September 29, 2020
Valentina Forni, Gregoire Wuerzner, Menno Pruijm, Michel Burnier
AUTHOR: Valentina Forni, Gregoire Wuerzner, Menno Pruijm, Michel Burnier
Service of Nephrology and Hypertension, Department of Medicine, Centre HospitalierUniversitaire Vaudois, Lausanne, Switzerland
Journal Source: https://www.ncbi.nlm.nih.gov/p...
Date Published: April 18, 2011
The renin-angiotensin-aldosterone system (RAAS) is one of the most complex and important systems in controlling the blood pressure and fluid balance in the body. Dysregulation of the RAAS plays an important role in the pathogenesis of cardiovascular and renal disorders such as hypertension, myocardial infarction, heart failure, and chronic kidney disease. Angiotensin receptor blockers (ARBs) have been available for management of hypertension.
Irbesartan is a well-established angiotensin receptor blocker, approved worldwide for the treatment of hypertension. It lowers blood pressure over 24 hours. The usual starting dosage is 150 mg once daily and can be uptitrated to 300 mg once daily. It is also approved for the treatment of nephropathy in patients with hypertension and type 2 diabetes mellitus. 300 mg once daily is the recommended maintenance dosage.
Angiotensin-receptor blockers (ARBs) is an effective antihypertensive agent with an impressive safety profile and placebo-like tolerability. It provides benefits beyond the reduction in blood pressure in relation to heart failure, type II diabetes and renal insufficiency.Irbesartan, an ARB is recognized by national and international guidelines management of hypertension with or without type 2 diabetes or renal disease.
To determine the pharmacokinetic and pharmacodynamics characteristic of ARBs which focuses on recent clinical evidences and studies about the therapeutic efficacy and tolerability of Irbesartan when used as an oral monotherapy or combination therapy in essential hypertension, diabetic nephropathy and cardiac disease.
Irbesartan in monotherapy is found to be very effective in lowering both systolic and diastolic blood pressure. It is effective in producing a sustained 24 hour blood pressure control. It’s effect on blood pressure manifest within 2 weeks starting treatment and achieved maximum reduction after 2-6 weeks. In cases if mild-to-moderate hypertension, it also showed equal efficacy but better tolerability compared with other major antihypertensive classes.
Another study showed results that Irbesartan does not also affect renal hemodynamics and renal salt handling when combined with COX-2 inhibitors. It is strictly contraindicated in the second and third trimester of pregnancy and during lactation and it has been found to induce renal vasodilatation without altering glomerular filtration rate, to improve endothelial function, and to reduce oxidative stress and inflammation in the kidney.
Irbesartan improved microalbuminuria also in a normotensive subgroup of diabetic patients with early stage microalbuminuric nephropathy and significantly reduced QT and corrected QT interval dispersion with a reduction in the risk of arrhythmias in cardiac disease. A dosage of 150-300 mg once daily was found to induce greater left ventricular mass index regression.
Irbesartan as monotherapy or as combination therapy with hydrocholorthiazide was associated with low discontinuation rates for adverse events and low incidences of serious adverse events. Persistence with a drug can be regarded as a good general indicator of the satisfaction of both patients and physicians with the efficacy and tolerability of the treatment.
Irbesartan is an effective antihypertensive drug in variety of mild – to – moderate hypertensive population.It is found to be effective on patients with diabetes, obesity, renal insufficiency and cardiovascular disease. Its action slows the progression of early stage and late stage renal disease in hypertensive patients with type 2 diabetes and reduces the risks of heart failure episodes.Treatment with Irbesartan in hypertensive patients with type 2 diabetes and nephropathy resulted in improved life expectancy and appeared to be cost-saving and scores well for patient acceptation and adherence rates.
Marvin Jino S. Bugna, MD
1. Probstfield JL, O’Brien KD. Progression of cardiovascular damage: The role of renin-angiotensin system blockade. Am J Cardiol. 2010;105:10A–20A.
2. Ribeiro AB. Angiotensin II antagonists – therapeutic benefits spanning the cardiovascular disease continuum from hypertension to heart failure and diabetic nephropathy. Curr Med Res Opin. 2006;22:1–16. 3. Grossman E, Messerli FH, Neutel JM. Angiotensin II receptor blockers: Equal or preferred substitutes for ACE inhibitors? Arch Intern Med. 2000;160:1905–1911. 4. Chan P, Tomlinson B, Huang TY, Ko JT, Lin TS, Lee YS. Double-blind comparison of losartan, lisinopril, and metolazone in elderly hypertensive patients with previous angiotensin-converting enzyme inhibitor-induced cough. J ClinPharmacol. 1997;37:253–257. 5. Burnier M. Medication adherence and persistence as the cornerstone of effective antihypertensive therapy. Am J Hypertens. 2006;19: 1190–1196. 6. Croom KF, Plosker GL. Irbesartan: A review of its use in hypertension and diabetic nephropathy. Drugs. 2008;68:1543–1569. 7. Herbert JM, Delisee C, Dol F, et al. Effect of SR47436, a novel angiotensin II AT1 receptor antagonist, on human vascular smooth muscle cells in vitro. Eur J Pharmacol. 1994;251:143–150.
8. Brunner HR. The new angiotensin II receptor antagonist, irbesartan: Pharmacokinetic and pharmacodynamic considerations. Am J
Hypertens. 1997;10:311S–317S. 9. Marino MR, Langenbacher K, Ford NF, Uderman HD. Pharmacokinetics and pharmacodynamics of irbesartan in healthy subjects. J Clin
10. Ruilope L. Human pharmacokinetic/pharmacodynamic profile of
irbesartan: A new potent angiotensin II receptor antagonist. J Hypertens Suppl. 1997;15:S15–S20.
11. Vachharajani NN, Shyu WC, Smith RA, Greene DS. The effects of age and gender on the pharmacokinetics of irbesartan. Br J ClinPharmacol. 1998;46:611–613.
12. Marino MR, Langenbacher KM, Raymond RH, Ford NF, Lasseter KC. Pharmacokinetics and pharmacodynamics of irbesartan in patients with hepatic cirrhosis. J ClinPharmacol. 1998;38:347–356.
13. Kostis JB, Vachharajani NN, Hadjilambris OW, Kollia GD, Palmisano M, Marino MR. The pharmacokinetics and pharmacodynamics of irbesartan in heart failure. J ClinPharmacol. 2001;41:935–942.
14. Sica DA, Marino MR, Hammett JL, Ferreira I, Gehr TW, Ford NF. The pharmacokinetics of irbesartan in renal failure and maintenance hemodialysis. ClinPharmacolTher. 1997;62:610–618.
15. Croom KF, Curran MP, Goa KL, Perry CM. Irbesartan: A review of its use in hypertension and in the management of diabetic nephropathy. Drugs. 2004;64:999–1028.
16. Marino MR, Vachharajani NN. Drug interactions with irbesartan. ClinPharmacokinet. 2001;40:605–614.
17. Kovacs SJ, Wilton J, Blum R. Steady state (SS) pharmacokinetics (PK) of irbesartan alone and in combination with fluconazole (F). ClinPharmacolTher. 1999;65:Abstr 132.
18. Kistler T, Ambuhl PM. Renal safety of combined cyclooxygenase 2 (COX-2) inhibitor and angiotensin II receptor blocker administration in mild volume depletion. Swiss Med Wkly. 2001;131:193–198.
19. Hong X, Zhang S, Mao G, et al. CYP2C9*3 allelic variant is associated with metabolism of irbesartan in Chinese population. Eur J ClinPharmacol. 2005;61:627–634.
20. Lacourciere Y. A multicenter, randomized, double-blind study of the antihypertensive efficacy and tolerability of irbesartan in patients aged . or = 65 years with mild to moderate hypertension. ClinTher. 2000;22:1213–1224.
21. Mimran A, Ruilope L, Kerwin L, et al. A randomised, double-blind comparison of the angiotensin II receptor antagonist, irbesartan, with the full dose range of enalapril for the treatment of mild-to-moderate hypertension. J Hum Hypertens. 1998;12:203–208.
22. Coca A, Calvo C, Garcia-Puig J, et al. A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: The MAPAVEL Study (MonitorizacionAmbulatoriaPresion Arterial APROVEL). ClinTher. 2002;24:126–138.
23. Mancia G, Korlipara K, van RP, Villa G, Silvert B. An ambulatory blood pressure monitoring study of the comparative antihypertensive efficacy of two angiotensin II receptor antagonists, irbesartan and valsartan. Blood Press Monit. 2002;7:135–142.
24. Kassler-Taub K, Littlejohn T, Elliott W, Ruddy T, Adler E. Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and losartan in mild-to-moderate hypertension. Irbesartan/Losartan Study Investigators. Am J Hypertens. 1998;11:445–453.
25. 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. Irbesartan/Losartan Study Investigators. ClinTher. 1998;20:398–409.
26. Neutel JM, Germino FW, Smith D. Comparison of monotherapy with irbesartan 150 mg or amlodipine 5 mg for treatment of mild-to-moderate hypertension. J Renin Angiotensin Aldosterone Syst. 2005;6:84–89.
27. Chiou KR, Chen CH, Ding PY, et al. Randomized, double-blind comp
28. Stumpe KO, Haworth D, Hoglund C, et al. Comparison of the
angiotensin II receptor antagonist irbesartan with atenolol for treatment of hypertension. Blood Press. 1998;7:31–37.
29. 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. Irbesartan Multicenter Investigators’ Group. J Hypertens. 1997;15:1511–1518.
30. Pool JL, Guthrie RM, Littlejohn TW III, et al. Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension. Am J Hypertens. 1998;11:462–470.
31. Reeves RA, Lin CS, Kassler-Taub K, Pouleur H. Dose-related efficacy of irbesartan for hypertension: An integrated analysis. Hypertension. 1998;31:1311–1316.
32. Howe P, Phillips P, Saini R, Kassler-Taub K. The antihypertensive efficacy of the combination of irbesartan and hydrochlorothiazide assessed by 24-hour ambulatory blood pressure monitoring. Irbesartan Multicenter Study Group. ClinExpHypertens. 1999;21:1373–1396.
33. Rosenstock J, Rossi L, Lin CS, MacNeil D, Osbakken M. The effects of irbesartan added to hydrochlorothiazide for the treatment of hypertension in patients non-responsive to hydrochlorothiazide alone. J Clin Pharm Ther. 1998;23:433–440.
34. Kochar M, Guthrie R, Triscari J, Kassler-Taub K, Reeves RA. Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension. Am J Hypertens. 1999;12:797–805.
35. Kawano Y, Sato Y, Yoshinaga K. A randomized trial of the effect of an angiotensin II receptor blocker SR47436 (irbesartan) on 24-hour blood pressure in patients with essential hypertension. Hypertens Res. 2008;31:1753–1763.
36. Gradman AH, Schmieder RE, Lins RL, Nussberger J, Chiang Y,
Bedigian MP. Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation. 2005;111:1012–1018.
37. Larochelle P, Flack JM, Marbury TC, Sareli P, Krieger EM, Reeves RA. Effects and tolerability of irbesartan versus enalapril in patients with severe hypertension. Irbesartan Multicenter Investigators. Am J Cardiol. 1997;80:1613–1615.
38. Derosa G, Cicero AF, Gaddi A, Mugellini A, Ciccarelli L, Fogari R. Effects of doxazosin and irbesartan on blood pressure and metabolic control in patients with type 2 diabetes and hypertension. J Cardiovasc Pharmacol. 2005;45:599–604.
39. 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 ClinHypertens (Greenwich). 2001;3: 283–291, 318.
40. Smith DH, Dubiel R, Jones M. Use of 24-hour ambulatory blood pressure monitoring to assess antihypertensive efficacy: A comparison of olmesartanmedoxomil, losartan potassium, valsartan, and irbesartan. Am J Cardiovasc Drugs. 2005;5:41–50.
41. 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.
42. Polonia J, Diogo D, Caupers P, Damasceno A. Influence of two doses of irbesartan on non-dipper circadian blood pressure rhythm in salt-sensitive black hypertensives under high salt diet. J Cardiovasc Pharmacol. 2003;42:98–104.
43. Weber M, Saini R, Kassler-Taub K. Irbesartan combined with low-dose hydrochlorothiazide for mild-to-moderate hypertension. J Hypertens. 1998;Suppl 2:Abstr 129.
44. Weir MR, Tolchin N, Toth P. Addition of hydrochlorothiazide to irbesartan produces further dose-related reduction in blood pressure within two weeks. Hypertension. 1998;Suppl 2:130.
45. Hunyady L, Catt KJ. Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II. Mol Endocrinol. 2006;20:953–970.
46. Hirata Y, Nagata D, Suzuki E, Nishimatsu H, Suzuki J, Nagai R. Diagnosis and treatment of endothelial dysfunction in cardiovascular disease. Int Heart J. 2010;51:1–6.
47. Derosa G, AT Salvadeo S. Endothelial function, blood pressure control, and risk modification: Impact of irbesartan alone or in combination. IBPC. May 18, 2010.
48. Ravera M, Ratto E, Vettoretti S, Parodi D, Deferrari G. Prevention and treatment of diabetic nephropathy: The program for irbesartan mortality and morbidity evaluation. J Am SocNephrol. 2005; 16 Suppl1:S48–S52.
49. Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345:870–878.
50. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–860.
51. Pohl MA, Blumenthal S, Cordonnier DJ, et al. Independent and additive impact of blood pressure control and angiotensin II receptor blockade on renal outcomes in the irbesartan diabetic nephropathy trial: Clinical implications and limitations. J Am SocNephrol. 2005;16:3027–3037.
52. Sasso FC, Carbonara O, Persico M, et al. Irbesartan reduces the albumin excretion rate in microalbuminuric type 2 diabetic patients independently of hypertension: A randomized double-blind placebo-controlled crossover study. Diabetes Care. 2002;25:1909–1913.
53. Burnier M, Hagman M, Nussberger J, et al. Short-term and sustained renal effects of angiotensin II receptor blockade in healthy subjects. Hypertension. 1995;25:602–609.
54. Schmitt F, Martinez F, Brillet G, et al. Acute renal effects of AT1receptor blockade after exogenous angiotensin II infusion in healthy subjects. J Cardiovasc Pharmacol. 1998;31:314–321.
55. Pechere-Bertschi A, Nussberger J, Decosterd L, et al. Renal response to the angiotensin II receptor subtype 1 antagonist irbesartan versus enalapril in hypertensive patients. J Hypertens. 1998;16:385–393.
56. Persson F, Rossing P, Hovind P, et al. Irbesartan treatment reduces biomarkers of inflammatory activity in patients with type 2
diabetes and microalbuminuria: An IRMA 2 substudy. Diabetes. 2006;55:3550–3555.
57. Ceriello A, Assaloni R, Da RR, et al. Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients.
58. 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;111:343–348.
59. Bonnet F, Cooper ME, Kawachi H, Allen TJ, Boner G, Cao Z. Irbesartan normalises the deficiency in glomerular nephrin expression in a model of diabetes and hypertension. Diabetologia. 2001;44:874–877.
60. Bakris GL, Ruilope L, Locatelli F, et al. Treatment of microalbuminuria in hypertensive subjects with elevated cardiovascular risk: Results of the IMPROVE trial. Kidney Int. 2007;72:879–885.
61. 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;42:622–628.
62. Malmqvist K, Kahan T, Edner M, et al. Regression of left ventricular hypertrophy in human hypertension with irbesartan. J Hypertens. 2001;19:1167–1176.
63. Malmqvist K, Kahan T, Edner M, Bergfeldt L. Comparison of actions of irbesartan versus atenolol on cardiac repolarization in hypertensive left ventricular hypertrophy: Results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation Versus Atenolol (SILVHIA). Am J Cardiol. 2002;90:1107–1112.
64. Muller-Brunotte R, Edner M, Malmqvist K, Kahan T. Irbesartan and atenolol improve diastolic function in patients with hypertensive left ventricular hypertrophy. J Hypertens. 2005;23:633–640.
65. Berl T, Hunsicker LG, Lewis JB, et al. Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy. Ann Intern Med. 2003;138:542–549.arison of irbesartan and enalapril for treatment of mild to moderate hypertension. Zhonghua Yi XueZaZhi (Taipei). 2000;63:368–376.
66. Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359:2456–2467.
67. Madrid AH, Bueno MG, Rebollo JM, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: A prospective and randomized study. Circulation. 2002;106:331–336.
68. Ji Q, Mei Y, Wang X, et al. Combination of irbesartan and amiodarone to maintain sinus rhythm in patients with persistent atrial fibrillation after rheumatic valve replacement. Circ J. 2010;74:1873–1879.
69. Yusuf S. ACTIVE-I: Irbesartan linked with reduced HF complications, embolic events in patients with AF. Presented at the European Society of Cardiology Congress, Barcelona, Spain; August 29–September 29, 2009.
70. Jones JK, Gorkin L, Lian JF, Staffa JA, Fletcher AP. Discontinuation of and changes in treatment after start of new courses of antihypertensive drugs: A study of a United Kingdom population. BMJ. 1995;311:293–295.
71. Caro JJ, Speckman JL, Salas M, Raggio G, Jackson JD. Effect of initial drug choice on persistence with antihypertensive therapy: The importance of actual practice data. CMAJ. 1999;160:41–46.
72. Marentette MA, Gerth WC, Billings DK, Zarnke KB. Antihypertensive persistence and drug class. Can J Cardiol. 2002;18:649–656.
73. Degli EE, Sturani A, Di MM, et al. Long-term persistence with antihypertensive drugs in new patients. J Hum Hypertens. 2002;16:439–444.
74. Hasford J, Mimran A, Simons WR. A population-based European cohort study of persistence in newly diagnosed hypertensive patients. J Hum Hypertens. 2002;16:569–575.
75. Simon TA, Gelarden RT, Freitag SA, Kassler-Taub KB, Davies R. Safety of irbesartan in the treatment of mild to moderate systemic hypertension. Am J Cardiol. 1998;82:179–182.
76. Man in’t Veld AJ. Clinical overview of irbesartan: Expanding the therapeutic window in hypertension. J Hypertens Suppl. 1997;15:S27–S33.
77. Burnier M, Hess B, Greminger P, Waeber B. Determinants of persistence in hypertensive patients treated with irbesartan: Results of a postmarketing survey. BMC Cardiovasc Disord. 2005;5:13.
78. Littlejohn T III, Saini R, Kassler-Taub K, Chrysant SG, Marbury T. Long-term safety and antihypertensive efficacy of irbesartan: Pooled results of five open-label studies. ClinExpHypertens. 1999;21: 1273–1295.
79. Raskin P, Guthrie R, Flack J, Reeves R, Saini R. The long-term antihypertensive activity and tolerability of irbesartanwith hydrochlorothiazide. J Hum Hypertens. 1999;13:683–687.
80. Franklin SS, Neutel JM. Efficacy and safety of irbesartan/HCTZ in severe hypertension according to cardiometabolic factors. J ClinHypertens (Greenwich). 2010;12:487–494.
81. Kum LC, Yip GW, Lee PW, et al. Comparison of angiotensin-converting enzyme inhibitor alone and in combination with irbesartan for the treatment of heart failure. Int J Cardiol. 2008;125:16–21.
82. Rodby RA, Chiou CF, Borenstein J, et al. The cost-effectiveness of irbesartan in the treatment of hypertensive patients with type 2 diabetic nephropathy. ClinTher. 2003;25:2102–2119.
83. Coyle D, Rodby RA. Economic evaluation of the use of irbesartan and amlodipine in the treatment of diabetic nephropathy in patients with hypertension in Canada. Can J Cardiol. 2004;20:71–79.
84. Palmer AJ, Annemans L, Roze S, Lamotte M, Rodby RA, Cordonnier DJ. An economic evaluation of irbesartan in the treatment of patients with type 2 diabetes, hypertension and nephropathy: Cost-effectiveness of Irbesartan in Diabetic Nephropathy Trial (IDNT) in the Belgian and French settings. Nephrol Dial Transplant. 2003;18:2059–2066.
85. Palmer AJ, Annemans L, Roze S. Cost-effectiveness analysis of irbesartan in patients with type 2 diabetes, hypertension and nephropathy: The Italian perspective. Pharmaeconomics. 2005;7:43–57.
86. Palmer AJ, Annemans L, Roze S, et al. Irbesartan is projected to be cost and life saving in a Spanish setting for treatment of patients with type 2 diabetes, hypertension, and microalbuminuria. Kidney Int Suppl. 2005;93:S52–S54.
87. Palmer AJ, Annemans L, Roze S, Lamotte M, Rodby RA, Bilous RW. An economic evaluation of the Irbesartan in Diabetic Nephropathy Trial (IDNT) in a UK setting. J Hum Hypertens. 2004;18:733–738.
88. Palmer AJ, Annemans L, Roze S, et al. Cost-effectiveness of early irbesartan treatment versus control (standard antihypertensive medications excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) or late irbesartan treatment in patients with type 2 diabetes, hypertension, and renal disease. Diabetes Care. 2004;27:1897–1903.
89. [email protected] [homepage on the Internet]. US Food and Drug Administration. 2011. [updated 2011 April 5]. Available from: http://www. accessdata.fda.gov/scripts/cder/drugsatfda/. Accessed April 6, 2011.
90. Swiss Compendium. [on the Internet]. 2010. http://www.kompendium. ch. Accessed March 30, 2011.
91. Yoshinaga K. A phase III clinical study of irbesartan, an angiotensin II receptor antagonist, in patients with essential hypertension: A doubleblind, intergroup, comparative trial using losartan potassium as the comparator. Rinsholyaku. 2008;24:543–573. Japanese.