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Effects of high dose olmesartan medoxomil plus hydrochlorothiazide on blood pressure control in patients with grade 2 and grade 3 hypertension

Journal of Human Hypertension volume 25, pages 565–574 (2011)Cite this article

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Abstract

High dose (40 mg) olmesartan medoxomil (OM) blocks the angiotensin II receptor, significantly reducing blood pressure (BP). Adding hydrochlorothiazide (HCTZ) to OM increases efficacy, but has not been evaluated in patients inadequately controlled by OM 40 mg. Patients with grade 2 and grade 3 hypertension with inadequately controlled BP (seated diastolic blood pressure [SeDBP] 90–115 mm Hg and seated systolic blood pressure [SeSBP] 140–180 mm Hg, plus ambulatory BP criteria) after 8 weeks of OM 40 mg open-label treatment were randomized to 8 weeks of double-blind treatment with OM/HCTZ 40/25 (n=140), 40/12.5 (n=278), 20/12.5 mg (n=280) or OM 40 mg (n=274). Treatment with OM/HCTZ 40/25 mg and 40/12.5 mg significantly reduced SeDBP (−5.3 and −3.4 mm Hg, respectively), and SeSBP (−7.4 and −5.2 mm Hg, respectively), vs OM 40 mg monotherapy (P<0.0001 for each) in patients inadequately controlled on OM 40 mg alone. OM/HCTZ 40/12.5 mg reduced SeSBP significantly more than OM/HCTZ 20/12.5 mg (−2.6 mm Hg, P=0.0255), and also produced a further reduction in SeDBP vs the lower dose. All treatments were well tolerated, with similar low proportions of patients reporting treatment-emergent adverse events in all treatment groups. In conclusion, adding HCTZ to OM 40 mg significantly improves BP reductions and target BP rates in harder-to-treat patients and a clear dose-response was observed for efficacy.

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References

  1. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R . Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903–1913.

    Article  Google Scholar 

  2. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003; 289: 2560–2572.

    Article  CAS  Google Scholar 

  3. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G et al. 2007 guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of hypertension (ESH) and of the european society of cardiology (ESC). J Hypertens 2007; 25: 1105–1187.

    Article  CAS  Google Scholar 

  4. Mancia G, Laurent S, Agabiti-Rosei E, Ambrosioni E, Burnier M, Caulfield MJ et al. Reappraisal of European guidelines on hypertension management: a European Society of hypertension task force document. J Hypertens 2009; 27: 2121–2158.

    Article  CAS  Google Scholar 

  5. Pereira M, Lunet N, Azevedo A, Barros H . Differences in prevalence, awareness, treatment and control of hypertension between developing and developed countries. J Hypertens 2009; 27: 963–975 (online early section).

    Article  CAS  Google Scholar 

  6. Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National kidney foundation hypertension and diabetes executive committees working group. Am J Kidney Dis 2000; 36: 646–661.

    Article  CAS  Google Scholar 

  7. Fabia MJ, Abdilla N, Oltra R, Fernandez C, Redon J . Antihypertensive activity of angiotensin II AT1 receptor antagonists: a systematic review of studies with 24 h ambulatory blood pressure monitoring. J Hypertens 2007; 25: 1327–1336.

    Article  CAS  Google Scholar 

  8. Maillard MP, Wurzner G, Nussberger J, Centeno C, Burnier M, Brunner HR . Comparative angiotensin II receptor blockade in healthy volunteers: the importance of dosing. Clin Pharmacol Ther 2002; 71: 68–76.

    Article  CAS  Google Scholar 

  9. Hasler C, Nussberger J, Maillard M, Forclaz A, Brunner HR, Burnier M . Sustained 24-h blockade of the renin-angiotensin system: a high dose of a long-acting blocker is as effective as a lower dose combined with an angiotensin-converting enzyme inhibitor. Clin Pharmacol Ther 2005; 78: 501–507.

    Article  CAS  Google Scholar 

  10. Jones MR, Sealey JE, Laragh JH . Effects of angiotensin receptor blockers on ambulatory plasma Renin activity in healthy, normal subjects during unrestricted sodium intake. Am J Hypertens 2007; 20: 907–916.

    Article  CAS  Google Scholar 

  11. Sellin L, Stegbauer J, Laeis P, Rump LC . Adding hydrochlorothiazide to olmesartan dose dependently improves 24-h blood pressure and response rates in mild-to-moderate hypertension. J Hypertens 2005; 23: 2083–2092.

    Article  CAS  Google Scholar 

  12. Mancia G, Grassi G . Systolic and diastolic blood pressure control in antihypertensive drug trials. J Hypertens 2002; 20: 1461–1464.

    Article  CAS  Google Scholar 

  13. Coltamai L, Maillard M, Simon A, Vogt B, Burnier M . Comparative vascular and renal tubular effects of angiotensin II receptor blockers combined with a thiazide diuretic in humans. J Hypertens 2010; 28: 520–526.

    Article  CAS  Google Scholar 

  14. Le MT, Pugsley MK, Vauquelin G, Van Liefde I . Molecular characterisation of the interactions between olmesartan and telmisartan and the human angiotensin II AT1 receptor. Br J Pharmacol 2007; 151: 952–962.

    Article  CAS  Google Scholar 

  15. Brunner HR, Stumpe KO, Januszewicz A . Antihypertensive efficacy of olmesartan medoxomil and candesartan cilexetil assessed by 24-h ambulatory blood pressure monitoring in patients with essential hypertension. Clin Drug Invest 2003; 23: 419–430.

    Article  CAS  Google Scholar 

  16. Oparil S, Williams D, Chrysant SG, Marbury TC, Neutel J . Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension. J Clin Hypertens (Greenwich) 2001; 3: 283–291–318.

    Article  CAS  Google Scholar 

  17. Nakayama S, Watada H, Mita T, Ikeda F, Shimizu T, Uchino H et al. Comparison of effects of olmesartan and telmisartan on blood pressure and metabolic parameters in Japanese early-stage type-2 diabetics with hypertension. Hypertens Res 2008; 31: 7–13.

    Article  CAS  Google Scholar 

  18. Pickering TG . When and how to use self (home) and ambulatory blood pressure monitoring. J Am Soc Hypertens 2008; 2: 119–124.

    Article  Google Scholar 

  19. Staessen JA, Thijs L, Fagard R, O'Brien ET, Clement D, de Leeuw PW et al. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic hypertension in Europe trial Investigators. JAMA 1999; 282: 539–546.

    Article  CAS  Google Scholar 

  20. Sega R, Facchetti R, Bombelli M, Cesana G, Corrao G, Grassi G et al. Prognostic value of ambulatory and home blood pressures compared with office blood pressure in the general population: follow-up results from the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. Circulation 2005; 111: 1777–1783.

    Article  Google Scholar 

  21. White WB . Circadian variation of blood pressure: clinical relevance and implications for cardiovascular chronotherapeutics. Blood Press Monit 1997; 2: 47–51.

    CAS  PubMed  Google Scholar 

  22. Turnbull F . Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 2003; 362: 1527–1535.

    Article  CAS  Google Scholar 

  23. Sawada T, Yamada H, Dahlof B, Matsubara H . Effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high cardiovascular risks: KYOTO HEART Study. Eur Heart J 2009; 30: 2461–2469.

    Article  CAS  Google Scholar 

  24. Schrader J, Luders S, Kulschewski A, Hammersen F, Plate K, Berger J et al. Morbidity and mortality after stroke, eprosartan compared with nitrendipine for secondary prevention: principal results of a prospective randomized controlled study (MOSES). Stroke 2005; 36: 1218–1226.

    Article  CAS  Google Scholar 

  25. Volpe M, Tocci G, Sciarretta S, Verdecchia P, Trimarco B, Mancia G . Angiotensin II receptor blockers and myocardial infarction: an updated analysis of randomized clinical trials. J Hypertens 2009; 27: 941–946.

    Article  CAS  Google Scholar 

  26. Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547–1559.

    Article  CAS  Google Scholar 

  27. Elliott WJ, Meyer PM . Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet 2007; 369: 201–207.

    Article  CAS  Google Scholar 

  28. Burnier M, Brunner HR . Angiotensin II receptor antagonists. Lancet 2000; 355: 637–645.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge the efforts of all of the investigators who participated in this study. This study was sponsored by Daiichi Sankyo Europe GmbH. We also thank Dr Phil Jones of in Science Communications who provided medical writing support funded by Daiichi Sankyo Europe GmbH.

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Authors and Affiliations

  1. Department of Internal Medicine/Nephrology, Heinrich-Heine-University Dusseldorf, Dusseldorf, Germany

    L C Rump, L Sellin & J Stegbauer

  2. Service Endocrinologie Prévention Vasculaire, Hôpital de La Pitié, Paris, France

    X Girerd

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  1. L C Rump
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Correspondence to L C Rump.

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Competing interests

LCR has received honoraria from Daiichi Sankyo for talks and consultancy.

XG, in the past 3 years has been paid speakers's fees or travel costs by BMS, Boehringer Ingelheim, Daiichi Sankyo, Ipsen, Novartis, Pfizer, Sanofi Aventis and Takeda. XG has been paid consulting fees by Novartis, Daiichi Sankyo and Boehringer Ingelheim.

LS: no conflicts of interest.

JS: no conflicts of interest.

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Rump, L., Girerd, X., Sellin, L. et al. Effects of high dose olmesartan medoxomil plus hydrochlorothiazide on blood pressure control in patients with grade 2 and grade 3 hypertension. J Hum Hypertens 25, 565–574 (2011). https://doi.org/10.1038/jhh.2010.105

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