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

Abstract

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.

Keywords: Angiotensin-converting enzyme (ACE) inhibitor; Bayesian network meta-analysis; all-cause death; angiotensin II receptor blocker (ARB); blood pressure (BP); cardiovascular events; chronic kidney disease (CKD); comparative effectiveness; hypertension; kidney failure; mortality; renal disease progression; renin angiotensin system (RAS) inhibition.