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Drugs

, Volume 64, Issue 9, pp 999–1028 | Cite as

Irbesartan

A Review of its Use in Hypertension and in the Management of Diabetic Nephropathy
  • Katherine F. Croom
  • Monique P. Curran
  • Karen L. Goa
  • Caroline M. Perry
Adis Drug Evaluation

Summary

Abstract

Irbesartan (Avapro®, Aprovel®) is a potent and selective angiotensin II subtype 1 receptor antagonist indicated for use in patients with hypertension, including those with type 2 diabetes mellitus and nephropathy.

Once-daily administration of irbesartan provided 24-hour control of blood pressure (BP). In patients with mild-to-moderate hypertension irbesartan was as effective as enalapril, atenolol and amlodipine, and more effective than valsartan in terms of absolute reduction in BP and response rates. Irbesartan produced a greater reduction in diastolic BP at trough than once-daily losartan, but had a smaller effect than olmesartan; the reduction in systolic BP achieved with irbesartan was similar or greater than that with losartan and similar to that seen with olmesartan. The combination of irbesartan with hydrochlorothiazide produced additive effects on BP reduction. Irbesartan also induced regression of left ventricular mass in patients with hypertension and left ventricular hypertrophy.

In two large studies (IRbesartan MicroAlbuminuria type 2 diabetes mellitus in hypertensive patients [IRMA 2] and the Irbesartan Diabetic Nephropathy Trial [IDNT]) irbesartan exerted a renoprotective effect in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy. The renoprotective effect was at least partly independent of the BP-lowering effect. In the IRMA 2 trial, the proportion of patients progressing to overt nephropathy was significantly lower for recipients of irbesartan 300mg once daily than placebo. In patients with overt nephropathy in the IDNT, irbesartan 300mg once daily provided significantly greater renoprotection than amlodipine 10mg once daily or placebo. The relative risk of doubling of serum creatinine was significantly lower with irbesartan than amlodipine or placebo.

Irbesartan is well tolerated in hypertensive patients, including those with type 2 diabetes and incipient or overt nephropathy. The overall incidence of adverse events with irbesartan was similar to that with placebo. Irbesartan was associated with a lower incidence of cough than enalapril and was not associated with ankle oedema or with any clinically significant drug interactions.

In conclusion, irbesartan is a well tolerated and effective antihypertensive agent. It also slows the progression of renal disease in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy. Thus, irbesartan is a valuable agent in the management of patients with these indications.

Pharmacodynamic Properties

Irbesartan selectively binds to the angiotensin II receptor subtype 1 (AT1), inhibiting the activity of angiotensin II. Studies in normotensive volunteers indicate that irbesartan exerts a long-lasting inhibitory effect on the pressor response to exogenous angiotensin II. Irbesartan 5–300mg induced elevations in plasma renin activity and angiotensin II levels in volunteers with or without renal failure. In healthy volunteers, the AT1 blockade induced by irbesartan was generally significantly greater and of longer duration than that induced by losartan and valsartan. While irbesartan and candesartan demonstrated a similar extent of AT1 antagonistic activity in vivo, ex vivo/in vitro studies suggested higher antagonistic activity for irbesartan. A greater reduction in aldosterone levels and a greater increase in plasma renin activity occurred with irbesartan than with candesartan.

Systolic and diastolic blood pressure (BP) did not change significantly after single doses of irbesartan 5–300mg in salt-replete normotensive volunteers, but decreased following single doses of irbesartan 10–100mg in salt-depleted volunteers. Heart rate was unaltered.

In healthy volunteers and hypertensive patients, irbesartan 50mg and 100mg, respectively, increased renal blood flow and decreased renal vascular resistance without affecting the glomerular filtration rate. Irbesartan 50mg increased sodium excretion in normotensive volunteers, without altering potassium or uric acid excretion.

Pharmacokinetic Properties

The mean bioavailability of irbesartan is approximately 60–80% after oral administration and is not affected by food. After administration of single or multiple doses of irbesartan 150–300mg, maximum plasma drug concentrations (Cmax) were achieved within 1.5–2 hours. Values for Cmax and area under the concentration-time curve (AUC) are dose-related within this range and values are similar after single or multiple doses. Irbesartan is ≥90% bound to plasma proteins and has a steady-state volume of distribution of 53–93L.

The primary metabolic fate of irbesartan is oxidation via cytochrome P450 (CYP) isoform 2C9. Metabolism by CYP3A4 is negligible. The pharmacological activity of metabolites is minimal. After oral administration to healthy volunteers <10% and 30% of the parent drug was recovered in urine and faeces, respectively. Total plasma clearance of irbesartan was approximately 9–11 L/h, of which approximately 0.18 L/h was renal clearance. The elimination half-life of multiple doses of irbesartan 150 or 300mg was 11 hours.

No differences were noted in the pharmacokinetic properties of irbesartan between healthy men and women, but the AUC and Cmax were higher in elderly than younger volunteers. The pharmacokinetic parameters of irbesartan are not significantly altered by mild-to-moderate or severe renal impairment, mild-to-moderate hepatic impairment or heart failure.

No significant and clinically relevant drug interactions have been identified between irbesartan and hydrochlorothiazide, nifedipine, simvastatin, tolbutamide, warfarin, magnesium and aluminium hydroxides or digoxin. Fluconazole increased the irbesartan Cmax and AUC by 19% and 63%.

Therapeutic Efficacy in Hypertension

Monotherapy with irbesartan 150–300mg once daily was effective at reducing BP in patients with hypertension in double-blind, placebo- or active-controlled studies, leading to placebo-subtracted reductions in trough seated BP of approximately 8–10/5-6mm Hg. Reductions in BP were maintained over a 24-hour period with once-daily dosing. Irbesartan reduced BP by 11–19/7–13mm Hg in active-controlled clinical trials compared with reductions of 8–18/5–14mm Hg with the comparator drugs. Response rates with irbesartan were 36–72% compared with 43–68% for comparators.

Irbesartan 150mg once daily produced significantly greater reductions in diastolic and systolic BP and higher response and normalisation rates than valsartan 80mg once daily in the only study involving both these agents to include a statistical comparison. Reductions in diastolic BP with irbesartan 150–300mg once daily were greater than with losartan 50–100mg once daily, although the effect on systolic BP was significantly greater for irbesartan in only 1 of 2 studies, and there were no significant differences in response or normalisation rates between the drugs. Irbesartan 150mg once daily reduced diastolic BP to a lesser extent than olmesartan 20mg once daily, but produced similar changes in systolic BP and mean 24-hour ambulatory BP to olmesartan.

Several trials have shown irbesartan to be as effective as enalapril 10–20mg once daily in patients with mild-to-moderate hypertension, including in patients aged ≥65 years. Single studies have shown irbesartan 75–150mg once daily to produce similar decreases in BP to atenolol 50–100mg once daily, and irbesartan 150mg once daily to be as effective as amlodipine 5mg once daily.

The combination of irbesartan 75–300mg once daily with hydrochlorothiazide 12.5–25mg once daily produced additive BP-lowering effects in patients with mild-to-moderate hypertension. Irbesartan 150mg combined with hydrochlorothiazide 12.5mg (both once daily) produced reductions in BP of 4–7/2–4mm Hg additional to those with the individual components. The combination reduced BP in patients whose BP was unresponsive to monotherapy with irbesartan or hydrochlorothiazide.

Irbesartan induced regression of left ventricular mass in patients with left ventricular hypertrophy in several trials. The reduction in left ventricular mass was significantly greater with irbesartan than with amlodipine or atenolol, despite reductions in BP being similar for irbesartan and the comparators.

Therapeutic Efficacy in Hypertensive Patients with Type 2 Diabetes Mellitus and Nephropathy

Data from two large randomised, double-blind, placebo-controlled studies [Irbesartan Microalbuminuria Type 2 Diabetes Mellitus in hypertensive patients (IRMA 2) and the Irbesartan Diabetic Nephropathy Trial (IDNT)] showed that irbesartan slowed the development of overt nephropathy and the progression of renal disease in hypertensive patients with type 2 diabetes, and suggested that the renoprotective effect of irbesartan is at least in part independent of its BP-lowering effect.

In the IRMA 2 trial in patients with microalbuminuria (20–200 μg/min) and normal kidney function, overt nephropathy developed in 5% of irbesartan 300mg once daily recipients (p < 0.001 vs placebo), 10% of irbesartan 150mg once daily recipients (not significant) and 15% of placebo recipients. The hazard ratio for diabetic nephropathy was 0.3 in recipients of irbesartan 300mg once daily but did not achieve statistical significance in recipients of irbesartan 150mg once daily. Normoalbuminuria was restored in significantly more patients receiving irbesartan 300mg, but not 150mg, once daily compared with placebo. The renoprotective effect of irbesartan 300mg once daily was sustained in patients for whom antihypertensive medication was withdrawn for 1 month after completing 2 years of treatment.

The average trough systolic but not diastolic BP was significantly lower for the combined irbesartan groups than placebo (by l–3mm Hg). Reductions in ambulatory BP, measured in a subset of patients, were similar between groups.

In patients with more advanced renal disease, including proteinuria and elevated serum creatinine levels (IDNT), the relative risk of reaching the primary endpoint (a composite measure of doubling of the serum creatinine level, end-stage renal disease [ESRD] or death) was significantly lower in recipients of irbesartan 300mg once daily than placebo (by 20%) and amlodipine 10mg once daily (by 23%). The relative risk of doubling of serum creatinine levels and the rate at which serum creatinine levels increased were significantly lower in patients receiving irbesartan than placebo or amlodipine recipients. The relative risk of progression to ESRD alone was 23% lower in irbesartan recipients than in placebo or amlodipine recipients (not significant). The mean arterial BP in irbesartan recipients was not significantly different to that in amlodipine recipients.

Simulations of the long-term cost consequences of treatment with irbesartan, based on the outcomes of the IDNT, predicted that compared with amlodipine over a 25-year (lifetime) horizon irbesartan would be associated with an increase in life expectancy of 0.34–0.71 years and per-patient cost savings of €21 163-27 044 in the Belgian or French settings (year of costing 2002), $US26 290 in the US (year of costing 2000) and $Can 19 976 in Canada (year of costing 2001).

Tolerabilitv

There was no clinically relevant difference between irbesartan ≤900mg/day and placebo in the overall incidence of adverse drug events (21% vs 20%) in a pooled analysis of nine placebo-controlled trials. The incidence of withdrawal because of adverse events was 3.3% in irbesartan recipients and 4.5% in placebo recipients. Musculoskeletal trauma was the only adverse event to occur significantly more requently in recipients of irbesartan than placebo (1.9% vs 0.5%, p < 0.05).

Analysis of tolerability data from five nonblind trials (mean duration 276 days) involving 1006 patients with hypertension indicated that irbesartan monotherapy (≤300mg once daily) was well tolerated. In this analysis, the incidence of adverse drug experiences was 20% in recipients of irbesartan monotherapy, with 6% of recipients of irbesartan monotherapy discontinuing because of adverse events.

The overall incidence of adverse events with irbesartan was similar to that of most comparator agents. However, irbesartan was associated with a significantly lower incidence of cough than enalapril and was not associated with ankle oedema. The combination of irbesartan and hydrochlorothiazide was also well tolerated in patients with hypertension, with the overall incidence of adverse events being similar to that for placebo.

In the IRMA 2 trial, serious adverse events occurred in fewer irbesartan than placebo recipients (15% vs 23%). In the IDNT, the rate of adverse events per 1000 treatment days was significantly lower in recipients of irbesartan than placebo or amlodipine. The number of patients experiencing at least one serious adverse event did not differ significantly between the treatment groups. Significantly more irbesartan patients (1.9%) withdrew because of hyperkalaemia than amlodipine (0.5%) or placebo (0.4%) recipients. Patients treated with irbesartan reported more orthostatic symptoms than those receiving placebo.

Dosaae and Administration

Irbesartan is approved for the treatment of hypertension in many countries worldwide. In a number of countries, including the US, Canada, Australia and in Europe, it has also been approved for the treatment of nephropathy in patients with type 2 diabetes and hypertension.

Irbesartan may be used alone or in combination with other antihypertensive agents. The usual starting dosage is 150mg administered once daily, and the maximum recommended dosage for both indications is 300mg once daily, which is also the recommended maintenance dosage for patients with diabetic nephropathy. Irbesartan may be administered with or without food. No dosage adjustments are necessary in patients with hepatic or renal impairment. Dosage adjustments are not usually necessary in elderly patients, but consideration may be given to starting treatment at 75mg once daily in those aged >75 years. Irbesartan should not be administered during the second and third trimesters of pregnancy.

Keywords

Losartan Amlodipine Hydrochlorothiazide Valsartan Irbesartan 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Gillis JC, Markham A. Irbesartan: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in the management of hypertension. Drugs 1997 Dec; 54(6): 885–902PubMedCrossRefGoogle Scholar
  2. 2.
    Markham A, Spencer CM, Jarvis B. Irbesartan: an update of its use in cardiovascular disorders. Drugs 2000 May; 59(5): 1187–206PubMedCrossRefGoogle Scholar
  3. 3.
    Burnier M. Angiotensin II type 1 receptor blockers. Circulation 2001 Feb 13; 103(6): 904–12PubMedCrossRefGoogle Scholar
  4. 4.
    Ellis ML, Patterson JH. A new class of antihypertensive therapy: angiotensin II receptor antagonists. Pharmacotherapy1996 Sep–Oct; 16(5): 849–60PubMedGoogle Scholar
  5. 5.
    White M, Racine N, Ducharme A, et al. Therapeutic potential of angiotensin II receptor antagonists. Expert Opin Invest Drugs 2001 Sep; 10(9): 1687–701CrossRefGoogle Scholar
  6. 6.
    Rodgers JE, Patterson JH. Angiotensin II-receptor blockers: Clinical relevance and therapeutic role [published erratum appears in Am J Health Syst Pharm 2001 Sep 1; 58 (17): 1168]. Am J Health Syst Pharm 2001 Apr; 58(8): 671–83PubMedGoogle Scholar
  7. 7.
    Belz GG, Butzer R, Kober S, et al. Time course and extent of angiotensin II antagonism after irbesartan, losartan, and valsartan in humans assessed by angiotensin II dose response and radioligand receptor assay. Clin Pharmacol Ther 1999 Oct; 66(4): 367–73PubMedCrossRefGoogle Scholar
  8. 8.
    Mazzolai L, Maillard M, Rossat J, et al. Angiotensin II receptor blockade in normotensive subjects: a direct comparison of three AT1 receptor antagonists. Hypertension 1999 Mar; 33(3): 850–5PubMedCrossRefGoogle Scholar
  9. 9.
    Ribstein J, Picard A, Armagnac C, et al. Inhibition of the acute effects of angiotensin II by the receptor antagonist irbesartan in normotensive men. J Cardiovasc Pharmacol 2001 Apr; 37(4): 449–60PubMedCrossRefGoogle Scholar
  10. 10.
    Burnier M, Hagman M, Nussberger J, et al. Short-term and sustained renal effects of angiotensin II receptor blockade in healthy subjects. Hypertension 1995 Apr; 25 (4 Pt 1): 602–9PubMedCrossRefGoogle Scholar
  11. 11.
    Schmitt F, Martinez F, Brillet G, et al. Acute renal effects of AT1-receptor blockade after exogenous angiotensin II infusion in healthy subjects. J Cardiovasc Pharmacol 1998 Feb; 31(2): 314–21PubMedCrossRefGoogle Scholar
  12. 12.
    Marino MR, Langenbacher K, Ford NF, et al. Pharmacokinetics and pharmacodynamics of irbesartan in healthy subjects. J Clin Pharmacol 1998 Mar; 38(3): 246–55PubMedGoogle Scholar
  13. 13.
    Pechère-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 Mar; 16(3): 385–93PubMedCrossRefGoogle Scholar
  14. 14.
    Sica DA, Marino MR, Hammett JL, et al. The pharmacokinetics of irbesartan in renal failure and maintenance hemodialysis. Clin Pharmacol Ther 1997 Dec; 62(6): 610–8PubMedCrossRefGoogle Scholar
  15. 15.
    Butzer R, Belz GG, Kober S, et al. Irbesartan results in more complete blockade of human adrenal AT1-receptor mediated effects than does candesartan cilexetil as evidenced by blunted plasma aldosterone levels [abstract no. P3.225]. J Hypertens 2000 Jun; 18 Suppl. 2: S209CrossRefGoogle Scholar
  16. 16.
    Kober S, Butzer R, Langguth P, et al. Extent and duration of angiotensin II antagonistic activity of irbesartan and candesartan cilexetil [abstract no. A105]. Am J Hypertension 2000 Apr; 13 (4 Pt 2): 150ACrossRefGoogle Scholar
  17. 17.
    Belz GG, Butzer R, Kober S, et al. Irbesartan results in more complete blockade of human renal AT1-receptor mediated effects than does candesartan cilexetil as evidenced by higher plasma renin levels [abstract no. A106]. Am J Hypertens 2000 Apr; 13 (4 Pt 2): 151ACrossRefGoogle Scholar
  18. 18.
    McIntyre M, MacFadyen RJ, Meredith PA, et al. Dose-ranging study of the angiotensin II receptor antagonist irbesartan (SR 47436/BMS-186295) on blood pressure and neurohormonal effects in salt-deplete men. J Cardiovasc Pharmacol 1996 Jul; 28(1): 101–6PubMedCrossRefGoogle Scholar
  19. 19.
    Azizi M, Bissery A, Bura-Riviere A, et al. Dual renin-angiotensin system blockade restores blood pressure-renin dependency in individuals with low renin concentrations. J Hypertens 2003 Oct; 21(10): 1887–95PubMedCrossRefGoogle Scholar
  20. 20.
    Lauten WB, Khan QA, Rajagopalan S, et al. Usefulness of quinapril and irbesartan to improve the anti-inflammatory response of atorvastatin and aspirin in patients with coronary artery disease. Am J Cardiol 2003 May 1; 91: 1116–9PubMedCrossRefGoogle Scholar
  21. 21.
    Burnier M, Pechere-Bertschi A, Nussberger J, et al. Studies of the renal effects of angiotensin II receptor blockade: the con-founding factor of acute water loading on the action of vasoac-tive systems. Am J Kidney Dis 1995 Jul; 26(1): 108–15PubMedCrossRefGoogle Scholar
  22. 22.
    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 Aug; 38(8): 702–7PubMedGoogle Scholar
  23. 23.
    Chando TJ, Everett DW, Kahle AD, et al. Biotransformation of irbesartan in man. Drug Metab Dispos 1998 May; 26(5): 408–17PubMedGoogle Scholar
  24. 24.
    Vachharajani NN, Shyu WC, Smith RA, et al. The effects of age and gender on the pharmacokinetics of irbesartan. Br J Clin Pharmacol 1998 Dec; 46(6): 611–3PubMedCrossRefGoogle Scholar
  25. 25.
    Marino MR, Langenbacher KM, Raymond RH, et al. Pharmacokinetics and pharmacodynamics of irbesartan in patients with hepatic cirrhosis. J Clin Pharmacol 1998 Apr; 38(4): 347–56PubMedGoogle Scholar
  26. 26.
    Kostis JB, Vachharajani NN, Hadjilambris OW, et al. The pharmacokinetics and pharmacodynamics of irbesartan in heart failure. J Clin Pharmacol 2001 Sep; 41(9): 935–42PubMedCrossRefGoogle Scholar
  27. 27.
    Vachharajani N, Shyu WC, Mantha S, et al. Lack of food effect on the oral bioavailability of irbesartan [abstract no. 60]. J Clin Pharmacology 1997 Sep; 37(9): 872Google Scholar
  28. 28.
    Morsing P, Adler G, Brandt-Eliasson U, et al. Mechanistic differences of various AT1-receptor blockers in isolated vessels of different origin. Hypertension 1999 Jun; 33(6): 1406–13PubMedCrossRefGoogle Scholar
  29. 29.
    Ruilope L. Human pharmacokinetic/pharmacodynamic profile of irbesartan: a new potent angiotensin II receptor antagonist. J Hypertens 1997 Dec; 15 Suppl. 7: S15–20Google Scholar
  30. 30.
    Perrier L, Bourrié M, Marti E, et al. In vitro N-glucuronidation of SR 474346 (BMS 186295), a new AT1 nonpeptide angiotensin II receptor antagonist, by rat, monkey and human hepatic microsomal fractions. J Pharmacol Exp Ther 1994 Oct; 271(1): 91–9PubMedGoogle Scholar
  31. 31.
    Bourrié M, Meunier V, Berger Y, et al. Role of cytochrome P-4502C9 in irbesartan oxidation by human liver microsomes. Drug Metab Dispos 1999 Feb; 27(2): 288–96PubMedGoogle Scholar
  32. 32.
    Marino MR, Vachharajani NN. Drug interactions with irbesartan. Clin Pharmacokinet 2001; 40(8): 605–14PubMedCrossRefGoogle Scholar
  33. 33.
    Marino MR, Hammett JL, Ferreira I, et al. Effect of nifedipine on the steady-state pharmacokinetics and pharmacodynamics of irbesartan in healthy subjects. J Cardiovasc Pharmacol Ther 1998 Apr; 3(2): 111–8PubMedCrossRefGoogle Scholar
  34. 34.
    Mangold B, Gielsdorf W, Marino MR. Irbesartan does not affect the steady-state pharmacodynamics and pharmacokinetics of warfarin. Eur J Clin Pharmacol 1999 Oct; 55(8): 593–8PubMedCrossRefGoogle Scholar
  35. 35.
    Marino MR, Vachharajani NN, Hadjilambris OW. Irbesartan does not affect the pharmacokinetics of simvastatin in healthy subjects. J Clin Pharmacol 2000 Aug; 40(8): 875–9PubMedCrossRefGoogle Scholar
  36. 36.
    Marino MR, Langenbacher KM, Mangold B, et al. Lack of drug interactions with irbesartan: a summary of five pharmacokinetic studies [abstract no. P31.096]. J Hypertens 1998 Jun; 16 Suppl. 2: S248Google Scholar
  37. 37.
    Kovacs SJ, Wilton JH, Blum RA. Steady state (SS) pharmacokinetics (PK) of irbesartan alone and in combination with fluconazole (F) [abstract no. PI-59]. Clin Pharmacol Ther 1999 Feb; 65(2): 132Google Scholar
  38. 38.
    Marino MR, Langenbacher KM, Ford NF, et al. Effect of hydrochlorothiazide on the pharmacokinetics and pharmacodynamics of the angiotensin II blocker irbesartan. Clin Drug Invest 1997 Nov; 14(5): 383–91CrossRefGoogle Scholar
  39. 39.
    Escolar M, Lopez de Ocariz A, Simon M, et al. Effects of antacids on irbesartan pharmacokinetics [abstract no. FC-9]. Meth Find Exp Clin Pharmacol 1998; 20 Suppl. A: 53CrossRefGoogle Scholar
  40. 40.
    Marino MR, Hammett JL, Ferreira I, et al. Effect of irbesartan on the steady-state pharmacokinetics of digoxin in healthy male subjects [abstract no. P-278E]. ASHP Midyear Clinical Meeting 1998; 33: 2301Google Scholar
  41. 41.
    Lacourcière Y. A multicenter, randomized, double-blind study of the antihypertensive efficacy and tolerability of irbesartan in patients aged ≥65 years with mild to moderate hypertension. Clin Ther 2000 Oct; 22(10): 1213–24PubMedCrossRefGoogle Scholar
  42. 42.
    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 Mar; 12(3): 203–8PubMedCrossRefGoogle Scholar
  43. 43.
    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. Clin Ther 2002 Jan; 24(1): 126–38PubMedCrossRefGoogle Scholar
  44. 44.
    Chiou K-R, Chen C-H, Ding PY-A, et al. Randomized, double-blind comparison of irbesartan and enalapril for treatment of mild to moderate hypertension. Chin Med J (Taipei) 2000 May; 63(5): 368–76Google Scholar
  45. 45.
    Neutel J, Germino W, Smith D, et al. The antihypertensive efficacy and safety of irbesartan compared with amlodipine for the treatment of mild-to-moderate hypertension [abstract no. D068]. Am J Hypertens 1999 Apr; 12 (4 Pt 2): 128A plus posterCrossRefGoogle Scholar
  46. 46.
    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 Apr; 7(2): 135–42PubMedCrossRefGoogle Scholar
  47. 47.
    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. Irbesartan/ Losartan Study Investigators [published erratum appears in Am J Hypertension 1998 Jun; 11 (6 Pt 1): 736]. Am J Hypertens 1998; 11 (4 Pt 1): 445–53PubMedCrossRefGoogle Scholar
  48. 48.
    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 Group Investigators. Clin Ther 1998 May–Jun; 20(3): 398–409PubMedCrossRefGoogle Scholar
  49. 49.
    Oparil S, Williams D, Chrysant SG, et al. Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension [published erratum appears in J Clin Hypertens (Greenwich) 2001 Nov–Dec; 3 (6): 395]. J Clin Hypertens (Greenwich) 2001 Sep–Oct; 3(5): 283–91, 318CrossRefGoogle Scholar
  50. 50.
    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 Jan; 7(1): 31–7PubMedCrossRefGoogle Scholar
  51. 51.
    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 Dec; 15 (12 Pt 1): 1511–8PubMedCrossRefGoogle Scholar
  52. 52.
    Pool JL, Guthrie RM, Littlejohn III TW, et al. Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension. Am J Hypertens 1998 Apr; 11 (4 Pt 1): 462–70PubMedCrossRefGoogle Scholar
  53. 53.
    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. Multicentre Investigators. Clin Drug Invest 1998 Mar; 15(3): 217–27CrossRefGoogle Scholar
  54. 54.
    Reeves RA, Lin C-S, Kassler-Taub K, et al. Dose-related efficacy of irbesartan for hypertension: an integrated analysis. Hypertension 1998 Jun; 31(6): 1311–6PubMedCrossRefGoogle Scholar
  55. 55.
    Weber M, Saini R, Kassler-Taub K, et al. Irbesartan combined with low-dose hydrochlorothiazide for mild-to-moderate hypertension [abstract no. P16.27]. J Hypertens 1998 Jun; 16 Suppl. 2: S129Google Scholar
  56. 56.
    Howe P, Phillips P, Saini R, et al. The antihypertensive efficacy of the combination of irbesartan and hydrochlorothiazide assessed by 24-hour ambulatory blood pressure monitoring. Clin Exper Hypertension 1999 Nov; 21(8): 1373–96CrossRefGoogle Scholar
  57. 57.
    Rosenstock J, Rossi L, Lin CS, et al. The effects of irbesartan added to hydrochlorothiazide for the treatment of hypertension in patients non-responsive to hydrochlorothiazide alone. J Clin Pharm Ther 1998 Dec; 23(6): 433–40PubMedCrossRefGoogle Scholar
  58. 58.
    Weir MR, Tolchin N, Toth P, et al. Addition of hydrochlorothiazide to irbesartan produces further dose-related reductions in blood pressure within two weeks [abstract no. P16.34]. J Hypertens 1998 Jun; 16 Suppl. 2: S130Google Scholar
  59. 59.
    Kochar M, Guthrie R, Triscari J, et al. Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension. Am J Hypertens 1999; 12 (8 Pt 1): 797–805PubMedCrossRefGoogle Scholar
  60. 60.
    Larochelle P, Flack JM, Marbury TC, et al. Effects and tolerability of irbesartan versus enalapril in patients with severe hypertension: Irbesartan Multicenter Investigators. Am J Cardiol 1997 Dec 15; 80(12): 1613–5PubMedCrossRefGoogle Scholar
  61. 61.
    Littlejohn III T, Saini R, Kassler-Taub K, et al. Long-term safety and antihypertensive efficacy of irbesartan: pooled results of five open-label studies. Clin Exper Hypertension 1999 Nov; 21(8): 1273–95CrossRefGoogle Scholar
  62. 62.
    Raskin P, Guthrie R, Flack JM, et al. The long-term antihypertensive activity and tolerability of irbesartan with hydrochlorothiazide. J Hum Hypertens 1999 Oct; 13(10): 683–7PubMedCrossRefGoogle Scholar
  63. 63.
    Bays HE, Park JS, Reilly K, et al. Irbesartan safety and effectiveness; a postmarketing surveillance study [abstract no. D039]. AST investigators. Am J Hypertens 1999; 12 (4 Pt 2): 120ACrossRefGoogle Scholar
  64. 64.
    Kurland L, Melhus H, Karlsson J, et al. Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients. J Hypertens 2001 Oct; 19: 1783–7PubMedCrossRefGoogle Scholar
  65. 65.
    Kurland L, Melhus H, Karlsson J, et al. Aldosterone synthase (CYP11B2)-344 C/T polymorphism is related to antihyperten-sive response: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation Versus Atenolol (SILVHIA) trial. Am J Hypertens 2002; 15(5): 389–93PubMedCrossRefGoogle Scholar
  66. 66.
    Cushman WC, Ford CE, Cutler JA, et al. Success and predictors of blood pressure control in diverse North American settings: the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT). J Clin Hypertens 2002 Nov–Dec; 4(6): 393–404CrossRefGoogle Scholar
  67. 67.
    Coca A, Calvo C, Sobrino J, et al. Once-daily fixed-combination irbesartan 300mg/hydrochlorothiazide 25mg and circadian blood pressure profile in patients with essential hypertension. Clin Ther 2003 Nov; 25(11): 2849–64PubMedCrossRefGoogle Scholar
  68. 68.
    Kannel WB, Levy D, Cupples LA. Left ventricular hypertrophy and risk of cardiac failure: insights from the Framingham Study. J Cardiovasc Pharmacol 1987; 10 Suppl. 6: S135–40PubMedGoogle Scholar
  69. 69.
    Levy D, Garrison RJ, Savage DD, et al. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990 May 31; 322(22): 1561–6PubMedCrossRefGoogle Scholar
  70. 70.
    McLenachan JM, Henderson E, Morris KI, et al. Ventricular arrhythmias in patients with hypertensive left ventricular hypertrophy. N Engl J Med 1987 Sep 24; 317(13): 787–92PubMedCrossRefGoogle Scholar
  71. 71.
    Villatico Campbell S, Rizzo V, Di Maio F, et al. Comparison of irbesartan versus enalapril on left ventricular mass and function in stage I–II hypertensives [abstract no. P.70]. J Hypertens 1998 Jun; 16 Suppl. 2: S18Google Scholar
  72. 72.
    Feraco E. Therapeutic effects of irbesartan in left ventricular hypertrophy [abstract no. DO19]. Am J Hypertens 1999 Apr; 12 (4 Pt 2): 115AGoogle Scholar
  73. 73.
    Malmqvist K, Kahan T, Edner M, et al. Regression of left ventricular hypertrophy in human hypertension with irbesartan. J Hypertens 2001 Jun; 19(6): 1167–76PubMedCrossRefGoogle Scholar
  74. 74.
    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 Nov; 42(5): 622–8PubMedCrossRefGoogle Scholar
  75. 75.
    Malmqvist K, Kahan T, Edner M, et al. 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 Nov 15; 90(10): 1107–12PubMedCrossRefGoogle Scholar
  76. 76.
    Pohl M, Cooper M, Ulrey J, et al. Safety and efficacy of irbesartan in hypertensive patients with type II diabetes and proteinuria [abstract no. D4]. Am J Hypertens 1997 Apr; 10 (Pt 2): 105CrossRefGoogle Scholar
  77. 77.
    Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001 Sep 20; 345(12): 870–8PubMedCrossRefGoogle Scholar
  78. 78.
    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 Sep 20; 345(12): 851–60PubMedCrossRefGoogle Scholar
  79. 79.
    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 Nov; 25(11): 1909–13PubMedCrossRefGoogle Scholar
  80. 80.
    Rossing K, Christensen PK, Andersen S, et al. Comparative effects of irbesartan on ambulatory and office blood pressure: a substudy of ambulatory blood pressure from the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study. Diabetes Care 2003 Mar; 26(3): 569–74PubMedCrossRefGoogle Scholar
  81. 81.
    Andersen S, Bröchner-Mortensen J, Parving H-H. Kidney function during and after withdrawal of long-term irbesartan treatment in patients with type 2 diabetes and microalbuminuria: Irbesartan in patients with type 2 diabetes and microalbuminuria Study Group. Diabetes Care 2003 Dec; 26(12): 3296–302PubMedCrossRefGoogle Scholar
  82. 82.
    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: Collaborative Study Group. Ann Intern Med 2003 Apr 1; 138(7): 542–9PubMedGoogle Scholar
  83. 83.
    Palmer AJ, Annemans L, Roze S, et al. 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 Oct; 18(10): 2059–66PubMedCrossRefGoogle Scholar
  84. 84.
    Rodby RA, Chiou C-F, Borenstein J, et al. The cost-effectiveness of irbesartan in the treatment of hypertensive patients with type 2 diabetic nephropathy. Clin Ther 2003; 25(7): 2102–19PubMedCrossRefGoogle Scholar
  85. 85.
    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 Jan; 20(1): 71–9PubMedGoogle Scholar
  86. 86.
    Koch H, Pirk O, Schöffski, et al. Treatment of hypertensive type 2 diabetics (t2d) with irbesartan (Irb) is cost-saving due to prevented or delayed end-stage renal disease [abstract no. 22]. Int J Clin Pharm and Ther 2003; 41(11): 537–8Google Scholar
  87. 87.
    Simon TA, Gelarden RT, Freitag SA, et al. Safety of irbesartan in the treatment of mild to moderate systemic hypertension. Am J Cardiol 1998 Jul; 82(2): 179–82PubMedCrossRefGoogle Scholar
  88. 88.
    Sanofi Pharma, Bristol-Myers Squibb SNC. Aprovel 75mg tablets; Aprovel 150mg tablets; Aprovel 300mg tablets: summary of product characteristics. Paris: Sanofi Pharma, Bristol-Myers Squibb SNC, 2002 JunGoogle Scholar
  89. 89.
    Bristol-Myers Squibb Company, Sanofi-Synthelabo. Avalide® (irbesartan-hydrochlorothiazide) tablets: prescribing information. New York: Bristol-Myers Squibb Sanofi-Synthelabo Partnership, 2002 AprGoogle Scholar
  90. 90.
    Bristol-Myers Squibb Company, Sanofi-Synthelabo. Avapro® (irbesartan) tablets: prescribing information. New York: Bristol-Myers Squibb Sanofi-Synthelabo Partnership, 2002 AugGoogle Scholar
  91. 91.
    Sweetman SC. Martindale: the complete drug reference. 33rd ed. London: Pharmaceutical Press, 2002Google Scholar
  92. 92.
    Sanofi-Synthelabo Australia Pty Limited. Product information: Karvea® (irbesartan) [online]. Available from URL: http://www.sanofi-synthelabo.co.au [Accessed 2004 Mar 23]
  93. 93.
    Doctor’s Guide. Health Canada approves Avapro (irbesartan) for the treatment of diabetic renal disease [online]. Available from URL: http://www.pslgroup.com/dg [Accessed 2004 Mar 23]
  94. 94.
    World Health Organization. The world health report 2002: risks to health 2002. Quantifying Selected Major Risks to health. Geneva: World Health Organization, 2002: 47–96Google Scholar
  95. 95.
    Collins R, MacMahon S. Blood pressure, antihypertensive drug treatment and the risks of stroke and of coronary heart disease. Br Med Bull 1994 Apr; 50(2): 272–98PubMedGoogle Scholar
  96. 96.
    World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO)/ International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens 2003 Nov; 21(11): 1983–92CrossRefGoogle Scholar
  97. 97.
    Guidelines Committee. 2003 European Society of Hypertension —European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003 Jun; 21(6): 1011–53CrossRefGoogle Scholar
  98. 98.
    Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [published erratum appears in JAMA 2003 Jul 9; 290(2): 197]. JAMA 2003 May 21; 289(19): 2560–72PubMedCrossRefGoogle Scholar
  99. 99.
    Parati G, Pomidossi G, Albini F, et al. Relationship of 24-hour blood pressure mean and variability to severity of target-organ damage in hypertension. J Hypertens 1987 Feb; 5(1): 93–8PubMedCrossRefGoogle Scholar
  100. 100.
    Frattola A, Parati G, Cuspidi C, et al. Prognostic value of 24-hour blood pressure variability. J Hypertens 1993 Oct; 11(10): 1133–7PubMedCrossRefGoogle Scholar
  101. 101.
    Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002 Mar 23; 359(9311): 995–1003PubMedCrossRefGoogle Scholar
  102. 102.
    Lindholm LH, Ibsen H, Dahlöf B, et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002 Mar 23; 359(9311): 1004–10PubMedCrossRefGoogle Scholar
  103. 103.
    Amos AF, McCarty DJ, Zimmet P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabetic Med 1997; 14 Suppl. 5: 1–85Google Scholar
  104. 104.
    Ritz E, Rychlik I, Locatelli F, et al. End-stage renal failure in type 2 diabetes: A medical catastrophe of worldwide dimensions. Am J Kidney Dis 1999 Nov; 34(5): 795–808PubMedCrossRefGoogle Scholar
  105. 105.
    United States Renal Data System. 2001 Annual Data Report: atlas of end-stage renal disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease, Bethesda, MD, 2001. Chapter 1: 37–52Google Scholar
  106. 106.
    Parving HH, Andersen AR, Smidt UM, et al. Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet 1983 May 28; 1(8335): 1175–9PubMedCrossRefGoogle Scholar
  107. 107.
    Mogensen CE. Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy. Br Med J (Clin Res Ed) 1982 Sep 11; 285(6343): 685–8CrossRefGoogle Scholar
  108. 108.
    UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group [published erratum appears in Br Med J 1999 Jan 2; 318 (7175): 29]. Br Med J 1998 Sep 12; 317(7160): 703–13CrossRefGoogle Scholar
  109. 109.
    Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation (HOPE) Study Investigators [published erratum appears in Lancet 2000 Sep 2; 356 (9232): 860]. Lancet 2000 Jan 22; 355(9200): 253–9CrossRefGoogle Scholar
  110. 110.
    Estacio RO, Jeffers BW, Gifford N, et al. Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes mellitus. Diabetes Care 2000 Apr; 23 Suppl. 2: B54–64PubMedGoogle Scholar
  111. 111.
    Salvetti A, Mattei P, Sudano I. Renal protection and antihypertensive drugs: current status. Drugs 1999 May; 57(5): 665–93PubMedCrossRefGoogle Scholar
  112. 112.
    Parving HH, Tarnow L, Rossing P. Renal protection in diabetes: an emerging role for calcium antagonists. J Hypertens 1996 Nov; 14 Suppl. 4: S21–5CrossRefGoogle Scholar
  113. 113.
    Toto R. Angiotensin II subtype 1 receptor blockers and renal function. Arch Intern Med 2001 Jun 25; 161(12): 1492–9PubMedCrossRefGoogle Scholar
  114. 114.
    Ramsay LE, Williams B, Johnston GD, et al. British Hypertension Society guidelines for hypertension management 1999: summary. BMJ 1999 Sep 4; 319(7210): 630–5PubMedCrossRefGoogle Scholar
  115. 115.
    Bakris GL, Williams M, Dworkin L, 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 Disease 2000 Sep; 36(3): 646–61Google Scholar
  116. 116.
    Meltzer S, Leiter L, Daneman D, et al. 1998 clinical practice guidelines for the management of diabetes in Canada: Canadian Diabetes Association. CMAJ 1998; 159 Suppl. 8: 1–29Google Scholar
  117. 117.
    Arauz-Pacheco C, Parrott MA, Raskin P, et al. Treatment of hypertension in adults with diabetes. American Diabetes Association. Diabetes Care 2003 Jan; 26 Suppl. 1: S80–2PubMedCrossRefGoogle Scholar
  118. 118.
    Joint British recommendations on prevention of coronary heart disease in clinical practice: summary. British Cardiac Society, British Hyperlipidaemia Association, British Hypertension Society, British Diabetic Association. BMJ 2000 Mar 11; 320(7236): 705–8CrossRefGoogle Scholar
  119. 119.
    Cooper ME. Pathogenesis, prevention, and treatment of diabetic nephropathy. Lancet 1998 Jul 18; 352(9123): 213–9PubMedCrossRefGoogle Scholar
  120. 120.
    Ruilope L. RAS blockade: new possibilities in the treatment of complications of diabetes. Heart 2000 Sep; 84 Suppl. 1: i32–4, discussion i50PubMedCrossRefGoogle Scholar
  121. 121.
    Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy: the Collaborative Study Group [published erratum appears in N Engl J Med 1993 Jan 13; 330 (2): 152]. N Engl J Med 1993 Nov 11; 329(20): 1456–62PubMedCrossRefGoogle Scholar
  122. 122.
    Viberti G, Mogensen CE, Groop LC, et al. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria: European Microalbuminuria Captopril Study Group. JAMA 1994 Jan 26; 271(4): 275–9PubMedCrossRefGoogle Scholar
  123. 123.
    Mogensen CE, Neldam S, Tikkanen I, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the Candesartan And Lisinopril Microalbuminuria (CALM) study. BMJ 2000 Dec 9; 321(7274): 1440–4PubMedCrossRefGoogle Scholar
  124. 124.
    Agardh CD, Garcia-Puig J, Charbonnel B, et al. Greater reduction of urinary albumin excretion in hypertensive type II diabetic patients with incipient nephropathy by lisinopril than by nifedipine. J Hum Hypertens 1996 Mar; 10(3): 185–92PubMedGoogle Scholar
  125. 125.
    Lacourcière Y, Belanger A, Godin C, et al. Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy. Kidney Int 2000 Aug; 58(2): 762–9PubMedCrossRefGoogle Scholar
  126. 126.
    Schnack C, Hoffmann W, Hopmeier P, et al. Renal and metabolic effects of 1-year treatment with ramipril or atenolol in NIDDM patients with microalbuminuria. Diabetologia 1996 Dec; 39(12): 1611–6PubMedCrossRefGoogle Scholar
  127. 127.
    Nielsen FS, Rossing P, Gall MA, et al. Long-term effect of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy. Diabetes 1997 Jul; 46(7): 1182–8PubMedCrossRefGoogle Scholar
  128. 128.
    Bakris GL, Copley JB, Vicknair N, et al. Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Kidney Int 1996 Nov; 50(5): 1641–50PubMedCrossRefGoogle Scholar
  129. 129.
    Ravid M, Lang R, Rachmani R, et al. Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus: a 7-year follow-up study. Arch Intern Med 1996 Feb 12; 156(3): 286–9PubMedCrossRefGoogle Scholar
  130. 130.
    Gansevoort RT, Sluiter WJ, Hemmelder MH, et al. Antiproteinuric effect of blood-pressure-lowering agents: a meta-analysis of comparative trials. Nephrol Dial Transplant 1995 Nov; 10(11): 1963–74PubMedGoogle Scholar
  131. 131.
    Kasiske BL, Kalil RS, Ma JZ, et al. Effect of antihypertensive therapy on the kidney in patients with diabetes: a meta-regression analysis. Ann Intern Med 1993 Jan 15; 118(2): 129–38PubMedGoogle Scholar
  132. 132.
    Weidmann P, Schneider M, Bohlen L. Therapeutic efficacy of different antihypertensive drugs in human diabetic nephropathy: an updated meta-analysis. Nephrol Dial Transplant 1995 Oct; 10 Suppl 9: 39–45Google Scholar
  133. 133.
    Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001 Sep 20; 345(12): 861–9PubMedCrossRefGoogle Scholar
  134. 134.
    Muirhead N, Feagan BF, Mahon J, et al. The effects of valsartan and captopril on reducing microalbuminuria in patients with type 2 diabetes mellitus: a placebo-controlled trial. Curr Ther Res 1999 Dec; 60: 650–60CrossRefGoogle Scholar
  135. 135.
    Viberti G, Wheeldon NM, 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: 672–8PubMedCrossRefGoogle Scholar
  136. 136.
    Molitch ME, De Fronzo RA, Franz MJ, et al. Diabetic nephropathy: American Diabetes Association. Diabetes Care 2003 Jan; 26 Suppl. 1: S94–8PubMedCrossRefGoogle Scholar
  137. 137.
    Working Party of the International Diabetes Federation (European Region). Hypertension in people with type 2 diabetes: knowledge-based diabetes-specific guidelines. Diabet Med 2003 Dec; 20(12): 972–87CrossRefGoogle Scholar
  138. 138.
    Pylypchuk GB. ACE inhibitor-versus angiotensin II blocker-induced cough and angioedema. Ann Pharmacother 1998 Oct; 32(10): 1060–6PubMedCrossRefGoogle Scholar
  139. 139.
    Mazzolai L, Burnier M. Comparative safety and tolerability of angiotensin II receptor antagonists. Drug Saf 1999 Jul; 21(1): 23–33PubMedCrossRefGoogle Scholar
  140. 140.
    Lacourcière Y, Brunner H, Irwin R, et al. Effects of modulators of the renin-angiotensin-aldosterone system on cough: Losartan Cough Study Group. J Hypertens 1994 Dec; 12(12): 1387–93PubMedGoogle Scholar
  141. 141.
    Benz J, Oshrain C, Henry D, et al. Valsartan, a new angiotensin II receptor antagonist: a double-blind study comparing the incidence of cough with lisinopril and hydrochlorothiazide. J Clin Pharmacol 1997 Feb; 37(2): 101–7PubMedGoogle Scholar
  142. 142.
    Rossing K, Christensen PK, Jensen BR, et al. Dual blockade of the renin-angiotensin system in diabetic nephropathy: a randomized double-blind crossover study. Diabetes Care 2002 Jan; 25(1): 95–100PubMedCrossRefGoogle Scholar
  143. 143.
    Jacobsen P, Andersen S, Rossing K, et al. Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy. Nephrol Dial Transplant 2002 Jun; 17(6): 1019–24PubMedCrossRefGoogle Scholar
  144. 144.
    Jacobsen P, Andersen S, Rossing K, et al. Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy. Kidney Int 2003 May; 63(5): 1874–80PubMedCrossRefGoogle Scholar
  145. 145.
    Jacobsen P, Andersen S, Jensen BR, et al. Additive effect of ACE inhibition and angiotensin II receptor blockade in type I diabetic patients with diabetic nephropathy. J Am Soc Nephrol 2003; 14: 992–9PubMedCrossRefGoogle Scholar
  146. 146.
    Rossing K, Jacobsen P, Pietraszek L, et al. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy. Diabetes Care 2003; 26(8): 2268–74PubMedCrossRefGoogle Scholar
  147. 147.
    Cannon CP. Innovative directions in th future role of antiplatelet agents. In: Califf RM, Topol EJ, Mehta SR et al. Therapeutic Challenges in the Treatment of Cardiovascular Disease: issue and answers [online]. Available from URL: http://www.medscape.com/viewprogram/2891_pnt [Accessed 2004 Mar 9]
  148. 148.
    Bannerjee P, Clark AL, Cleland JGF. Diastolic heart failure: a difficult problem in the elderly. Am J Geriatr Cardiol 2004; 13(1): 16–21CrossRefGoogle Scholar

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© Adis Data Information BV 2004

Authors and Affiliations

  • Katherine F. Croom
    • 1
  • Monique P. Curran
    • 1
  • Karen L. Goa
    • 1
  • Caroline M. Perry
    • 1
  1. 1.Adis International LimitedMairangi Bay, AucklandNew Zealand

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