Skip to main content
SpringerLink
Log in

Ambulatory monitoring of systolic hypertension in the elderly: Eprosartan/hydrochlorothiazide compared with losartan/hydrochlorothiazide (INSIST trial)

  • Original Research
  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

Introduction

Systolic hypertension is very common in the elderly and is strongly associated with the risk of cardiovascular and cerebrovascular events. The control of systolic hypertension is difficult and most patients require combination antihypertensive therapy. Few data are available regarding the efficacy of angiotensin II receptor antagonists on systolic hypertension of the elderly. The aim of this double-blind, double-dummy, randomized, parallel-group, multicenter study was to assess the efficacy of eprosartan 600 mg in combination with hydrochlorothiazide (HCTZ) 12.5 mg in comparison with losartan 50 mg in combination with HCTZ 12.5 mg, in reducing blood pressure in elderly patients with grade 2 systolic hypertension who did not optimally respond to eprosartan or losartan monotherapy.

Methods

After a 3-week placebo wash-out, 155 patients with an Office trough sitting systolic blood pressure (Office sitSBP) ≥160 mmHg and <180 mmHg were randomized to eprosartan 600 mg (n=78) or losartan 50 mg (n=77) once daily for 6 weeks. In patients not optimally responding to monotherapy (Office sitSBP≥130 mmHg) 12.5 mg HCTZ was added as fixed combination once daily for 6 weeks. A 24-hour ambulatory blood pressure monitoring (ABPM) was performed at the end of wash-out and at the end of the fixed-combination period.

Results

No statistically significant difference was found between eprosartan/HCTZ and losartan/HCTZ on the primary endpoint (24-hour ABPM SBP) with an adjusted mean difference between treatments of 3.1 mmHg (95% CI: −0.32–6.59). However, the mean 24-hour ABPM SBP significantly decreased by 16.7 mmHg with eprosartan/HCTZ and 20.3 mmHg with losartan/HCTZ (P<0.001 vs. baseline). The mean Office sitSBP significantly decreased by 28.7 mmHg and 29.6 mmHg respectively, with eprosartan/HCTZ and losartan/HCTZ (P<0.001 vs.baseline and vs. monotherapy).

Conclusion

In this study, eprosartan/HCTZ did not demonstrate to be superior to losartan/HCTZ in reducing ABPM systolic hypertension in the elderly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kannel WB, Gordon T, Schwarth MJ. Systolic vs. diastolic blood pressure and risk of coronary heart disease. The Framingham study. Am J Cardiol. 1971;27:335–346.

    Article  PubMed  CAS  Google Scholar 

  2. Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic, and cardiovascular risk: U.S. population data. Arch Intern Med. 1993;153:598–615.

    Article  PubMed  CAS  Google Scholar 

  3. Borghi C, Dormi A, Ambrosioni E, Gaddi A. Relative role of systolic, diastolic and pulse pressure as risk factors for cardiovascular events in the Brisighella Heart Study. J Hypertens. 2002;20:1737–1742.

    Article  PubMed  CAS  Google Scholar 

  4. Borghi C, Dormi A, L’Italien G, et al. The relationship between systolic blood pressure and cardiovascular risk - results of the Brisighella Heart Study. J Clin Hypertension. 2003;5:47–52.

    Article  Google Scholar 

  5. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Prospective Studies Collaboration. 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  PubMed  Google Scholar 

  6. Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet. 1997;350:757–764.

    Article  PubMed  CAS  Google Scholar 

  7. Mancia G, De Backer G, Dominiczak A, 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  PubMed  CAS  Google Scholar 

  8. Zanchetti A, Waeber B. Hypertension: which aspects of hypertension should we impact on and how? J Hypertens. 2006;24(suppl. 5):S2–S5.

    Article  CAS  Google Scholar 

  9. Mancia G, Bombelli M, Lanzarotti A, et al. Systolic vs diastolic blood pressure control in the hypertensive patients of the PAMELA population. Arch Int Med. 2002;162:582–586.

    Article  Google Scholar 

  10. Volpe M, Tocci G, Trimarco B, et al. Blood pressure control in Italy: results of recent surveys on hypertension. J Hypertens. 2007;25:1491–1498.

    Article  PubMed  CAS  Google Scholar 

  11. Chobanian AV. Isolated systolic hypertension in the elderly. N Engl J Med. 2007;357:789–796.

    Article  PubMed  CAS  Google Scholar 

  12. Hansson L, Zanchetti A, Carruthers SG, et al. for the HOT Study Group. 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.

    Article  PubMed  CAS  Google Scholar 

  13. Dahlöf B, Devereux RB, Kjeldsen SE, et al. LIFE Study Group. 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  PubMed  Google Scholar 

  14. Schrader J, Lüders S, Kulschewski A, 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;36:1218–1224.

    Article  PubMed  CAS  Google Scholar 

  15. Rosenthal T, Gavras I. Fixed-drug combinations as first-line treatment for hypertension. Prog Cardiovasc Dis. 2006;48:416–425.

    Article  PubMed  CAS  Google Scholar 

  16. Conlin PR, Spence JD, Williams B, et al. Angiotensin II antagonists for hypertension: are there differences in efficacy? Am J Hypertens. 2000;13:418–426.

    Article  PubMed  CAS  Google Scholar 

  17. Hedner T, Himmelmann A. The efficacy and tolerance of one or two daily doses of eprosartan in essential hypertension. Eprosartan multinational Study Group. J Hypertens. 1999;17:129–136.

    Article  PubMed  CAS  Google Scholar 

  18. Elliot WJ. Double-blind comparison of eprosartan and enalapril on cough and blood pressure in unselected hypertensive patients: Eprosartan Study Group. J Hum Hypertens. 1999;13:413–417.

    Article  CAS  Google Scholar 

  19. Argenziano L, Trimarco B. Effect of eprosartan and enalapril in the treatment of elderly hypertensive patients: subgroup analysis of a 26-week, doubleblind, multicenter study. Curr Med Res Opin. 1999;15:9–14.

    Article  PubMed  CAS  Google Scholar 

  20. Puig JG, Mateos F, Buño A, Ortega R, Rodriguez F, Dal-Ré R. Effect of eprosartan and losartan on uric acid metabolism in patients with essential hypertension. J Hypertens. 1999;17:1033–1039.

    Article  PubMed  CAS  Google Scholar 

  21. White WB, Anwar YA, Mansoor GA, et al. Evaluation of the 24-hour blood pressure effects of eprosartan in patients with systemic hypertension. Am J Hypertens. 2001;14:1248–1255.

    Article  PubMed  CAS  Google Scholar 

  22. Punzi HA, Punzi CF. Once-daily eprosartan mesylate in the treatment of elderly patients with isolated systolic hypertension: data from a 13-week double-blind, placebo-controlled, parallel, multicenter study. J Hum Hypertens. 2004;18:655–661.

    Article  PubMed  CAS  Google Scholar 

  23. Robins GW, Scott LJ. Eprosartan. A review of its use in the management of hypertension. Drugs. 2005;65:2355–2377.

    Article  PubMed  CAS  Google Scholar 

  24. Sega R. Efficacy and safety of eprosartan in severe hypertension. Blood Press. 1999;8:114–121.

    Article  PubMed  CAS  Google Scholar 

  25. Ruilope L, Jager B, Prichard B. Eprosartan vs. enalapril in elderly patients with hypertension: a double-blind, randomized trial. Blood Press. 2001;10:223–229.

    Article  PubMed  CAS  Google Scholar 

  26. Ohlstein EH, Brooks DP, Feuerstein GZ, Ruffolo RR. Inhibition of sympathetic outflow by the angiotensin II receptor antagonist eprosartan, but not by losartan, valsartan or irbesartan: relationship to differences in pre-junctional angiotensin II receptor blockade. Pharmacology. 1997;55:244–251.

    Article  PubMed  CAS  Google Scholar 

  27. Arosio E, De Marchi E, Prior M, Rigoni A, Lechi A. Haemodynamic effects of eprosartan and valsartan in hypertensive patients during isometric and mental stress. J Hypertens. 2005;23:1923–1927.

    Article  PubMed  CAS  Google Scholar 

  28. Sachse A, Verboom CN, Jäger B. Efficacy of eprosartan in combination with HCTZ in patients with essential hypertension. J Hum Hypertens. 2002;16:169–176.

    Article  PubMed  CAS  Google Scholar 

  29. Hernandez-Hernandez R, Sosa-Canache B, Velasco M, Armas-Hernandez MJ, Armas-Padilla MJ, Cammarata R. Angiotensin II receptor antagonists role in arterial hypertension. J Hum Hypertens. 2002;16(suppl. 1):93–99.

    Article  Google Scholar 

  30. Mancia G, Parati G. Ambulatory blood pressure monitoring and organ damage. Hypertension. 2000;36:894–900.

    PubMed  CAS  Google Scholar 

  31. Sega R, Corrao G, Bombelli M, et al. Blood pressure variability and organ damage in a general population. Results from the PAMELA study. Hypertension. 2002;39(part 2):710–714.

    Article  PubMed  CAS  Google Scholar 

  32. Inoue R, Ohkubo T, Kikuya M, et al. Stroke risk in systolic and combined systolic and diastolic hypertension determined using ambulatory blood pressure. The Ohasama Study. Am J Hypertens. 2007;20:1125–1131.

    Article  PubMed  Google Scholar 

  33. Chalmers J, MacMahon S, Mancia G, et al. 1999 World Health Organization-International Society of Hypertension Guidelines for the management of hypertension. Clin Exper Hypertens. 1999;21:1009–1060.

    Article  CAS  Google Scholar 

  34. Neutel JM, Kolloch RE, Plouin PF, Meinicke TW, Schumacher H; Study Group. Telmisartan vs losartan plus hydrochlorothiazide in the treatment of mild-to-moderate essential hypertension - a randomized ABPM study. J Hum Hypertens. 2003;17:569–575.

    Article  PubMed  CAS  Google Scholar 

  35. Smith DHG, Dubiel R, Jones M. Use of 24-hour ambulatory blood pressure monitoring to assess antihypertensive efficacy: a comparison of olmesartan medoxomil, losartan potassium, valsartan, and irbesartan. Am J Cardiovasc Drugs. 2005;5:41–50.

    Article  PubMed  CAS  Google Scholar 

  36. Lacourciere Y, Neutel JM, Schumacher H. Comparison of fixed-dose combinations of telmisartan/hydrochlorothiazide 40/12.5 mg and 80/12.5 mg and a fixed-dose combination of losartan/hydrochlorothiazide 50/12.5 mg in mild to moderate essential hypertension: pooled analysis of two multicenter, prospective, randomized, openlabel, blinded-endpoint (PROBE) trials. Clin Ther. 2005;27:1795–1805.

    Article  PubMed  CAS  Google Scholar 

  37. Parati G, Bosi S, Castellano M, et al. Guidelines for 24-h non invasive ambulatory blood pressure monitoring. Report from a working group of the Italian Society of Hypertension. High Blood Press. 1995;4:168–174.

    Google Scholar 

  38. Fogari R, Zoppi A, Mugellini A, et al. Comparative efficacy of losartan and valsartan in mild-tomoderate hypertension: results of 24-hour ambulatory blood pressure monitoring. Curr Ther Res. 1999;60:195–206.

    Article  CAS  Google Scholar 

  39. 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 Hypertension. 2007;25:1327–1336.

    Article  CAS  Google Scholar 

  40. Parati G, Omboni S, Rizzoni D, Agabiti-Rosei E, Mancia G. The smoothness index: a new reproducible and clinically relevant measure of the homogeneity of the blood pressure reduction with treatment for hypertension. J Hypertens. 1998;16:1685–1691.

    Article  PubMed  CAS  Google Scholar 

  41. Rizzoni D, Muiesan ML, Salvetti M, et al. The smoothness index, but not the trough-to-peak ratio predicts changes in carotid artery wall thickness during antihypertensive treatment. J Hypertens. 2001;19:703–711.

    Article  PubMed  CAS  Google Scholar 

  42. Meredith PA. FDA Guidelines on trough:peak ratios in the evaluation of anithypertensive agents. United States Food and Drug Administration. J Cardiovasc Pharmacol. 1994;5:26–30.

    Google Scholar 

  43. Greathouse M. Olmesartan medoxomil combined with hydrochlorothiazide for the treatment of hypertension. Vasc Health Risk Manag. 2006;2:401–409.

    Article  PubMed  CAS  Google Scholar 

  44. Neutel JM. The role of combination therapy in the management of hypertension. Nephrol Dial Transplant. 2006;21:1469–1474.

    Article  PubMed  Google Scholar 

  45. Struijker-Boudier HAJ, Ambrosioni E, Holzgreve H, et al. The need for combination anithypertensive therapy to reach target blood pressures: what has been learned from clinical practice and morbidity-mortality trials? Int J Clin Pract. 2007;61:1592–1602.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine 1, University of Bologna, Sant’Orsola Hospital, Bologna, Italy

    Ettore Ambrosioni

  2. Department of Clinical Medicine and Prevention, University of Milano-Bicocca, St. Gerardo Hospital, Milan, Italy

    Michele Bombelli & Giuseppe Mancia

  3. Dipartimento di Medicina Interna, Malattie Cardiovascolari e Nefrourologiche, Cattedra di Medicina Interna, European Society of Hypertension Centre of Excellence, Università di Palermo, Palermo, Italy

    Giovanni Cerasola & Giuseppe Mulè

  4. Atherosclerosis, Hypertension and Dyslipidemia Unit, G.d’Annunzio University of Chieti-Pescara, Chieti-Pescara, Italy

    Francesco Cipollone

  5. Department of Internal Medicine and Public Health, University of L’Aquila, Coppito (AQ), Italy

    Claudio Ferri

  6. Medical Department, Abbot, Via della Libertà, 30-10095, Grugliasco (Turin), Italy

    Irene Grazioli & Gabriella Melzi

  7. First Department of Internal Medicine, Venice City Hospital, Venice, Italy

    Cristiana Leprotti

  8. Department of Internal Medicine and Therapeutics, Centro per l’Ipertensione e Fisiopatologia Cardiovascolare, University of Pavia, Pavia, Italy

    Amedeo Mugellini

  9. Clinica Medica ‘A. Murri’, Department of Internal & Public Medicine, University Medical School of Bari, Bari, Italy

    Giuseppe Palasciano

  10. Department of Internal Medicine, University of Pisa, Pisa, Italy

    Antonio Salvetti

  11. Division of Internal Medicine, Department of Clinical Medicine & Cardiovascular Sciences, ‘Federico II’ University of Naples, Naples, Italy

    Bruno Trimarco

Authors
  1. Ettore Ambrosioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michele Bombelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giovanni Cerasola
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francesco Cipollone
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Claudio Ferri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Irene Grazioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cristiana Leprotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Giuseppe Mancia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gabriella Melzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Amedeo Mugellini
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Giuseppe Mulè
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Giuseppe Palasciano
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Antonio Salvetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Bruno Trimarco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriella Melzi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ambrosioni, E., Bombelli, M., Cerasola, G. et al. Ambulatory monitoring of systolic hypertension in the elderly: Eprosartan/hydrochlorothiazide compared with losartan/hydrochlorothiazide (INSIST trial). Adv Therapy 27, 365–380 (2010). https://doi.org/10.1007/s12325-010-0032-7

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-010-0032-7

Keywords

Search

Navigation