Atherosclerosis 216 (2011) 7–16
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Atherosclerosis
journal homepage: www.elsevier.com/locate/atherosclerosis
Review
Angiotensin converting enzyme inhibitors effect on endothelial dysfunction:
A meta-analysis of randomised controlled trials
Yousef Shahin
∗
, Junaid Alam Khan, Nehemiah Samuel, Ian Chetter
Academic Vascular Surgical Unit, Hull York Medical School & University of Hull, Hull, UK
article info
Article history:
Received 17 December 2010
Received in revised form 16 February 2011
Accepted 21 February 2011
Available online 26 February 2011
Keywords:
Flow mediated dilatation
Brachial FMD
Renin angiotensin system
Angiotensin converting enzyme inhibitors
Endothelial dysfunction
Endothelial function
abstract
Objective: Several studies have assessed the effect of angiotensin converting enzyme inhibitors (ACEIs)
on endothelial dysfunction as measured by brachial flow-mediated vasodilatation (FMD). We conducted
a meta-analysis to investigate this effect in comparison to placebo or no treatment and to other antihy-
pertensive agents.
Methods: MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched
from 1996 to October 2010 on randomised controlled trials (RCTs) that assessed the effect of ACEIs on
brachial FMD versus placebo or no treatment and ACEIs versus angiotensin receptor blockers (ARBs),
calcium channel blockers (CCBs) and -blockers. Data from included studies were pooled with use of
random effects meta-analysis of the weighted mean change differences between the comparator groups.
Heterogeneity across studies was assessed with the I
2
statistic.
Results: In 10 trials including 1129 patients, treatment with ACEIs (n = 498) versus placebo or no treat-
ment (n = 503) significantly improved brachial FMD (pooled mean change difference 1.26%, 95% C.I.
0.46–2.07, p = 0.002 with significant heterogeneity). In 11 trials which included 805 patients, treatment
with ACEIs (n = 264) had a significant effect on brachial FMD when compared with other antihyperten-
sives (ARBs, CCBs and -blockers) (n = 420) (pooled mean change difference 0.89%, 95% C.I. 0.22–1.56,
p = 0.009, I
2
= 83%, p for heterogeneity < 0.00001). In 7 trials, treatment with ACEIs had no significant
effect on FMD when compared with ARBs (pooled mean change difference = 0.21%, 95% C.I. -0.24 to 0.66,
p = 0.36, I
2
= 0%). However, in 4 trials ACEIs significantly improved FMD when compared with CCBs (pooled
mean change difference 2.15%, 95% C.I. 0.55–3.75, p = 0.009, I
2
= 90%, p for heterogeneity < 0.00001). When
compared with -blockers in 4 trials, ACEIs also had a significant effect on FMD (pooled mean change
difference = 0.59%, 95% C.I. 0.05–1.13, p = 0.03, I
2
= 34%, p for heterogeneity = 0.21).
Conclusions: This study shows that ACEIs improve brachial FMD which is a marker of endothelial function
in patients with endothelial dysfunction caused by various conditions and are superior to CCBs and
-blockers. There was no significant difference between ACEIs and ARBs effect on brachial FMD.
© 2011 Elsevier Ireland Ltd. All rights reserved.
Contents
1. Introduction .......................................................................................................................................... 8
2. Methods .............................................................................................................................................. 8
2.1. Search strategy ............................................................................................................................... 8
2.2. Inclusion criteria .............................................................................................................................. 8
2.3. Data extraction ............................................................................................................................... 8
2.4. Statistical analysis ............................................................................................................................ 8
2.5. Risk of bias .................................................................................................................................... 10
3. Results ................................................................................................................................................ 10
3.1. Literature search .............................................................................................................................. 10
3.2. Characteristics of patients and trials ......................................................................................................... 11
∗
Corresponding author at: Academic Vascular Surgical Unit, Vascular Laboratory, Hull Royal Infirmary, Anlaby Road, Hull HU3 2JZ, UK. Tel.: +44 1482674178;
fax: +44 1482674765.
E-mail address: yousef.shahin@yahoo.co.uk (Y. Shahin).
0021-9150/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.atherosclerosis.2011.02.044