Evidence of the Month

1. Evidence of the Month Comment on: Combination therapy with an ACE inhibitor and an angiotensin receptor blocker for diabetic nephropathy: a meta-analysis

2. Methods/primary outcome

3. Rationale for combination therapy Several studies suggest that dual RAAS blockade therapy provides a synergistic effect in diabetic nephropathy Single-drug therapy leads to incomplete blockade of the RAAS (�ACE escape�) ARBs reduce the damaging effects from production of angiotensin II by non-ACE pathways, which is not completely blocked by an ACE inhibitor Unlike ARBs, ACE inhibitors increase the half-life of bradykinin Thus, it seems plausible that combining an ACE inhibitor and an ARB could more effectively oppose the RAAS than either agent alone

4. Results

5. Clinical implications Short-term (8 to 12 weeks) combination therapy with ACE inhibitor + ARB is superior to ACE inhibitor alone in reducing 24-hour urinary protein excretion Optimal anti-proteinuric doses of ACE inhibitor and ARB not yet established, but recent studies indicate that higher doses are superior to lower doses Although a decrease in glomerular filtration rate was considered a transient effect, a decrease of nearly 4 ml/minute after 2 to 3 months of combination therapy should be considered in assessing risk/benefit of this treatment Additional studies evaluating accepted clinical end points, such as doubling of serum creatinine and onset of end-stage renal disease, are needed to establish the long-term benefit of combination therapy