A systematic meta-analysis 3 included 26 RCTs - including 20 for angiotensin-converting enzyme inhibitors (ACE inhibitors) and 6 for angiotensin II receptor blockers (ARBs) - with a total of 10 378 diabetic patients with microalbuminuria. Compared with placebo, ARBs significantly reduced the risk of end stage renal disease (ESRD) by 23% (odds ratio 0.77, 95% CI 0.65 to 0.92), while ACE inhibitors showed a trend towards decreased risk of ESRD (OR 0.69, 0.43 to 1.10). Both ACE inhibitors and ARBs reduced the risk of doubling of the serum creatinine level (OR 0.60, 0.39 to 0.91 for ACE inhibitors; OR 0.75, 0.64 to 0.88 for ARBs), and subgroup analyses for patients with macroalbuminuria or microalbuminuria showed similar results.
Another systematic review with network meta-analyses 4 assessing renal outcomes of renin-angiotensin system blockade in adults with diabetes (with or without proteinuria) included 71 trials with 103 120 participants. For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARBs (OR 1.10; 95% CI 0.90 to 1.40), ACE inhibitor plus ARB (0.97; 95% CI 0.72 to 1.29), direct renin (DR) inhibitor plus ACE inhibitor (0.99; 95% CI 0.65 to 1.57), and DR inhibitor plus ARB (1.18; 95% CI 0.78 to 1.84). No significant differences were showed between ACE inhibitors and ARBs with respect to all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, hospitalization for heart failure, ESRD, or doubling serum creatinine. Findings were limited by the clinical and methodological heterogeneity of the included studies.
A Cochrane review [Abstract] 5 included 109 RCTs with a total of 28 341 participants. Overall, the risk of bias was high. Compared to placebo or no treatment, ACEi or ARB made no difference to all-cause death. ACEi prevented kidney failure (RR 0.61, 95% CI 0.39 to 0.94; 8 studies, n=6643: I²= 0%). ARB prevented kidney failure (RR 0.82, 95% CI 0.72 to 0.94; 3 studies, n=3227: I² = 0%), doubling of serum creatinine (RR 0.84, 95% CI 0.72 to 0.97; 4 studies, n=3280: I² = 32), and the progression from microalbuminuria to microalbuminuria (RR 0.44, 95% CI 0.23 to 0.85; 5 studies, n=815: I² = 74%).
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