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Review
. 2013 Oct 24;347:f6008.
doi: 10.1136/bmj.f6008.

Comparative Effectiveness of Renin-Angiotensin System Blockers and Other Antihypertensive Drugs in Patients With Diabetes: Systematic Review and Bayesian Network Meta-Analysis

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Free PMC article
Review

Comparative Effectiveness of Renin-Angiotensin System Blockers and Other Antihypertensive Drugs in Patients With Diabetes: Systematic Review and Bayesian Network Meta-Analysis

Hon-Yen Wu et al. BMJ. .
Free PMC article

Abstract

Objective: To assess the effects of different classes of antihypertensive treatments, including monotherapy and combination therapy, on survival and major renal outcomes in patients with diabetes.

Design: Systematic review and bayesian network meta-analysis of randomised clinical trials.

Data sources: Electronic literature search of PubMed, Medline, Scopus, and the Cochrane Library for studies published up to December 2011.

Study selection: Randomised clinical trials of antihypertensive therapy (angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), α blockers, β blockers, calcium channel blockers, diuretics, and their combinations) in patients with diabetes with a follow-up of at least 12 months, reporting all cause mortality, requirement for dialysis, or doubling of serum creatinine levels.

Data extraction: Bayesian network meta-analysis combined direct and indirect evidence to estimate the relative effects between treatments as well as the probabilities of ranking for treatments based on their protective effects.

Results: 63 trials with 36,917 participants were identified, including 2400 deaths, 766 patients who required dialysis, and 1099 patients whose serum creatinine level had doubled. Compared with placebo, only ACE inhibitors significantly reduced the doubling of serum creatinine levels (odds ratio 0.58, 95% credible interval 0.32 to 0.90), and only β blockers showed a significant difference in mortality (odds ratio 7.13, 95% credible interval 1.37 to 41.39). Comparisons among all treatments showed no statistical significance in the outcome of dialysis. Although the beneficial effects of ACE inhibitors compared with ARBs did not reach statistical significance, ACE inhibitors consistently showed higher probabilities of being in the superior ranking positions among all three outcomes. Although the protective effect of an ACE inhibitor plus calcium channel blocker compared with placebo was not statistically significant, the treatment ranking identified this combination therapy to have the greatest probability (73.9%) for being the best treatment on reducing mortality, followed by ACE inhibitor plus diuretic (12.5%), ACE inhibitors (2.0%), calcium channel blockers (1.2%), and ARBs (0.4%).

Conclusions: Our analyses show the renoprotective effects and superiority of using ACE inhibitors in patients with diabetes, and available evidence is not able to show a better effect for ARBs compared with ACE inhibitors. Considering the cost of drugs, our findings support the use of ACE inhibitors as the first line antihypertensive agent in patients with diabetes. Calcium channel blockers might be the preferred treatment in combination with ACE inhibitors if adequate blood pressure control cannot be achieved by ACE inhibitors alone.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Summary of trial identification and selection
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Fig 2 Network of eligible treatment comparisons for outcomes of all cause mortality, end stage renal disease, and doubling of serum creatinine levels. For each pairwise comparison, the arrowhead points to class of antihypertensive treatment with lower risk in traditional random effects meta-analyses. Results of direct comparison are presented as summary odds ratio (95% confidence interval)/number of trials providing information. The result of a single trial is provided when traditional meta-analysis in a specific comparison is not feasible. Solid lines represent direct comparisons and dotted lines indirect comparisons. ACE=angiotensin converting enzyme; ARB=angiotensin receptor blocker; CCB=calcium channel blocker; NA=not applicable in direct comparison owing to zero events in both treatment arms
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Fig 3 Ranking of treatment strategies based on probability of their protective effects on outcomes of all cause mortality, end stage renal disease, and doubling of serum creatinine levels. Angiotensin receptor blocker (ARB) plus calcium channel blocker (CCB); ARB plus diuretic, and angiotensin converting enzyme (ACE) inhibitor plus ARB were not ranked owing to wide credible intervals
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Fig 4 Forest plot for results from bayesian network meta-analysis (solid squares) and those from traditional pairwise meta-analysis (blank squares) for outcomes of all cause mortality, end stage renal disease, and doubling of serum creatinine levels. Squares represent pooled estimates of odds ratio. Lines for 95% confidence intervals represent 95% credible intervals in bayesian network meta-analysis and 95% confidence intervals in traditional pairwise meta-analysis. The result of a single trial is provided as direct evidence when traditional meta-analysis in a specific comparison is not feasible. Angiotensin receptor blocker (ARB) plus calcium channel blocker (CCB), ARB plus diuretic, and angiotensin converting enzyme (ACE) inhibitor plus ARB were not plotted owing to unstable estimated effects and extremely wide credible intervals

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