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Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult
Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses
#MMPMID26954482
Catalá-López F
; Macías Saint-Gerons D
; González-Bermejo D
; Rosano GM
; Davis BR
; Ridao M
; Zaragoza A
; Montero-Corominas D
; Tobías A
; de la Fuente-Honrubia C
; Tabarés-Seisdedos R
; Hutton B
PLoS Med
2016[Mar]; 13
(3
): e1001971
PMID26954482
show ga
BACKGROUND: Medications aimed at inhibiting the renin-angiotensin system (RAS)
have been used extensively for preventing cardiovascular and renal complications
in patients with diabetes, but data that compare their clinical effectiveness are
limited. We aimed to compare the effects of classes of RAS blockers on
cardiovascular and renal outcomes in adults with diabetes. METHODS AND FINDINGS:
Eligible trials were identified by electronic searches in PubMed/MEDLINE and the
Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014).
Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors,
angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The
primary endpoints were cardiovascular mortality, myocardial infarction, and
stroke-singly and as a composite endpoint, major cardiovascular outcome-and
end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause
mortality-singly and as a composite endpoint, progression of renal disease.
Secondary endpoints were angina pectoris and hospitalization for heart failure.
In all, 71 trials (103,120 participants), with a total of 14 different regimens,
were pooled using network meta-analyses. When compared with ACE inhibitor, no
other RAS blocker used in monotherapy and/or combination was associated with a
significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR]
1.02; 95% credible interval [CrI] 0.90-1.18), ACE inhibitor plus ARB (0.97; 95%
CrI 0.79-1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96-1.81), and DR
inhibitor plus ARB (1.00; 95% CrI 0.73-1.38). For the risk of progression of
renal disease, no significant differences were detected between ACE inhibitor and
each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90-1.40), ACE inhibitor
plus ARB (0.97; 95% CrI 0.72-1.29), DR inhibitor plus ACE inhibitor (0.99; 95%
CrI 0.65-1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78-1.84). No
significant differences were showed between ACE inhibitors and ARBs with respect
to all-cause mortality, cardiovascular mortality, myocardial infarction, stroke,
angina pectoris, hospitalization for heart failure, ESRD, or doubling serum
creatinine. Findings were limited by the clinical and methodological
heterogeneity of the included studies. Potential inconsistency was identified in
network meta-analyses of stroke and angina pectoris, limiting the conclusiveness
of findings for these single endpoints. CONCLUSIONS: In adults with diabetes,
comparisons of different RAS blockers showed similar effects of ACE inhibitors
and ARBs on major cardiovascular and renal outcomes. Compared with monotherapies,
the combination of an ACE inhibitor and an ARB failed to provide significant
benefits on major outcomes. Clinicians should discuss the balance between
benefits, costs, and potential harms with individual diabetes patients before
starting treatment. REVIEW REGISTRATION: PROSPERO CRD42014014404.
|Adult
[MESH]
|Angina Pectoris/prevention & control
[MESH]
|Angiotensin Receptor Antagonists/*therapeutic use
[MESH]
|Angiotensin-Converting Enzyme Inhibitors/*therapeutic use
[MESH]
|Cardiovascular Diseases/mortality/*prevention & control
[MESH]
|Diabetes Complications/*prevention & control
[MESH]
|Diabetes Mellitus/*drug therapy
[MESH]
|Heart Failure/prevention & control
[MESH]
|Hospitalization
[MESH]
|Humans
[MESH]
|Kidney Failure, Chronic/*prevention & control
[MESH]
|Myocardial Infarction/prevention & control
[MESH]
|Renal Insufficiency, Chronic/prevention & control
[MESH]
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