Orly Kohn, MD
In patients with renal disease, do angiotensin-receptor blockers (ARBs) reduce proteinuria more than placebo, other antihypertensive drugs, or their combinations?
Articles selected compared ARBs with placebo, angiotensin-converting enzyme inhibitors (ACE-Is), or other antihypertensive drugs in patients with renal disease and microalbuminuria or proteinuria. Studies that compared a combination of ARBs and ACE-Is with either drug alone were also included. Dose comparison studies or those in patients having renal transplantation or normal urinary protein excretion were excluded. Outcomes were albuminuria or proteinuria, and adverse effects.
MEDLINE (1990 to September 2006); Cochrane Central Register of Controlled Trials (Issue 3, 2006); and reference lists of relevant articles were searched for English-language, randomized, controlled trials (RCTs) with ≥ 10 patients per group, ≥ 4-week duration, and changes in urinary protein excretion as an outcome. Experts were consulted. 49 RCTs (n = 6181; mean follow-up range 1 to 12 mo; mean age range 25 to 64 y for 43 RCTs) were included. 1 eligible trial was excluded for methodological concerns. 18 of 21 crossover trials had prolonged washout periods between treatments or found no carryover effect. 7 RCTs met 3 quality criteria (concealed allocation, blinding, and intention-to-treat analysis), 27 met 1 or 2, and 15 met none.
Meta-analysis showed that monotherapy with ARBs reduced proteinuria more than placebo and calcium-channel blockers (CCBs) but not ACE-Is (Table). An ARB combined with an ACE-I reduced proteinuria more than either drug alone at 1 to 4 months (Table). Adverse effects were inconsistently reported.
In patients with renal disease, ARBs and ACE-Is do not differ for reducing proteinuria. A combination of both drugs is more effective than either drug alone.
Angiotensin-receptor blockers (ARBs) to reduce proteinuria in renal disease*
*ACE-I = angiotensin-converting enzyme inhibitor; other abbreviations defined in Glossary. A random-effects model was used.
†Ratio of means < 1 favors ARB in monotherapy comparisons and combination therapy in other comparisons.
‡Significant heterogeneity (I2 > 50%).
§Revised data, including the 1999 Muirhead study, provided by the author.
Kohn O. Review: Combination therapy with renin-angiotensin inhibitors reduces proteinuria more than single drugs alone in renal disease. Ann Intern Med. ;148:JC4–8. doi: 10.7326/0003-4819-148-12-200806170-02008
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Published: Ann Intern Med. 2008;148(12):JC4-8.
Nephrology, Urological Disorders.
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