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

doi:10.1016/j.ahj.2008.01.031

American Heart Journal

Volume 155, Issue 5, May 2008, Pages 791-805

https://doi.org/10.1016/j.ahj.2008.01.031 Get rights and content

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 α error was <.05. Renin angiotensin system blockade–based therapy was compared with placebo and control (β-blocker, calcium-channel blockers and other antihypertensive-based therapy) therapy in the study.

Results

Twenty-five trials (N = 45 758) 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.

Section snippets

Methods

Standardized protocol was used to identify the data for our analysis.

Results

Initial search resulted in 1142 studies. Redundant studies in the different search methods were considered only once for the meta-analysis. Of these, 62 studies were selected for detailed review. Eleven studies were excluded as the data were repeated from previously published studies. Seventeen studies were excluded as there were no data available on CV outcomes. Five studies were excluded as there was no active comparison, and 4 trials were excluded for not describing the CV outcomes based on

Discussion

Chronic kidney disease and protienuria have been associated with adverse CV outcomes due to multiple factors. Chronic kidney disease patients have increased risk for CV disease due to the coexisting proatherogenic risk factors that include diabetes mellitus, hypertension, and dyslipedemia. Proteinuria is an independent risk factor for the occurrence of adverse cardiovascular outcomes. Renal replacement therapy might further increase the risk for adverse events owing to its proinflammatory

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Curriculum in CardiologyRenin angiotensin system blockade and cardiovascular outcomes in patients with chronic kidney disease and proteinuria: A meta-analysis

Objective

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Am J Kidney Dis

Kidney Int

Am J Kidney Dis

Kidney Int

Kidney Int

Am J Kidney Dis

Kidney Int

Kidney Int

Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators

N Engl J Med

Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS)

N Engl J Med

Beyond blood pressure: new roles for angiotensin II

Cell Mol Life Sci

Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques: potential implications for inflammation and plaque instability

Circulation

Proteinuria: value as predictor of cardiovascular mortality in insulin dependent diabetes mellitus

Br Med J (Clin Res Ed)

A ten-year prospective study, 1964-1974, of cardiovascular risk factors in men and women from the Glostrup population born in 1914. Multivariate analyses

Dan Med Bull

ACE inhibition reduces proteinuria in normotensive patients with IgA nephropathy: a multicentre, randomized, placebo-controlled study

Nephrol Dial Transplant

Cardiovascular outcomes in high-risk hypertensive patients stratified by baseline glomerular filtration rate

Ann Intern Med

Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study)

BMJ

Are angiotensin converting enzyme inhibitors superior to beta blockers in retarding progressive renal function decline?

Kidney Int Suppl

Randomised controlled trial of enalapril and beta blockers in non-diabetic chronic renal failure

BMJ

Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group

N Engl J Med

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