ACE inhibitors reduce all-cause mortality in diabetic nephropathy; data unclear for AIIRAs

A meta-analysis demonstrates that angiotensin converting enzyme (ACE) inhibitors provide a survival benefit in patients with diabetic nephropathy, whereas no such evidence exists for angiotensin II receptor antagonists (AIIRAs). Both classes of drugs prevent progression of nephropathy and promote regression to normoalbuminuria.

The meta-analysis included almost exclusively placebo-controlled trials, making comparison of the relative effects of ACE inhibitors and AIIRAs on survival difficult, according to the study authors. "True differences in the relative effects of ACE inhibitors and AIIRAs can be established only by adequately powered trials that directly compare the two agents, which unfortunately are not available," they write.

Forty-three trials in which ACE inhibitors or AIIRAs were compared with placebo or each other in patients with micro- or macroalbuminuria were identified through a search of Medline, Embase, and a renal group trial register. Thirty-six trials compared ACE inhibitors with placebo (N=4,008), 4 compared AIIRAs with placebo (N=3,331), and 3 compared ACE inhibitors with AIIRAs (N=206). Additional study data were obtained from study authors, when possible, to evaluate all outcomes of interest (eg, all-cause death and renal outcomes).

Compared with placebo, ACE inhibitors were associated with reductions in a doubling of serum creatinine concentration and the development of end-stage renal disease, which approached but did not achieve significance. ACE inhibitors significantly reduced the risk of progression from micro- to macroalbuminuria by 55% (95% CI, 0.28–0.71) and significantly increased the rate of regression from micro- to normoalbuminuria by more than 3-fold (RR=3.42; 95% CI, 1.95–5.99).

Three trials in which AIIRAs were compared with placebo showed a significant 22% reduction in the risk of end-stage renal disease (95% CI, 0.67–0.91) and a significant 21% reduction in the risk of doubling of serum creatinine (95% CI, 0.67–0.93) with AIIRAs. Three placebo-controlled trials also demonstrated a significant 51% decrease in the risk of progression from micro- to macroalbuminuria with therapy (95% CI, 0.32–0.75), and 2 trials showed a significant increase in the rate of regression from micro- to normoalbuminuria (RR=1.42; 95% CI, 1.05–1.93).

The 3 trials in which ACE inhibitors were compared with AIIRAs did not report on all-cause mortality, end-stage renal disease, or doubling of serum creatinine; in 1 trial, a trend existed favoring ACE inhibitors in reducing the risk of progression from micro- to macroalbuminuria (RR=0.16; 95% CI, 0.02–1.44).

The effect of ACE inhibitors on all-cause mortality did not vary according to type of diabetes, presence or absence of hypertension, or microalbuminuria compared with macroalbu-minuria at baseline.

The authors concluded that the designs of the trials, including the patient populations studied, their risk of renal disease at baseline, and achieved blood pressure differences compared with placebo, may explain some of the differences observed in the results between the 2 classes of agents.

SOURCE Strippoli GFM, Craig M, Deeks JJ, Schena FP, Craig JC. Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review. BMJ [serial online]. October 2004;329:1-12. Available from BMJ Publishing Group, Limited, London, England. Accessed February 23, 2005.