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Combination of ACE Inhibitor and ARB Offers Little Advantage for Renal Function

Monotherapy was more effective in preserving renal function.

In patients with baseline nephropathy, angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers (ARBs) reduce proteinuria and preserve renal function. Questions remain about whether the renal effects of ACE inhibitors and ARBs are equivalent, whether a combination of the two classes are more effective than either one alone, and whether either class prevents loss of renal function in patients without nephropathy.

With funding from the manufacturer of telmisartan, researchers randomized 25,620 patients with atherosclerotic disease or advanced diabetes to receive telmisartan (80 mg daily), ramipril (10 mg daily), or both for a median of 56 months. Only 13% of patients had baseline albuminuria. Rates of the primary composite cardiovascular outcome were equivalent for telmisartan alone and ramipril alone, and combination treatment caused more adverse effects without added benefit than either drug alone (JW Apr 17 2008).

In a secondary analysis of renal effects, rates of dialysis or doubling of serum creatinine were similar with telmisartan (2.21%) and ramipril (2.03%) and slightly but significantly more common with combination treatment (2.49%). In most subgroups, patients in the combination and monotherapy groups reached renal endpoints at similar rates, but patients without diabetes or hypertension experienced significantly more events with combination therapy. Patients who received combination therapy had less progression of albuminuria than those who received either agent alone.

Comment: In this population, telmisartan and ramipril monotherapy had similar effects on albuminuria and renal function. Combination therapy seems more effective than monotherapy in reducing albuminuria, but less effective in the more important endpoint of preserving renal function. Combination therapy therefore seems to offer little advantage and possibly greater risk.

— Bruce Soloway, MD

Published in Journal Watch General Medicine September 2, 2008

Citation(s):

Mann JFE et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): A multicentre, randomised, double-blind, controlled trial. Lancet 2008 Aug 16; 372:547.

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