Efficacy and Safety of Combined vs. Single Renin-Angiotensin-Aldosterone System Blockade in Chronic Kidney Disease: A Meta-Analysis

• Published in: American journal of hypertension Vol. 26; no. 3; pp. 424 - 441
• Main Authors: Susantitaphong, Paweena, Sewaralthahab, Kamal, Balk, Ethan M., Eiam-ong, Somchai, Madias, Nicolaos E., Jaber, Bertrand L.
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01-03-2013
• Series: Editor's choice
• Subjects: Adult; Aged; Albuminuria - drug therapy; Angiotensin Receptor Antagonists - administration & dosage; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Blood Pressure - drug effects; Clinical trials; Cross-Over Studies; Drug therapy; Glomerular Filtration Rate - drug effects; Humans; Hyperkalemia - chemically induced; Hypotension - chemically induced; Kidney diseases; Middle Aged; Mineralocorticoid Receptor Antagonists - administration & dosage; Mortality; Original; Proteinuria - drug therapy; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic - drug therapy; Renin - antagonists & inhibitors; Renin-Angiotensin System - drug effects; hypotension; RAAS blockade; blood pressure; chronic kidney disease; GFR; potassium; proteinuria; Combined; hypertension; randomized controlled trial
• ISSN: 0895-7061; 1941-7225
• DOI: 10.1093/ajh/hps038

BACKGROUND
Although dual blockade of the renin-angiotensin-aldosterone system (RAAS) has gained popularity for the treatment of kidney disease, its benefits and potential risks have not been fully elucidated. We conducted a meta-analysis of all randomized controlled trials comparing the efficacy and safety of combined vs. single RAAS blockade therapy in chronic kidney disease (CKD).
METHODS
We performed a literature search using MEDLINE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, scientific abstracts from meetings, and bibliographies of retrieved articles. We used random-effects models to compute net changes and rate differences in variables.
RESULTS
Fifty-nine (25 crossover and 34 parallel-arm) randomized controlled trials (RCTs) comparing the efficacy and safety of combined vs. single RAAS blockade therapy in CKD were identified (4,975 patients). Combined RAAS blockade therapy was associated with a significant net decrease in glomerular filtration rate (GFR) (-1.8ml/min or ml/min/1.73 m2; P = 0.005), albuminuria (-90mg/g of creatinine; P = 0.001 or -32mg/day; P = 0.03), and proteinuria (-291mg/g; P = 0.003 or -363mg/day; P < 0.001). Combined RAAS blockade therapy was associated with a 9.4% higher rate of regression to normoalbuminuria and a 5% higher rate of achieving the blood pressure (BP) goal (as defined in individual trials). However, combined RAAS blockade therapy was associated with a significant net increase in serum potassium level, a 3.4% higher rate of hyperkalemia, and a 4.6% higher rate of hypotension. There was no effect on doubling of the serum creatinine level, hospitalization, or mortality.
CONCLUSIONS
Although combined RAAS blockade therapy in CKD is associated with a decrease in albuminuria and proteinuria, it is associated with a decrease in GFR and a higher incidence of hyperkalemia and hypotension relative to monotherapy. The potential long-term kidney benefits of combined RAAS blockade therapy require further study.