2005 Canadian Hypertension Education Program recommendations for the management of hypertension: Part II – therapy. Can J Cardiol 2005; 21 (8): 657–672.

    PubMed  Google Scholar 

  9. Safar M, Zanchetti A, Sever PS, Anlauf M, Calvo Gomez C, De Leeuw PW et al. Perindopril and indapamide as a combination therapy in the treatment of mild to moderate hypertension. A double-blind, randomized, placebo-controlled European multi-centre study. Eur Heart J 1994; 15 (Suppl): 195.

    Google Scholar 

  10. Myers MG, Asmar R, Leenen FH, Safar M . Fixed low-dose combination therapy in hypertension – a dose response study of perindopril and indapamide. J Hypertens 2000; 18: 317–325.

    CAS  Article  Google Scholar 

  11. Myers MG, Leenen FHH, Tanner J . Assessment of the first line low-dose combination of perindopril 2 mg+indapamide 0.625 mg using the missed dose technique. J Hypertension 2003; 21: S178.

    Article  Google Scholar 

  12. Myers MG, Leenen FHH . Persistence of the antihypertensive effect of low-dose combination therapy in mild hypertension. Blood Pressure (in press).

  13. Sackett DL . The hypertensive patient: 5. Compliance with therapy. Can Med Assoc J 1979; 121: 259–261.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Chrysant SG, McDonald RH, Wright JT, Barden PL, Weiss RJ, for the Perindopril Study Group. Perindopril as monotherapy in hypertension: a multicenter comparison of two dosing regimens. Clin Pharmacol Ther 1993; 53: 479–484.

    CAS  Article  Google Scholar 

  15. Ménard J, Bellet M, Brunner HR . Clinical development of antihypertensive drugs: can we perform better? In: Laragh JH, Brenner BM (eds). Hypertension: Pathophysiology, Diagnosis and Management, 1st edn. Raven Press Limited: New York, 1990, pp 2331–2350.

    Google Scholar 

  16. Vaur L, Dutrey-Dupagne C, Boussac J, Genes N, Bouvier d'Yvoire M, Elkik F et al. Differential effects of a missed dose of trandolapril and enalapril on blood pressure control in hypertensive patients. J Cardiovas Pharmacol 1995; 26: 127–131.

    CAS  Article  Google Scholar 

  17. McCarron D, The Ramipril Multicenter Study Group. 24-Hour blood pressure profiles in hypertensive patients administered ramipril or placebo once daily: magnitude and duration of antihypertensive effects. Clin Cardiol 1991; 14: 737–742.

    CAS  Article  Google Scholar 

  18. Mansoor GA, McCabe EJ, White WB . Long-term reproducibility of ambulatory blood pressure. J Hypertens 1994; 12: 703–708.

    CAS  Article  Google Scholar 

  19. Palatini P, Mormino P, Canali C, Santonastaso M, De Venuto G, Zanata G et al. Factors affecting ambulatory blood pressure reproducibility. Results of the HARVEST trial. Hypertension 1994; 23: 211–216.

    CAS  Article  Google Scholar 

  20. Leenen FHH, Myers MG, Joyner CD, Toal CB . Differential effects of once-daily antihypertensive drugs on blood pressure, left ventricular mass and sympathetic activity: nifedipine-GITS versus felodipine-ER versus enalapril. Can J Cardiol 2002; 18: 1285–1293.

    CAS  PubMed  Google Scholar 

  21. Leenen FH, Forney A, Notman G, Tanner J . Persistence of anti-hypertensive effect after ‘missed doses’ of calcium antagonist with long (amlodipine) vs short (diltiazem) elimination half-life. Br J Clin Pharmacol 1996; 41: 83–88.

    CAS  Article  Google Scholar 

  22. Smilde JG . A comparison of amlodipine and felodipine extended release in the treatment of hypertension at steady state and after two missed doses. Curr Ther Res 1997; 58: 141–153.

    CAS  Article  Google Scholar 

  23. Tan KW, Leenen FH . Persistence of anti-hypertensive effect after missed dose of perindopril. J Clin Pharmacol 1999; 48: 628–629.

    CAS  Article  Google Scholar 

  24. Skoularigis J, Strugo V, Chopamba A, Setekge S, Sareli P . Low dose hydrochlorothiazide (12.5 to 25 mg daily) as monotherapy in black patients with mild to moderate hypertension. Assessment by ambulatory blood pressure monitoring. Am J Hypertens 1995; 8: 1046–1050.

    CAS  Article  Google Scholar 

  25. Wiggam MI, Bell PM, Sheridan B, Walmsley A, Atkinson AB . Low dose bendrofluazide (1.25 mg) effectively lowers blood pressure over 24 h. Am J Hypertens 1999; 12: 528–531.

    CAS  Article  Google Scholar 

  26. Resplandy G, Genissel P . Pharmacokinetics of perindopril in high-risk populations. J Cardiovasc Pharmacol 1991; 18 (Suppl 7): S9–S18.

    Article  Google Scholar 

  27. Matheson AJ, Cheer SM, Goa KL . Perindopril/indapamide 2/0.625 mg/day-a review of its place in the management of hypertension. Drugs 2001; 6: 1211–1229.

    Article  Google Scholar 

  28. Bussien J-P, d'Amore TF, Perret L, Porche M, Nussberger J, Waeber B et al. Single and repeated dosing of the converting enzyme inhibitor perindopril to normal subjects. Clin Pharmacol Ther 1986; 39: 554–558.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to M G Myers.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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). https://doi.org/10.1038/sj.jhh.1002107

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1002107

Keywords

  • perindopril
  • indapamide
  • antihypertensive therapy

Further reading

Search

Quick links