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DOI:10.3969/j.issn.1672-7347.2013.06.012
http://xbyx.xysm.net/xbwk/fileup/PDF/201306623.pdf

ACEI ARB Meta


123
(1. 2120022. 610031
3. 212001)

[ ] ( ACEI) II (ARB)
CoChrane PubMedEmbase
Revman 5.1 11 (RCTs) 602 Meta ACEI ACEI
ARB 24 h 24 h 24 h
ARB ACEI ARB ACEI ARB ACEI
ARB 24 h ACEI
ARB
ACEI ARB
[ ] II Meta

Meta analysis of the efficacy and safety of combined


treatment with ARB and ACEI on
diabetic kidney disease
GU Jinjin1, HAN Lina2, LIU Qiang3
(1. Department of Gerontology, Zhenjiang First Peoples Hospital, Zhenjiang Jiangsu 212002;
2. Department of Endocrinology and Metabolism, Third People's Hospital of Chengdu, Chengdu 610031;
3. Clinical Laboratory, the Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212001, China)

ABSTRACT Objective: To evaluate the efficacy and safety of combined treatment with angiotensin II

receptor blocker (ARB) and angiotensin converting enzyme inhibitor ( ACEI) on diabetic
kidney disease.
Methods: Randomized controlled trials (RCTs) were identified from CoChrane library, PubMed,

(Date of reception)2012-06-04
(Biography)
(Corresponding author)Email: liuqiang_free@163.com
(Foundation item)2012(JLY20120169) This work was supported by the Clinical Science and Technology
Fundation in 2012 of Jiangsu University, P. R. China (JLY20120169).

624

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EMbase, CNKI and VIP. Eleven RCTs involving 602 patients were included and analyzed with Rev
Man 5.1 software.
Results: Compared with ACEI alone, combined treatment with ARB and ACEI was more effective
on decreasing 24 h albuminuria, systolic pressure, average 24 h systolic pressure, diastolic pressure,
and average 24 h diastolic pressure but with a high level of serum potassium. Compared with ARB
alone, combined treatment with ARB and ACEI was more effective on decreasing systolic pressure
and diastolic pressure. Compared with ACEI or ARB alone, we didnt get a definite conclusion
that whether combined treatment with ARB and ACEI was more effective on decreasing 24 h
proteinuria.
Conclusion: Based on this Meta analysis, combined treatment with ARB and ACEI is safer and
has positive effect on diabetic kidney disease. However, small sample size and low methodological
quality appeared in most of the trials included in this systematic review. Therefore, available
evidence is insufficient to recommend a routine clinical application of combined treatment with
ARB and ACEI on diabetic kidney disease.
KEY WORDS

ACEI; ARB; diabetic kidney disease; Meta analysis

(diabetic kidney diseaseDKD


diabetic nephropathyDN)(DM)

(end stage renal diaease


ESRD) [1] DKD
[2]
[3-4] --
(renin angiotensin aldosterone systemRAAS)
DKD
RAAS
(angiotensin converting enzyme inhibitorACEI)
II (angiotensin II receptor
blockerARB)ACEIACEAng
I Ang II Ang II ARB
Ang II 1(type 1 receptorAT1)
Ang II RAAS
Barnett [5]DKD
ACEIARB2012
(KDOQI)

ACEIARB
(/30~300 mg/g)
ACEIARBDKD
ACEIARB

ACEIARBDKD
CocharaneACEIARB
DKD(randomized controlled
trialsRCTs)Meta

1
1.1
1.1.1
ACEIARBDKD
()

1.1.2
DKD
(/>300 mg/g
>200 g/min>300 mg/d>0.5
g/d)

1.1.3
ACEIARB
ACEIARBACEI+
A R B + ACE I A R B

1.2
1966120123
ACEIARBDKD

(CNKI1979120123)
(VIP1989120123)
1)ACEIA R B
II

ACEI ARB Meta

OR 2)
OR3)
OR
1)2)3)AND
PubMed(196620123)Embase(1974
2 0 1 2 3 ) Co C h r a n e ( 2 0 1 2 3
)1)ACEIARBangiotensin
converting enzyme inhibitorsangiotensin 1 receptor
blockerOR2)diabetic
nephrologydiabetic kidney disease
OR 3)dualcombination
OR1)2)3)AND

1.3
2

CoChraneHandbook 5.1

1.4
1.4.1
24 h24 h
(SBP)(DBP)24 h
(24 h SBP)24 h(24 h DBP)
II (Ang II )

1(TGF- 1)
1.4.2

1.5
CoChraneR ev man5.1
M e t a ( R D)
95%CI(MD)
(S M D) 9 5 % CI

( P 0.1 I 2 50%)
( P <0.1 I 2 >50%)

(95% CI)Cocharane
Handbook 5.1
MetalnMD(95% CI)
lnSMD(95% CI)

625

2
2.1
340(260
80)Endnote
5.0
28357
DKD31
DKDDKD3
1
4(
)1 [6] 4
13 [6-18] [6]
DKD24 h>300 mg/d
80~2628 mg/d
[18]6766

11(7 [7-13] 4
[14-17] )60224
5
1
114 [7-10]
74[7-10]
7
6 [7-11,13] 5
6 [7,9,11-13,15]
5[15]5[12]2[9]5[11]1[7]4[13]

3[14-15,17]

2.2
2.2.1
2.2.1.1 24 h
ACEI+ARBvs ACEI7 [11-17]
[12] 24 h(95%
CI)MetalnSMD (95% CI)=0.15
(0.570.86)SMD (95% CI)=1.16 (0.572.36)
P= 0.6924 h
6 [11,13-17]
2
(I =95%P<0.001)

24 h
1.85 g[SMD (95% CI)=1.85 (2.980.71)
P= 0.001]

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626

1 Meta
Table 1 Main characteristics of clinical trials included in the Meta analysis
/

() DM/
Rossing K
2002

T2DM

18(13)

136

588

20 mg/d 20 mg/d

[7]*

/
2

20 mg/d 20 mg/d
100 mg/d+ 100 mg/d+
8 mg/d

Rossing K
2003

T2DM

20(17)

158

628

40 mg/d 40 mg/d

[8]*

40 mg/d 40 mg/d
150 mg/d+ 150 mg/d+
16 mg/d

Titan SM

T2DM

56(35)

>5

2011[11]

ACEI+ARB 40 mg/d +

40 mg/d +

58.110.8

100 mg/d

8 mg/d +

8 mg/d

300 mg/d

300 mg/d

ACEI+
599.8
Matos JP

T2DM

20(5)

1114.07

5424.4

2005[12]*
Jacobsen P

T1DM

21(17)

298

4510

20 mg/d 20 mg/d

2002[9]*

4
2

20 mg/d 20 mg/d
100 mg/d + 100 mg/d+

Jacobsen P
2003

Song JH
2006

24(17)

319

429

T2DM

25(11)

83

488

T2DM

60()

>5

50.42.2

[13]*

2007

T1DM

[10] *

[14]

DM

90(46)

39~70

40 mg/d+

40 mg/d+

300 mg/d

5 mg/d+

10 mg/d

8 mg/d

16 mg/d

10 mg/d +

10 mg/d

150 mg/d

150 mg/d

2
4
2
6

80~160 mg/d 80~160 mg/d


DM

178(80) ACEI+ARB ACEI+ARB 10 mg/d +

2011[16]

10~20 mg/d + 10~20 mg/d

2007[15]

2009

300 mg/d

[17]

T2DM

90(46)

128

647ACEI

ACEI/ARB

647

137

ARB646

64

80 mg/d

80 mg/d

80 mg/d

10 mg/d +

10-20 mg/d

80 mg/d

80-160 mg/d

T1DM1T2DM2

ACEI+ARBvs ARB6 [12-17]


[12] 2 4 h ( 9 5 %
CI)MetaInSMD(95%CI)=0.18
(0.900.54)SMD(95% CI)=0.84 (0.411.72)
P= 0.6224 h
5 [13-17]
2
( I = 9 5 % P< 0 . 0 0 1 )

24 h
1.91 g[SMD=1.9195%CI (3.130.69)
P= 0.002]

2.2.1.2 24 h
4 [7-10] A C E I A R B
ACEI
2
(I =0P=0.96)

24 h0.53 g[MD=0.5395% CI
(1.010.42) P= 0.01]
2.2.1.3 (SBP)
ACEI+ARB vs ACEI6 [11-12,14-17]

2
( I = 39% P= 0.14)

ACEI ARB Meta

SBP
5.19 mmHg[MD=5.1995% CI (7.562.83)
P< 0.001]
A C E I + A R B v s A R B 5 [12,14-17]

2
(I =0P=0.78)
SBP
4.05 mmHg[MD=4.0595% CI (6.491.61)
P= 0.001]
2.2.1.4 (DBP)
ACEI+ARBvs ACEI6 [11-12,14-17]

2
( I = 67% P= 0.01)

DBP3.46 mmHg[MD=3.4695% CI
(6.730.18)P=0.04]
ACEI+ARB vs ARB5 [12,14-17]

2
( I = 66% P= 0.02)

DBP3.22 mmHg[MD=3.2295%
CI (6.370.06) P= 0.05]
2.2.2
ACEIARB
Me t a A C E I A R B
ACE I 2
ACE I 2 4 h S B P 2 4 h D B P

627

A ng I ITGCHOLH DLHbA1c
H b TG F - 1
( P> 0.05)ACEIARB ARB
3ARB
24hSBP24hDBP TGCHOL
HbA1cTGF- 1
( P> 0.05)
2.2.3
8 [7,8-13,15,17]

3
[8,14,16]

ACEIARB ACEI
4 ACE I
(P<0.05)

( P> 0.05)ACEIARB ARB


5ARB

( P> 0.05)

2 ACEIARB ACEIDKD
Table 2 Comparison of secondary efficacy indices in the treatment of clinical DKD with ACEI +ARB vs ACEI

I2/%
P
MD(95% CI)
SMD(95% CI)
24 h SBP
6[7-10,12-13]
6
0.38

3.18(6.260.11)

24 h DBP
6[7-10,12-13]
0
0.85

2.75(4.740.77)

1[7]

11.00(8.2313.77

2[9-10]*
0
0.97

0.50(0.761.75)#

Ang II
2[7,9]
0
0.97

4.74(0.6210.10

TG
2[12,14]
0
0.97

0.03(0.440.50)
CHOL
5[8-10,12,14]
0
0.85

0.09(0.370.19)
HDL
2[10,12]
0
0.69

0.07(0.510.37)
HbA1c
6[7-10,12-13]
0
1.00

0.17(0.110.45)

Hb
2[9-10]
0
0.80

0.35(0.740.04)

4[9-10,12-13]
0
0.52

0.10(0.230.43)
TGF-1
2[12-13]
30
0.23

5.25(12.522.02)

(95%CI)# lnMD(95% CI)

P
0.04
0.007
<0.001
0.44
0.08
0.90
0.53
0.76
0.23
0.08
0.54
0.16

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628

3 ACEIARB ARBDKD
Table 3 Comparison of secondary efficacy indices in the treatment of clinical DKD with ACEI +ARB vs ARB

I /%

24 h SBP

[12-13]

0.69

24 h DBP

2[12-13]

0.83

TG

[12,14]

45

0.48

CHOL

2[12,14]

0.85

HbA1c

[12-13]

42

0.19

2[12-13]

29

0.24

[12-13]

0.33

TGF-1

MD (95% CI)

SMD (95% CI)

0.29 (4.614.03)

0.89

1.14 (4.241.96)

0.72

0.21(0.260.68)

0.38

0.09 (0.370.19)

0.53

0.26 (0.210.73)

0.28

0.10 (0.230.43)

0.54

3.93 (10.682.82)

0.25

4 ACEIARB ACEIDKD
Table 4 Comparison of safety in the treatment of clinical DKD with ACEI +ARB vs ACEI

[7-10,12-16]

[9-13,15,17]

1[9]*

[7-8,10,12-16]

9[7-13,15-16]
[7,9-10]

7[9-13,15,17]

I2/%

0.41

MD (95%CI)

RD (95%CI)

SMD (95%CI)

0.13(0.040.21)

0.004

0.84

0.05(0.030.12)

0.22

1.09(0.582.08)#

0.77

0.84

0.15(0.050.34)

0.13

1.00

1.43(3.881.02)

0.25

0.99

2.31(10.85622)

0.60

58

0.03

0.07(0.020.16)

0.14

(95%CI) lnSMD(95% CI)

5 ACEIARB ARBDKD
Table 5 Comparison of safety in the treatment of clinical DKD with ACEI +ARB vs ARB

I2/%
P
MD (95% CI)
RD (95% CI)
SMD (95% CI)
[12-16]

3[12-13,15]

67

0.02

0.10(0.130.32)

0.40

0.96

0.08(0.010.17)

0.08

0.21(0.020.45)

0.07

[12-16]

17

0.31

[12-13,15-16]

0.78

1.31(4.091.47)

0.35

4[12-13,15,17]

0.44

0.04(0.050.12)

0.38

3
DKD

DKD
DKD

7~10ACEIARB

DKD
DKD

ACEI
ACEIARB24 h
24 h24 h
ARB
ACEIARB
ACEIARBACEIARB
DKD24 h

ACEI ARB Meta

ACEIACEIARB
II

ACEIACEIARB

ARBACEIARB
24 h24 h

ACEI
ARB

(ongoing telmisartan alone and in combination with


ramipril global endpoint trialONTARGET) [19-20]
25620
(85%69%
38%)56
ARBACEI
(2.4/1.4 mmHg)
(
)

(
)
ONTARGET

()
ACEIARBDKD

1)
114
66

ACEIARBDKD2)
ACEIACEIARB
213(24 h
)
Meta3
3)ARBACEIARB

629

153(24 h
)
Meta3
4)24 h
[ (95%CI)
]Meta5)
DKD
()
ACEIARB
6)ACEIARB

ACEIARBDKD

ACEIARBDKD

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Meta [ J].
: , 2013, 38(6): 623-630. DOI:10.3969/
j.issn.1672-7347.2013.06.012
Cite this article as: GU Jinjin, HAN Lina, LIU Qiang. Meta analysis
of the efficacy and safety of combined treatment with ARB and
ACEI on diabetic kidney disease[ J]. Journal of Central South
University. Medical Science, 2013, 38(6): 623-630. DOI:10.3969/
j.issn.1672-7347.2013.06.012

( )