Skip to main content
SpringerLink
Log in

The Role of Irbesartan in the Treatment of Patients with Hypertension

A Comprehensive and Practical Review

  • Review Article
  • Published:
High Blood Pressure & Cardiovascular Prevention Aims and scope Submit manuscript

Abstract

Irbesartan is an orally active angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]) whose pharmacological profile differs significantly from those of many other compounds of the same class.

In particular, according to its pharmacokinetic and pharmacodynamic profile, irbesartan has a high bioavailability, a long duration of action and a small potential for pharmacological interactions due to the nature of the enzymatic pathway involved in its metabolic process. Morbidity data with irbesartan have been mainly accumulated in patients with renal impairment where the drug has demonstrated the most remarkable evidence of efficacy among the ARBs class, regardless of the stage of the renal disease (from early to late) and the length of the observational period. The efficacy of irbesartan has also been demonstrated in patients with left ventricular hypertrophy and congestive heart failure. The drug is indicated for the treatment of hypertension and renal impairment in patients with type 2 diabetes mellitus (T2D) and hypertension, and its tolerability and safety profile have been extensively investigated and reported to be similar to placebo.

From the pharmacoeconomic point of view, treating patients with T2D, hypertension and overt nephropathy using irbesartan was both a cost- and life-saving procedure compared with the use of amlodipine and standard antihypertensive treatment in an Italian setting.

The role of irbesartan in the management of hypertension with or without T2D and renal impairment is clearly recognized by national and international guidelines and largely acknowledged by the medical community according to the efficacy of the drug in the prevention of cardiovascular risk in addition to and beyond kidney prevention.

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

Fig. 1
Table I
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. McConnaughey MM, McConnaughey JS, Ingenito AJ. Practical considerations of the pharmacology of angiotensin receptor blockers. J Clin Pharmacol 1999; 39: 547–59.

    Article  PubMed  CAS  Google Scholar 

  2. Ruilope L. Human pharmacokinetic/pharmacodynamic profile of irbesartan: a new potent angiotensin II receptor antagonist. J Hypertens 1997; 15 Suppl. 7: s15–20.

    CAS  Google Scholar 

  3. Bristol Myers Squibb Company. Avapro (irbesartan) United States prescribing information. Princeton (NJ): Bristol Myers Squibb Company. Last text revision: 2005 Oct [online]. Available from URL: http://www.bms.com [Accessed 2006 Mar 31]

  4. Physicians Desk Reference Electronic Library website. Last text revision: 2005 Jul [online]. Available from URL: http://www.micromedex.com [Accessed 2006 Mar 6]

  5. Chando TJ, Everett DW, Kahle AD, et al. Biotransformation of irbesartan in man. Drug Metab Dispos 1998; 26 (5): 408–17.

    PubMed  CAS  Google Scholar 

  6. Vachharajani NN, Shyu WC, Mantha S, et al. Lack of effect of food on the oral bioavailability of irbesartan in healthy male volunteers. J Clin Pharmacol 1998; 38 (5): 433–6.

    Article  PubMed  CAS  Google Scholar 

  7. Croom KF, Curran MP, Goa KL, et al. Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy. Drugs 2004; 64: 999–1028.

    Article  PubMed  CAS  Google Scholar 

  8. Vachharajani NN, Shyu WC, Chando TJ, et al. Oral bioavailability and disposition characteristics of irbesartan, an angiotensin antagonist, in healthy volunteers. J Clin Pharmacol 1998; 38 (8): 702–7.

    Article  PubMed  CAS  Google Scholar 

  9. Markham A, Spencer C. Irbesartan: an updated review of its use in cardiovascular disorders. Drugs 2000; 59 (5): 1187–206.

    Article  PubMed  CAS  Google Scholar 

  10. Morsing P, Adler G, Brandt-Eliasson U, et al. Mechanistic differences of various AT1-receptor blockers in isolated vessels of different origin. Hypertension 1999; 33 (6): 1406–13.

    Article  PubMed  CAS  Google Scholar 

  11. Official drug review [online]. Available from URL: http://www.torrinomedica.it/farmaci/schedetecniche/Aprovel_300_Mg.asp [Accessed 2011 Jun]

  12. Marino MR, Langenbacher K, Ford NF, et al. Pharmacokinetics and pharmacodynamics of irbesartan in healthy subjects. J Clin Pharmacol 1998; 38: 246–55.

    Article  PubMed  CAS  Google Scholar 

  13. Sica DA, Marino MR, Hammett JL, et al. The pharmacokinetics of irbesartan in renal failure and maintenance hemodialysis. Clin Pharmacol Ther 1997; 62: 610–8.

    Article  PubMed  CAS  Google Scholar 

  14. Marino MR, Marino MR, Hammett JL, et al. Pharmacokinetics and pharmacodynamics of irbesartan in patients with hepatic cirrhosis. J Clin Pharmacol 1998; 38: 347–56.

    Article  PubMed  CAS  Google Scholar 

  15. Bramlage P, Durand-Zaleski I, Desai N, et al. The value of irbesartan in the management of hypertension. Expert Opin Pharmacother 2009; 10 (11): 1817–31.

    Article  PubMed  CAS  Google Scholar 

  16. Borghi C, Ertek S, Cicero AFG. Irbesartan: a review of its use alone and in combination with hydrochlorothiazide. Future Drugs 2006; 3 (69): 733–49.

    CAS  Google Scholar 

  17. Fogari R, Ambrosoli S, Corradi L, et al. 24-hour blood pressure control by once-daily administration of irbesartan assessed by ambulatory blood pressure monitoring. J Hypertens 1997; 15: 1511–8.

    Article  PubMed  CAS  Google Scholar 

  18. Pool JL, Guthrie RM, Littlejohn 3rd TW, et al. Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension. Am J Hypertens 1998; 11: 462–70.

    Article  PubMed  CAS  Google Scholar 

  19. Guthrie R, Saini R, Herman T, et al. Efficacy and tolerability of irbesartan, an angiotensin II receptor antagonist, in primary hypertension: a double-blind, placebo-controlled, dose-titration study. Clin Drug Invest 1998; 15: 217–27.

    Article  CAS  Google Scholar 

  20. Reeves RA, Lin CS, Kassler-Taub K, et al. Dose-related efficacy of irbesartan for hypertension: an integrated analysis. Hypertension 1998; 31: 1311–6.

    Article  PubMed  CAS  Google Scholar 

  21. Kassler-Taub K, Littlejohn T, Elliott W, et al. Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and losartan, in mild-to-moderate hypertension. Am J Hypertens 1998; 11: 445–53.

    Article  PubMed  CAS  Google Scholar 

  22. Oparil S, Guthrie R, Lewin AJ, et al. An elective titration study of the comparative effectiveness of two angiotensin II receptor blockers, irbesartan and losartan. Clin Ther 1998; 20: 398–409.

    Article  PubMed  CAS  Google Scholar 

  23. Mancia G, Korlipara K, van Rossum P, et al. An ambulatory blood pressure monitoring study of the comparative antihypertensive efficacy of two angiotensin II receptor antagonists, irbesartan and valsartan. Blood Press Monit 2002; 7: 1–8.

    Article  Google Scholar 

  24. Bobrie G, Delonca J, Moulin C, et al. on behalf of the Comparative Study of Efficacy of Irbesartan/HCTZ with Valsartan/HCTZ using Home Blood Pressure Monitoring in the TreAtment of Mild-to-Moderate Hypertension (COSIMA) Investigators. A home blood pressure monitoring study comparing the antihypertensive efficacy of two angiotensin II receptor antagonist fixed combinations. Am J Hypertens 2005; 18 (11): 1482–8.

    Article  PubMed  CAS  Google Scholar 

  25. Lewis EJ, Hunsicker LG, Clarke WR, et al., on behalf of the Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–60.

    Article  PubMed  CAS  Google Scholar 

  26. Brenner BM, Cooper ME, de Zeeuw D, et al., on behalf of the RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Eng J Med 2001; 345 (12): 861–9.

    Article  CAS  Google Scholar 

  27. Berl T, Hunsicker LG, Lewis JB, et al., on behalf of the Irbesartan Diabetic Nephropathy Trial, Collaborative Study Group. Cardiovascular outcomes in the irbesartan diabetic nephropathy trial of patients with type 2 diabetes and overt nephropathy. Ann Intern Med 2003; 138: 542–9.

    Article  PubMed  CAS  Google Scholar 

  28. Parving HH, Lehnert H, Bröchner-Mortensen J, et al., on behalf of the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345: 870–8.

    Article  PubMed  CAS  Google Scholar 

  29. Andersen S, Bröchner-Mortensen J, Parving HH, on behalf of the Irbesartan in Patients With Type 2 Diabetes and Microalbuminuria Study Group. Kidney function during and after withdrawal of long-term irbesartan treatment in patients with type 2 diabetes and microalbuminuria. Diabetes Care 2003; 26: 3296–302.

    Article  PubMed  Google Scholar 

  30. Viberti G, Wheeldon NM, on behalf of the MicroAlbuminuria Reduction With VALsartan (MARVAL) Study Investigators. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 2002; 106: 672–8.

    Article  PubMed  CAS  Google Scholar 

  31. Haller H, Ito S, Izzo Jr JL, et al., on behalf of the ROADMAP Trial Investigators. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med 2011 Mar 10; 364 (10): 907–17.

    Article  PubMed  CAS  Google Scholar 

  32. Bilous R, Chaturvedi N, Sjølie AK, et al. Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials. Ann Intern Med 2009; 151: 11–20.

    Article  PubMed  Google Scholar 

  33. Ghosh A. The metabolic syndrome: a definition dilemma. Cardiovasc J Africa 2011; 22(6): 296–792

    Google Scholar 

  34. National Cholesterol Education Program. Executive summary of the third report of the National Cholesterol Education Program (NCEP): expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001; 285: 2479–86.

    Google Scholar 

  35. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement (executive summary). Circulation 2005; 112:e285–90

    Article  Google Scholar 

  36. Sattar N, Gaw A, Scherbakova O, et al. Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation 2003; 108: 414–9.

    Article  PubMed  CAS  Google Scholar 

  37. Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001; 24: 683–9.

    Article  PubMed  CAS  Google Scholar 

  38. Mancia G, De Backer G, Dominiczak A, et al., Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 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: 1105–87.

    Article  PubMed  CAS  Google Scholar 

  39. Mancia G, Laurent S, Agabiti-Rosei E, et al., on behalf of the European Society of Hypertension. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens 2009; 27: 2121–58.

    Article  PubMed  CAS  Google Scholar 

  40. Eriksson JW, Jansson PA, Carlberg B, et al. Hydrochlorothiazide, but not candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation. Hypertension 2008; 52: 1030–7.

    Article  PubMed  CAS  Google Scholar 

  41. Dronavalli S, Bakris GL. Mechanistic insights into diuretic-induced insulin resistance. Hypertension 2008; 52: 1009–11.

    Article  PubMed  CAS  Google Scholar 

  42. Israili ZH, Lyoussi B, Hernandez-Hernandez R, et al. Metabolic syndrome: treatment of hypertensive patients. Am J Ther 2007; 14: 386–402.

    Article  PubMed  Google Scholar 

  43. Sowers JR, Neutel JM, Saunders E, et al. Antihypertensive efficacy of irbesartan/HCTZ in men and women with the metabolic syndrome and type 2 diabetes. J Clin Hypertens 2006; 8: 470–80.

    Article  CAS  Google Scholar 

  44. Parhofer KG, Münzel F, Krekler M. Effect of the angiotensin receptor blocker irbesartan on metabolic parameters in clinical practice: the DO-IT prospective observational study. Cardiovasc Diabetol 2007; 6: 36.

    Article  PubMed  CAS  Google Scholar 

  45. Baumhäkel M, Schlimmer N, Böhm M, on behalf of the DO-IT Investigators. Effect of irbesartan on erectile function in patients with hypertension and metabolic syndrome. Int J Impot Res 2008; 20 (5): 493–500.

    Article  PubMed  CAS  Google Scholar 

  46. Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet 2007; 369: 201–7.

    Article  PubMed  CAS  Google Scholar 

  47. Bakris GL, Stockert J, Molitch M, et al., on behalf of the STAR Investigators. Risk factor assessment for new onset diabetes: literature review. Diab Obes Metab 2009; 11: 177–87.

    Article  CAS  Google Scholar 

  48. McMurray JJ, Holman RR, Haffner SM, et al., on behalf of the NAVIGATOR Study Group. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med 2010; 362 (16): 1477–90.

    Article  PubMed  CAS  Google Scholar 

  49. Gerstein HC, Yusuf S, Bosch J, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006; 368: 1096–105.

    Article  PubMed  CAS  Google Scholar 

  50. Kintscher U, Foryst-Ludwig A, Unger T. Inhibiting angiotensin type 1 receptors as a target for diabetes. Expert Opin Ther Targets 2008; 12: 1257–63.

    Article  PubMed  CAS  Google Scholar 

  51. Takai S, Jin D, Miyazaki MJ. Irbesartan prevents metabolic syndrome in rats via activation of peroxisome proliferator-activated receptor γ. Pharmacol Sci 2011; 116 (3): 309–15.

    Article  CAS  Google Scholar 

  52. Kintscher U, Bramlage P, Paar WD, et al. Irbesartan for the treatment of hypertension in patients with the metabolic syndrome: a sub analysis of the Treat to Target post authorization survey — prospective observational, two armed study in 14,200 patients. Cardiovasc Diabetol 2007; 6: 12.

    Article  PubMed  CAS  Google Scholar 

  53. Sola S, Mir MQ, Cheema FA, et al. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study. Circulation 2005 Jan 25; 111 (3): 343–8.

    Article  PubMed  CAS  Google Scholar 

  54. Parhofer KG, Birkeland KI, DeFronzo R, et al. Irbesartan has no short-term effect on insulin resistance in hypertensive patients with additional cardiometabolic risk factors (i-RESPOND). Int J Clin Pract 2010 Jan; 64 (2): 160–8.

    Article  PubMed  CAS  Google Scholar 

  55. Russell JC, Kelly SE, Vine DF, et al. Irbesartan-mediated reduction of renal and cardiac damage in insulin resistant JCR: LA-cp rats. Br J Pharmacol 2009; 158 (6): 1588–96.

    Article  PubMed  CAS  Google Scholar 

  56. Malmqvist K, Kahan T, Edner M, et al. Regression of left ventricular hypertrophy in human hypertension with irbesartan. J Hypertens 2001; 19 (6): 1167–76.

    Article  PubMed  CAS  Google Scholar 

  57. Gaudio C, Ferri FM, Giovannini M, et al. Comparative effects of irbesartan versus amlodipine on left ventricular mass index in hypertensive patients with left ventricular hypertrophy. J Cardiovasc Pharmacol 2003; 42: 622–8.

    Article  PubMed  CAS  Google Scholar 

  58. Mörtsell D, Malmqvist K, Held C, et al. Irbesartan reduces common carotid artery intima-media thickness in hypertensive patients when compared with atenolol: the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) study. J Intern Med 2007 May; 261 (5): 472–9.

    Article  PubMed  CAS  Google Scholar 

  59. Yusuf S, Healey JS, Pogue J, et al., on behalf of the ACTIVE I Investigators. Irbesartan in patients with atrial fibrillation. N Engl J Med 2011; 364 (10): 928–38.

    Article  PubMed  CAS  Google Scholar 

  60. Lindenfeld J. Does irbesartan improve the risk of death or hospitalization for cardiovascular causes among patients with HF and PEF? Curr Cardiol Rep 2010;12(3): 193–5

    Article  PubMed  Google Scholar 

  61. Massie BM, Carson PE, McMurray JJ, et al. on behalf of the i-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008; 359 (23): 2456–67.

    Article  PubMed  CAS  Google Scholar 

  62. Yusuf S, Pfeffer MA, Swedberg K, et al., on behalf of the CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-preserved Trial. Lancet. 2003; 362: 777–81.

    Article  PubMed  CAS  Google Scholar 

  63. Cleland JG, Tendera M, Adamus J, et al., on behalf of the PEP-CHF Investigators. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J 2006; 27: 2338–45.

    Article  PubMed  CAS  Google Scholar 

  64. Solomon SD, Janardhanan R, Verma A, et al., on behalf of the Valsartan In Diastolic Dysfunction (VALIDD) Investigators. Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial. Lancet 2007; 369 (9579): 2079–87.

    Article  PubMed  CAS  Google Scholar 

  65. Dilaveris P, Giannopoulos G, Synetos A, et al. The role of renin angiotensin system blockade in the treatment of atrial fibrillation. Curr Drug Targets Cardiovasc Haematol Disord 2005; 5: 387–403.

    Article  PubMed  CAS  Google Scholar 

  66. Schneider MP, Hua TA, Böhm M, et al. Prevention of atrial fibrillation by renin-angiotensin system inhibition a meta-analysis. J Am Coll Cardiol 2010 May 25; 55 (21): 2299–307.

    Article  PubMed  Google Scholar 

  67. Zaman AG, Kearney MT, Schecter C, et al. Angiotensin-converting enzyme inhibitors as adjunctive therapy in patients with persistent atrial fibrillation. Am Heart J 2004; 147: 823–7.

    Article  PubMed  CAS  Google Scholar 

  68. Madrid AH, Bueno MG, Rebollo JM, et al. Use of irbesartan to maintain sinus rhythm in patients with long lasting FA: a randomized prospective study. Circulation 2002; 106: 331–6.

    Article  PubMed  CAS  Google Scholar 

  69. Madrid AH, Marín IM, Cervantes CE, et al. Prevention of recurrences in patients with lone atrial fibrillation: the dose-dependent effect of angiotensin II receptor blockers. J Renin Angiotensin Aldosterone Syst 2004; 5 (3): 114–20.

    Article  PubMed  CAS  Google Scholar 

  70. Julius S, Weber MA, Kjeldsen SE, et al. The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy. Hypertension 2006; 48 (3): 385–91.

    Article  PubMed  CAS  Google Scholar 

  71. Ducharme A, Swedberg K, Pfeffer MA, et al., on behalf of the CHARM Investigators. Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. Am Heart J 2006; 152 (1): 86–92.

    Article  PubMed  Google Scholar 

  72. Disertori M, Latini R, Barlera S, et al., on behalf of the GISSI-AF Investigators. Valsartan for prevention of recurrent atrial fibrillation. N Engl J Med 2009; 360 (16): 1606–17.

    Article  PubMed  Google Scholar 

  73. Simon TA, Gelarden RT, Freitag SA, et al. Safety of irbesartan in the treatment of mild to moderate systemic hypertension. Am J Cardiol 1998; 82 (2): 179–82.

    Article  PubMed  CAS  Google Scholar 

  74. Palmer AJ, Annemans L, Roze S, et al. Cost-effectiveness of irbesartan in hypertensive type 2 diabetics with nephropathy: an Italian perspective [in Italian]. Pharmacoecon Ital Res Articles 2005; 7 (1): 43–57.

    Article  Google Scholar 

  75. Ravera M, Ratto E, Vettoretti S, et al. Prevention and treatment of diabetic nephropathy: the program for irbesartan mortality and morbidity evaluation. J Am Soc Nephrol 2005; 16: s48–52.

    Article  PubMed  CAS  Google Scholar 

  76. American Diabetes Association. Position statement: diabetic nephropathy. Diabetes Care 2003; 26 Suppl. 1: s94–8.

    Google Scholar 

  77. American Diabetes Association. Position statement: standards of medical care in diabetes. Diabetes Care 2009; 32 Suppl. 1: S1–61.

    Google Scholar 

Download references

Acknowledgements

The authors have no conflicts of interest that are directly relevant to the content of this review. Professor Borghi has received payment for lectures from Sanofi Aventis, Novartis, Boehringer Ingelheim, MSD and Pfizer. Bristol-Myers Squibb provided bibliographic support during the preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Medicine, Aging and Clinical Nephrology, University of Bologna, Bologna, Italy

    Claudio Borghi & Arrigo F. G. Cicero

  2. U.O di Medicina Interna, Ospedale Policlinico S.Orsola-Malpighi, Via Albertoni 15, 40138, Bologna, Italy

    Claudio Borghi

Authors
  1. Claudio Borghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arrigo F. G. Cicero
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claudio Borghi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Borghi, C., Cicero, A.F.G. The Role of Irbesartan in the Treatment of Patients with Hypertension. High Blood Press Cardiovasc Prev 19, 19–31 (2012). https://doi.org/10.2165/11632100-000000000-00000

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11632100-000000000-00000

key words

Search

Navigation