Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients with CKD: A Bayesian Network Meta-analysis of Randomized Clinical Trials

Background There is much uncertainty regarding the relative effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in populations with chronic kidney disease (CKD). Study Design Systematic review and Bayesian network meta-analysis. Setting & Population Patients with CKD treated with renin-angiotensin system (RAS) inhibitors. Selection Criteria for Studies Randomized trials in patients with CKD treated with RAS inhibitors. Predictor ACE inhibitors and ARBs compared to each other and to placebo and active controls. Outcome Primary outcome was kidney failure; secondary outcomes were major cardiovascular events, all-cause death. Results 119 randomized controlled trials (n = 64,768) were included. ACE inhibitors and ARBs reduced the odds of kidney failure by 39% and 30% (ORs of 0.61 [95% credible interval, 0.47-0.79] and 0.70 [95% credible interval, 0.52-0.89]), respectively, compared to placebo, and by 35% and 25% (ORs of 0.65 [95% credible interval, 0.51-0.80] and 0.75 [95% credible interval, 0.54-0.97]), respectively, compared with other active controls, whereas other active controls did not show evidence of a significant effect on kidney failure. Both ACE inhibitors and ARBs produced odds reductions for major cardiovascular events (ORs of 0.82 [95% credible interval, 0.71-0.92] and 0.76 [95% credible interval, 0.62-0.89], respectively) versus placebo. Comparisons did not show significant effects on risk for cardiovascular death. ACE inhibitors but not ARBs significantly reduced the odds of all-cause death versus active controls (OR, 0.72; 95% credible interval, 0.53-0.92). Compared with ARBs, ACE inhibitors were consistently associated with higher probabilities of reducing kidney failure, cardiovascular death, or all-cause death. Limitations Trials with RAS inhibitor therapy were included; trials with direct comparisons of other active controls with placebo were not included. Conclusions Use of ACE inhibitors or ARBs in people with CKD reduces the risk for kidney failure and cardiovascular events. ACE inhibitors also reduced the risk for all-cause mortality and were possibly superior to ARBs for kidney failure, cardiovascular death, and all-cause mortality in patients with CKD, suggesting that they could be the first choice for treatment in this population.