Renin angiotensin system blockade and cardiovascular outcomes in patients with chronic kidney disease and proteinuria: a meta-analysis

Abstract

Objective: The role of renin angiotensin system (RAS) blockade in controlling hypertension and the positive impact on cardiovascular (CV) outcomes is well known. However, the role of RAS blockade in improving CV outcomes in patients with chronic kidney disease (CKD) is still unclear.

Methods: Randomized controlled trials that analyzed CV outcomes in patients with CKD/proteinuria treated with RAS blockade (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) were included in our study. The relative risk across all study groups was computed using Mantel-Hanszel random effects model. Results were calculated with 95% CI and was considered statistically significant if 2-sided alpha error was <.05. Renin angiotensin system blockade-based therapy was compared with placebo and control (beta-blocker, calcium-channel blockers and other antihypertensive-based therapy) therapy in the study.

Results: Twenty-five trials (N = 45758) were used for analysis. Renin angiotensin system blockade decreased the risk for heart failure in patients with diabetic nephropathy when compared with placebo 0.78 (95% CI 0.66-0.92, P = .003) and control therapy (0.63, 95% CI 0.47-0.86, P = .003). The risk for CV outcomes was decreased with RAS blockade (0.56, 95% CI 0.47-0.67, P < .001) in nondiabetic nephropathy patients with CKD when compared with control therapy. There was also a significant reduction of CV outcomes (0.84, 95% CI 0.78-0.91, P < .0001), myocardial infarction (0.78, 95% CI 0.65-0.97, P = .03), and heart failure (0.74, 95% CI 0.58-0.95, P = .02) when we pooled all the patients with CKD and compared RAS blockade to placebo.

Conclusions: A pooled analysis of all causes of CKD revealed a reduction in the risk for myocardial infarction, heart failure, and total CV outcomes when RAS blockade was compared with placebo. RAS blockade decreases the risk for CV outcomes and heart failure when compared with control therapy in patients with proteinuria. There were also benefits with RAS blockade in reducing the risk of CV outcomes and heart failure in patients with diabetic nephropathy when compared with placebo.