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Journal of Renin-Angiotensin-Aldosterone System
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Combination is better than monotherapy with ACE inhibitor or angiotensin receptor antagonist at recommended doses

Julián Segura

Hypertension Unit, Nephrology Department, Hospital 12 de Octubre, Madrid, Spain, jsegurad{at}senefro.org

Manuel Praga

Hypertension Unit, Nephrology Department, Hospital 12 de Octubre, Madrid, Spain

Carlos Campo

Hypertension Unit, Nephrology Department, Hospital 12 de Octubre, Madrid, Spain

José L Rodicio

Hypertension Unit, Nephrology Department, Hospital 12 de Octubre, Madrid, Spain

Luis M Ruilope

Hypertension Unit, Nephrology Department, Hospital 12 de Octubre, Madrid, Spain

Objective

The combination of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor antagonist (ARB) could provide a higher degree of blockade of the renin-angiotensin system(RAS) than either agent alone. The primary aim of this study was to look at the effect of three therapeutic regimens (titrated ACE inhibitor (ACE-I) versus titrated ARB versus the combination of an ACE-I and an ARB) on the attainment of adequate blood pressure (BP) control and antiproteinuric effect. Both ACE-I and ARB were titrated as monotherapy up to the maximal recommended dose.

Methods

A pilot randomised, parallel group open-label study was conducted in 36 patients with primary renal disease, proteinuria above 1.5 g/day and BP >140/90 mmHg while on therapy with an ACE-I. Patients were randomly assigned to (1) benazepril, n=12; (2) valsartan, n=12; or (3) benazepril plus valsartan, n=12. Other antihypertensive therapies could also be added to attain goal BP (<140/90 mmHg). The primary endpoint was the change in proteinuria during six months of follow-up.

Results

In the presence of similar BP decreasesand stable creatinine clearance values, mean proteinuria decreases were 0.5±1.7, 1.2±2.0 and 2.5±1.8 g/day in groups 1, 2 and 3, respectively. When compared with baseline values, only the fall induced by the combination of ARB and ACE-I attained statistical significance (p<0.05).

Conclusion

The antiproteinuric capacity of monotherapy at recommended doses with either an ACE-I or an ARB is lower than that obtained with the combination of the two drugs.

Key Words: angiotensin-converting enzyme inhibitor • angiotensin receptor blocker • renin-angiotensin system inhibition • mild renal insufficiency • proteinuria

References

  • Taguma Y., Kitamoto Y., Futaki G. et al. Effect of captopril on heavy proteinuria in azotemic diabetics. N Engl J Med 1985;313:1617-20.[Abstract]
  • Lewis EJ, Hunsicker LG, Bain RP, Rohde RD The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy: The Collaborative Study Group. N Engl J Med 1993;329:1456-62.[Abstract/Free Full Text]
  • Ruilope LM, Miranda B., OlietA. et al. Control of hypertension with the angiotensin converting enzyme inhibitor captopril reduces glomerular proteinuria. J Hypertens 1988;4:S467-S69.
  • The Gisen Group. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997;349:1857-63.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Maschio G., Alberti D., Janin G. et al. Effect of the angiotensin-converting enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med 1996; 334:939-45.[Abstract/Free Full Text]
  • Ihle BU,Whitworth JA, Shahinfar S., Cnaan A., Kincaid-Smith PS, Becker GJ Angiotensin-converting enzyme inhibition in nondiabetic progressive renal insufficiency: a controlled double-blind trial. Am J Kidney Dis 1996;27:489-95.[Web of Science][Medline] [Order article via Infotrieve]
  • Giatras I., Lau J., Levey AS for the Angiotensin-Converting Enzyme Inhibition and Progressive Renal Disease Study Group: Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease: A meta-analysis of randomised trials. Ann Intern Med 1997;127:337-47.[Abstract/Free Full Text]
  • Carretero OA, Scicli AG The kallikrein-kinin system as a regulator of cardiovascular and renal function. In: Brenner BM, Laragh JH (eds.). Hypertension: Pathophysiology, Diagnosis, and Management, 2nd edn. New York: Raven Press, 1995;98399.
  • Juillerat L., Nussberger J., Menard J. et al. Determinants of Iangiotensin II generation during converting enzyme inhibition. Hypertension 1990;16:564-72.[Abstract/Free Full Text]
  • Urata H., Nishimura H., Ganten D. Chymase-dependent angiotensin II forming system in humans. Am J Hypertens 1996;9:277-84.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Swedberg K., Eneroth P., Kjekshus J., Wilhelmson L. Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. Circulation 1990;82:1730-6.[Abstract/Free Full Text]
  • Mooser V., Nussberger J., Juillerat L. et al. Reactive hyperreninemia is a major determinant of plasma angiotensin II during ACE inhibition. J Cardiovasc Pharmacol 1990;15:276-82.[Web of Science][Medline] [Order article via Infotrieve]
  • Timmermans PB, Wong PC, Chiu AT et al. Angiotensin II receptor and angiotensin II receptor antagonists. Pharmacol Rev 1993;45:205-51.[Web of Science][Medline] [Order article via Infotrieve]
  • Goodfriend TL, Elliot ME, Catt KJ Angiotensin receptors and their antagonists. N Engl J Med 1996;334:1649-54.[Free Full Text]
  • Gansevoort R., de Zeeuw D., Shahinfar S., RedfieldA, de Jong PE Effects of the angiotensin II antagonist losartan in hypertensive patients with renal disease. J Hypertens 1994;12(suppl 2):S37-S42.
  • Gansevoort RT, de Zeeuw D., de Jong PE Is the antiproteinuric effect of ACE inhibition mediated by interference in the renin-angiotensin system? Kidney Int 1994;45:861-7.[Web of Science][Medline] [Order article via Infotrieve]
  • Nielsen S., Dollerup J., Nielsen B., Jensen Hae, Mogensen CE Losartan reduces albuminuria in patients with essential hypertension. An enalapril controlled 3 months study. Nephrol Dial Transplant 1997;12(suppl 2):19-23.[Free Full Text]
  • Chan JCN, Critchley Jajh, Tomlinson B., Chan TYK, Cockram CS Antihypertensive and anti-albuminuric effects of losartan potassium and felodipine in Chinese elderly hypertensive patients with or without non-insulin-dependent diabetes mellitus. Am J Nephrol 1997;17:72-80.[Web of Science][Medline] [Order article via Infotrieve]
  • Parving HH, Lehnert H., Brochner-Mortensen J., Gomis R., Andersen S., Arner P. Effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001;345:870-8.[Abstract/Free Full Text]
  • 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 Eng J Med 2001;345:851-60.[Abstract/Free Full Text]
  • 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;345:861-9.[Abstract/Free Full Text]
  • Ruilope LM,Aldigier J., Ponticelli C., Oddou-Stock P., Botteri F., Mann JF Safety of the combination of valsartan and benazepril in patients with chronic renal disease. J Hypertens 2000;18:89-95.[Web of Science][Medline] [Order article via Infotrieve]
  • Stergiou GS, Skeva II, Baibas NM et al.Additive hypotensive effect of angiotensin-converting enzyme inhibition and angiotensin-receptor antagonism in essential hypertension. J Cardiovasc Pharmacol 2000;36:937-41.
  • Azizi M., Linhart A., Alexander J. et al. Pilot study of combined blockade of the renin-angiotensin system in essential hypertensive patients. J Hypertens 2000;8:1139-47.
  • Azizi M., Guyene TT, Chatelier G., Menard J. Pharmacological demonstration of the additive effects of angiotensin-converting enzyme inhibition and angiotensin II antagonism in sodium depleted healthy subjects. Clin Exp Hypertens 1997;19:937-51.[Web of Science][Medline] [Order article via Infotrieve]
  • Mogensen CE, Neldam S., Tikkanen I. et al. for the CALM study group. 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;321:1440-4.[Abstract/Free Full Text]
  • Russo D., Pisani A., Balleta MM et al. Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy. Am J Kidney Dis 1999;33:851-6.[Web of Science][Medline] [Order article via Infotrieve]
  • Kincaid-Smith P., Fairley K., Packhman D. Randomised controlled crossover study of the effect on proteinuria and blood pressure of adding an angiotensin II receptor antagonist to an angiotensin converting enzyme inhibitor in normotensive patients with chronic renal disease and proteinuria. Nephrol Dial Transplant 2002;17:597-601.[Abstract/Free Full Text]
  • Peterson JC, Adler S., Bukart JM et al., for the Modification of Diet in Renal Disease (MDRD) Study Group. Blood pressure control, proteinuria and the progression of renal disease. Ann Intern Med 1995;123:754-62.[Abstract/Free Full Text]
  • Remuzzi G., Ruggenenti P., Benigni A. Understanding the nature of renal disease progression. Kidney Int 1997;51:2-11.[Web of Science][Medline] [Order article via Infotrieve]
  • Kaiser G., Ackermann R., Sioufi A. Pharmacokinetics of a new angiotensin-converting enzyme inhibitor, benazepril hydrochloride, in special population. Am Heart J 1989; 117:746-51.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Keilani T., Danesh FR, Schlueter WA, Molteni A., Battle D. A subdepressor dose of ramipril lowers urinary protein excretion without increasing plasma potassium. Am J Kidney Dis 1999;33:450-7.[Web of Science][Medline] [Order article via Infotrieve]
  • Flack JM,Yunis C., Preisser et al.The rapidity of drug dose escalation influences blood pressure response and adverse effects burden in patients with hypertension: the Quinapril Titration Interval Management Evaluation (ATIME) Study. ATIME Research Group. Arch Intern Med 2000;160:1842-7.[Abstract/Free Full Text]
  • Carter BL Dosing of antihypertensive medications in patients with renal insufficiency. J Clin Pharmacol 1995; 35:81-6.[Abstract]
  • Pollack D., Divish B., Polakowski J., OpgenorthT.Angiotensin II receptor blockade improves renal function in rats with reduced renal mass. J Pharmacol Exp Ther 1993;267:657-63.[Abstract/Free Full Text]
  • Okada H., Suzuki H., Kanno H., Saruta T. Renal responses to angiotensin receptor antagonists and angiotensin-converting enzyme inhibitor in partially nephrectomized spontaneously hypertensive rats. J Cardiovasc Pharmacol 1995;26:564-70.[Web of Science][Medline] [Order article via Infotrieve]
  • RemuzziA, Perico N.,Amuchastegui C. et al. Short and long term effect of angiotensin II receptor blockade in rats with experimental diabetes. J Am Soc Nephrol 1993;4:40-9.[Abstract]
  • Obata J., Nakamura T., Kuroyanagi R., Yoshida Y., Guo DF, Inagami T. Candesartan prevents the progression of glomerulosclerosis in genetically hypertensive rats. Kidney Int 1997;63(suppl):S229-S231.
  • Benediktsson H., Chea R., Davidoff A., Paul LC Antihypertensive drug treatment in chronic renal allograft rejection in the rat. Transplantation 1996;62:1634-42.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Amuchastegui CS, Azzollini N., Mister M., Pezzotta A., Perico N., Remuzzi G. Chronic allograft nephropathy in the rat is improved by angiotensin II receptor blockade but not by calcium channel antagonism. J Am Soc Nephrol 1998;9:194855.
  • Leidig MF, Delles C.,Weidinger G., Schmieder RE A pharmacokinetic study of valsartan in hypertensive patients with normal renal function and on chronic hemodialysis. J Am Soc Nephrol 2000;11:350A (abstract).[CrossRef]
  • Jardine G., Mann JF, Oddou P., Mann J., Pedersen T., Ruilope LM Valsartan is effective in patients with post-transplant hypertension. J Am Soc Nephrol 2000;11:692A (abstract).
  • Wilkinson-Berka JL, Gibbs NJ, Cooper ME, Skinner SL, Kelly DJ Renoprotective and antihypertensive effects of combined valsartan and perindopril in progressive diabetic nephropathy in the transgenic (mRen-2)27 rat. Nephrol Dial Transplant 2001;16:1343-9.[Abstract/Free Full Text]
  • Plum J., Bünten B., Nemeth R., Grabensee B. Effects of angiotensin II antagonist valsartan on blood pressure, proteinuria, and renal hemodynamics in patients with chronic renal failure. J Am Soc Nephrol 1998;9:2223-34.[Abstract]
  • Forclaz A., Maillard M., Nussberger J., Brunner HR, Burnier M. Angiotensin II receptor blockade: Is there truly a benefit of adding an ACE inhibitor? Hypertension 2003;41:31-6.[Abstract/Free Full Text]
  • Menard J., Campbell DJ, Azizi M., Gonzales MF Synergistic effects of ACE inhibition and AII antagonism on blood pressure, cardiac weight, and renin in spontaneously hypertensive rat. Circulation 1997;96:3072-8.[Abstract/Free Full Text]
  • Hamroff G., Katz SD, Mancini D. et al. Addition of angiotensin II receptor blockade to maximal angiotensin-converting enzyme inhibition improves exercise capacity in patients with severe congestive heart failure. Circulation 1999;99:990-2.[Abstract/Free Full Text]
  • Tonkon M.,Awan N., Niazi I. et al.A study of the efficacy and safety of irbesartan in combination with conventional therapy, including ACE inhibitors, in heart failure. Irbesartan Heart Failure Group. Int J Clin Pract 2000;54:11-18.[Web of Science][Medline] [Order article via Infotrieve]

Journal of Renin-Angiotensin-Aldosterone System, Vol. 4, No. 1, 43-47 (2003)
DOI: 10.3317/jraas.2003.007


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