HOME HELP SUBSCRIBE ARCHIVE SEARCH TABLE OF CONTENTS FEEDBACK EDITORIAL BOARD ABOUT DOC NEWS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Services Email this article to a friend Similar articles in this journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                What's this?

ACE inhibitor–ARB Combination therapy May Be indicated forNephropathy

Question: Should I use an angiotensin-converting enzyme (ACE)inhibitor and an angiotensin II receptor blocker (ARB) together in primarycare for diabetic patients on their way toward renal disease and/or otherchronic complications?

Answer: Theoretically, the idea of dual blockade of thereninangiotensin-aldosterone system (RAAS) with agents of both classes isattractive, as neither ACE inhibition nor angiotensin II receptor blockadealone leads to complete blockade of RAAS, and clinical trials of each classalone have demonstrated slowing but not arrest of nephropathy progression.

Only a few human clinical studies have provided evidence that combinationtherapy may be of more benefit than monotherapy in slowing progression ofdiabetic nephropathy with respect to albuminurialevels.^1–3In the largest, the Candesartan and Lisinopril Microalbuminuria (CALM) studyof 199 diabetic subjects, candesartan plus lisinopril therapy for 6 months ledto greater blood pressure reduction than either agent alone, as well asgreater reduction inmicroalbuminuria.¹The Valsartan Heart Failure Trial (Val-heFT) demonstrated the cardiovascularbenefit of adding valsartan for patients with diabetes and heart failurealready on an ACEinhibitor.⁴ TheCHARM-Added trial showed cardiovascular benefit with the addition ofcandesartan to baseline ACE-inhibitor therapy in heart failurepatients.⁵

However, in these studies it is not clear whether the benefits are due tothe greater blood pressure lowering usually seen or to more complete RAASblockade. Furthermore, in none of these studies was the addition of the ARBcompared with the addition of another second non–RAAS-inhibiting drugwith identical blood pressure–lowering benefits with respect toprogression of nephropathy or the development of cardiovascular disease endpoints. The development of hyperkalemia with dual RAAS blockade is animportant potential side effect that must be monitored.

For most patients with diabetes, hypertension, and nephropathy, more thanone drug is necessary to control hypertension, the target being <130/80mmHg. Generally, an ACE inhibitor or an ARB is thought to be the best firstdrug in such patients. A diuretic usually is added as a second drug to helpthose who have sodium retention with increased blood volume. Once a third drugis necessary, almost any well-tolerated antihypertensive can be added.Combination therapy with both an ACE inhibitor and an ARB may be specificallyindicated in the setting of continued proteinuria despite maximal therapy withone of the agents and/or heart failure.

Footnotes

Mark E. Molitch, MD, is professor of medicine in the Division ofEndocrinology, Metabolism, and Molecular Medicine at Northwestern University'sFeinberg School of Medicine in Chicago.

References

1. Mogensen CE, Neldam S, Tikkanen I, et al.: Randomised controlledtrial of dual blockade of renin-angiotensin system in patients withhypertension, microalbuminuria, and non-insulin dependent diabetes: TheCandesartan and Lisinopril Microalbuminuria (CALM) study.BMJ 321:1440–1444, 2000.[Abstract/Free Full Text]

2. Jacobsen P, Andersen S, Rossing K, et al.: Dual blockade of therenin-angiotensin system in type 1 patients with diabetic nephropathy.Nephrol Dial Transplant 17:1019–1024, 2002.[Abstract/Free Full Text]

3. Rossing K, Jacobsen P, Pietraszek L, et al.: Renoprotective effectsof adding angiotensin II receptor blocker to maximal recommended doses of ACEinhibitor in diabetic nephropathy: A randomized double-blind crossover trial.Diabetes Care 26:2268–2274, 2003.[Abstract/Free Full Text]

4. Cohn JN, Tognoni G, for the Valsartan Heart Failure TrialInvestigators: A randomized trial of the angiotensin-receptor blockervalsartan in chronic heart failure. N Engl J Med 345: 1667–1675, 2001.[Abstract/Free Full Text]

5. McMurray JJ, Ostergren J, Swedberg K, et al., for the CHARMInvestigators and Committees: Effects of candesartan in patients with chronicheart failure and reduced left-ventricular systolic function takingangiotensin-converting-enzyme inhibitors: The CHARM-Added trial.Lancet 362:767–771, 2003.[Medline]

CiteULike

Del.icio.us

Digg

Reddit

Technorati

Services Email this article to a friend Similar articles in this journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                What's this?