Efficacy and safety of combined vs. single renin-angiotensin-aldosterone system blockade in chronic kidney disease: a meta-analysis - PubMed (original) (raw)
Meta-Analysis
Efficacy and safety of combined vs. single renin-angiotensin-aldosterone system blockade in chronic kidney disease: a meta-analysis
Paweena Susantitaphong et al. Am J Hypertens. 2013 Mar.
Abstract
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 m(2); 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.
Figures
Figure 1.
Flow diagram for selection of studies of combined vs. single-agent blockade of the renin–angiotensin–aldosterone system (RAAS) included in the meta-analysis.
Figure 2.
Distribution of combined renin–angiotensin–aldosterone system (RAAS) blockade therapies. Abbreviations: ACEI, Angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor type-2 blocker; ARA, aldosterone receptor antagonist; DRI, direct renin inhibitor.
Figure 3.
Subgroup analyses displaying the effect of combined renin–angiotensin–aldosterone system (RAAS) blockade therapy on standardized net change in albuminuria (A) and standardized net change in proteinuria (B). Where shown, P values refer to subgroup comparisons.
Figure 3.
Subgroup analyses displaying the effect of combined renin–angiotensin–aldosterone system (RAAS) blockade therapy on standardized net change in albuminuria (A) and standardized net change in proteinuria (B). Where shown, P values refer to subgroup comparisons.
Figure 4.
Subgroup analyses displaying the effect of combined renin–angiotensin–aldosterone system (RAAS) blockade therapy on standardized net change in GFR (A), and the summary rate difference in the development of hyperkalemia (B), and hypotension (C). Where shown, P values refer to subgroup comparisons.
Figure 4.
Subgroup analyses displaying the effect of combined renin–angiotensin–aldosterone system (RAAS) blockade therapy on standardized net change in GFR (A), and the summary rate difference in the development of hyperkalemia (B), and hypotension (C). Where shown, P values refer to subgroup comparisons.
Figure 4.
Subgroup analyses displaying the effect of combined renin–angiotensin–aldosterone system (RAAS) blockade therapy on standardized net change in GFR (A), and the summary rate difference in the development of hyperkalemia (B), and hypotension (C). Where shown, P values refer to subgroup comparisons.
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