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BMC Cardiovascular Disorders

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The difference between Asian and Western in the effect of LDL-C lowering therapy on coronary atherosclerotic plaque: a meta-analysis report

BMC Cardiovascular Disorders201515:6

https://doi.org/10.1186/1471-2261-15-6

Received: 16 September 2014

Accepted: 12 January 2015

Published: 14 February 2015

Abstract

Background

The different effects of LDL-C levels and statins therapy on coronary atherosclerotic plaque between Western and Asian remain to be settled.

Methods

PubMed, EMBASE, and Cochrane databases were searched from Jan. 2000 to Sep. 2014 for randomized controlled or blinded end-points trials assessing the effects of LDL-C lowering therapy on regression of coronary atherosclerotic plaque (CAP) in patients with coronary heart disease by intravascular ultrasound. The significance of plaques regression was assessed by computing standardized mean difference (SMD) of the volume of CAP between the baseline and follow-up.

Results

Twenty trials (ten in the West and ten in Asia) were identified. For Westerns, Mean lowering LDL-C by 49.4% and/or to level 61.9 mg/dL in the group of patients with baseline mean LDL-C 123.2 mg/dL could significantly reduce the volume of CAP at follow up (SMD −0.156 mm3, 95% CI −0.248 ~ −0.064, p = 0.001). LDL-C lowering by rosuvastatin (mean 40 mg daily) could significantly decrease the volumes of CAP at follow up. For Asians, Mean lowering LDL-C by 36.1% and/or to level 84.0 mg/dL with baseline mean LDL-C 134.2 mg/dL could significantly reduce the volume of CAP at follow up (SMD −0.211 mm3, 95% CI −0.331 ~ −0.092, p = 0.001). LDL-C lowering by rosuvastatin (mean 14.1 mg daily) and atorvastatin (mean 18.9 mg daily) could significantly decrease the volumes of CAP at follow up.

Conclusions

There was a different effect of LDL-C lowering on CAP between Westerns and Asians. For regressing CAP, Asians need lower dosage of statins or lower intensity LDL-C lowering therapy than Westerns.

Keywords

Low-density lipoprotein-cholesterolCoronary atherosclerotic plaqueIntravascular ultrasoundCoronary artery diseaseWesternAsian

Background

Atherosclerotic plaque is the hallmark and cornerstone of atherosclerotic disease. Disruption of coronary atherosclerotic plaque (CAP) may lead to sudden cardiac death, acute myocardial infarction, or unstable angina [1]. Intravascular ultrasound (IVUS) is considered to be gold standard for measurement of atherosclerotic plaque [2].

The meta-analysis of twenty trials evaluated the effects of LDL-C lowering on CAP indicated that intensive LDL-C lowering with statins could slow atherosclerotic plaque progression and lead to plaque regression [3]. But the meta-analysis did not investigate the effects of LDL-C lowering on CAP in different race.

In this meta-analysis, we investigated the difference between Western and Asian in the effect of LDL-C lowering therapy on the progression of the CAP from the current trials on LDL-C lowering therapy retarding the progression of the CAP and identified the different targets of LDL-C that result in the regression of the CAP for Western and Asian.

Methods

Materials and methods of this meta-analysis were detailed in the paper by Gao et al. [3].

Search strategy and selection criteria

An electronic literature search was performed to identify all relevant studies published in PubMed, EMBASE, and Cochrane databases in the English language from Jan. 1, 2000 to Sep. 13, 2014, using the terms “atherosclerosis” and “cholesterol blood level”. Trials were included using the criteria as: 1) randomized controlled or prospective, blinded end-points trials, and its primary end point was CAP change detected by IVUS; 2) report of LDL-C levels at baseline and follow-up; 3) data on the volume of CAP at baseline and follow-up, and volume of CAP was calculated as vessel volume minus lumen volume; Exclusion criteria were: 1) only CAP area or volume index or percent atheroma volume were detected; 2) the levels of LDL-C at baseline or follow-up were not provided; and 3) target plaques were unstable.

Data extraction and quality assessment

Two investigators independently reviewed all potentially eligible studies and collected data on patient and study characteristics, and any disagreement was resolved by consensus. The primary end point of this study was the volume change of CAP detected by IVUS. Quality assessments of trials were evaluated with Jadad quality scale.

Data synthesis and analysis

Volume changes of CAP from baseline to follow-up were analyzed using standardized mean differences (SMD).

Volume changes of plaque in every arm were used for pooled analysis. The trials were firstly grouped into group Western and Asian according to the location of the trials. Then, according to the levels and the reducing percentage of LDL-C at follow-up, the arms were grouped to following groups: ≤70, >70 ≤ 100 HP, >70 ≤ 100 MP, >70 ≤ 100 LP, >100 mg/dL; and <0, ≥0 < 30, ≥30 < 40, ≥40 < 50, ≥50% respectively [3], to investigate the effect of different levels of LDL-C at follow up on CAPs. According to statins, the arms were grouped to: rosuvastatin, atorvastatin, pitavastatin, simvastatin, fluvastatin and pravastatin groups, to investigate the effect of different statins on CAPs. The volume of CAP at follow up was compared with that at baseline to evaluate effect of LDL-C levels on regression of CAP.

Heterogeneity across trials (arms) was assessed via a standard χ 2 test with significance being set at p < 0.10 and also assessed by means of I 2 statistic with significance being set at I 2  > 50%. Pooled analyses were calculated using fixed-effect models, whereas random-effect models were applied in case of significant heterogeneity across trials (arms). Sensitivity analyses (exclusion of one study at one time) were performed to determine the stability of the results. Publication bias was assessed using the Egger regression asymmetry test. Statistical analyses were performed using STATA software 12.0 (StataCorp, College Station, Texas).

All continuous variables were expressed as mean ± SD, and continuous variables were compared between the Western and Asian groups using Student’s t test (SigmaStat 3.5). A P value <0.05 was considered to be statistically significant.

Results

Eligible studies

The flow of selecting studies for the meta-analysis was shown in Figure 1. Briefly, of the initial 673 articles, one hundred and twenty-two of abstracts were reviewed, resulting in exclusion of 102 articles, and 20 articles were reviewed in full text, resulting in exclusion of 10 trials and inclusion of 18 additional trials cited in the 20 articles. Twenty two RCTs [425] and six blinded end-points trial [2631] were carefully evaluated, and eight trials [4, 8, 9, 18, 19, 21, 27, 31] were excluded because of specific the index of plaque or lack of some data. Sixteen RCT (ESTABLISH [11], REVERSAL [10], A-PLUS [5], ACTIVATE [6], ILLUSTRATE [7], JAPAN-ACS [20], REACH [14], SATURN [16], ARTMAP [17], ERASE [23], STRADIVARIUS [24], PERISCOPE [25], and trials by Yokoyama M [12], by Kawasaki M [13], by Hong MK [15], and Tani S [22]) and four blinded end-points trial (ASTEROID [26], COSMOS [29], trial by Jensen LO [28] and trial by Nasu K [30]) were finally analyzed.
Figure 1

Flow diagram of study-screening process.

The characteristics of the included trials were as same as in the study [3] and shown in Table 1. Briefly, among the 20 trials, 10 trials are completed in European, America and Australia [10, 57, 16, 2326, 28], 10 in Asia [20, 1115, 17, 22, 29, 30], and there were 15 trials assessing statins (statin vs. usual care in 6 trials [1114, 22, 30]; intensive statin vs. moderate statin treatment in 5 trials [10, 1517, 20]; follow up vs baseline in 3 trial [26, 28, 29], before acute coronary syndrome (ACS) vs after ACS in one trial [23]), 2 trials assessing enzyme acyl–coenzyme A: cholesterol acyltransferase (ACAT) inhibition [5, 6], one trial assessing cholesteryl ester transfer protein (CETP) inhibitor torcetrapib [7], one trial assessing a decreasing obesity drug: rimonabant [24], and one trial assessing glucose-lowering agents [25]. Overall, 5910 patients with coronary heart disease (CHD) underwent serial IVUS examination for evaluating regression of CAP. Follow-up periods ranged from 2 to 24 months. The levels of LDL-C of each arm at baseline and follow-up were shown in Table 2.Risk of bias of included studies, evaluated through Cochrane’s methods, showed an overall acceptable quality of selected trials (Figures 2 and 3).
Table 1

Features of participating trials

Authors and trial name

Trial type and location

Objective

Year

N T/C

Study population

LDL-C at follow up

LDL-C reducing percentage

Treatments

Follow up

Main Results or Conclusion

Okazaki S11; ESTABLISH

RCT: prospective, open-label, randomized, single center study. Japan

Effects of statins on changes in plaque by IVUS

2004

24/24

ACS

70/119

−44/-0.004

Ato 20 vs Diet

6

Plaque volume was sigificantly reduced in the Ato group compared with the control group.

Nissen SE10; REVERSAL

RCT: Double-blind, randomized active control multicenter trial; USA

Effects of statins (intensive or moderate) on changes in plaque by IVUS

2004

253/249

CAD

79/110

−46/-25

Ato 80 vs Pra40

18

Ato reduced progression of coronary plaque compared with Pra. Compared with baseline values, Ato had no change in atheroma burden, whereas patients treated with Pra showed progression of coronary plaque.

Tardif JC5; A-PLUS

RCT: international, multicenter, double-blind, placebo-controlled, randomized trial. Canada, USA

Effects of different dosage of avasimibe on changes in plaque by IVUS

2004

108/98/117/109

CAD

100/102/101/91

7.8/9.1/10.9/1.7

Ava50, 250, and 750 vs Placebo on the basis of LDL-C < 125

18

Avasimibe did not favorably alter coronary atherosclerosis as assessed by IVUS.

Jensen LO28

Open non placebo controlled serial investigation; blinded end-points. Denmark

To investigate the effect of lipid lowering by simvastatin on coronary atherosclerotic plaque volumes and lumen.

2004

40

CAD

85

−46.3

Sim 40

15

Lipid-lowering therapy with Sim is associated with a significant plaque regression in coronary arteries.

Yokoyama M12

RCT: randomized, single center. Japan

Effects of statins on changes in plaque by IVUS

2005

29/30

stabl angina

87/124

−35/-0.075

Ato 10 vs Diet

6

Treatment with Ato may reduce volumes of coronary plaques.

Kawasaki M13

RCT: randomization, open-label, single-center study. Japan

Effects of statins on changes in plaque by IVUS

2005

17/18/17

stable angina

95/102/149

−39/-32/-0.02

Ato 20, Pra 20 vs Diet

6

Treatment with Ato and Pra may not significantly reduce volumes of coronary plaques.

Tani S22

RCT: a prospective, single-center, randomized, open trial. Japan

Investigated the effects of pravastatin on the serum levels of MDA-LDL and coronary atherosclerosis.

2005

52/23

stable angina

104/120

−20/-2.4

Pra 10–20 vs con

6

Plaque volume was sigificantly reduced in the Pra group compared with the control group.

Nissen SE6; ACTIVATE

RCT: randomized, multicenter. USA

Effects of pactimibe on changes in plaque by IVUS

2006

206/202

CAD

91/86

−9.6/-14.9

Pac100 vs Placebo

18

Pac is not an effective strategy for limiting atherosclerosis and may promote atherogenesis.

Nissen SE26; ASTEROID

Prospective, open-label blinded end-points. USA, Germany, France, Canada

Effects of Statins with different levels of LDL-C on changes in plaque by IVUS

2006

349

CAD

61

−53.2

Ros 40

24

Therapy using Ros can result in significant regression of atherosclerosis.

Yamada T14; REACH

RCT: open-labeled, randomized, multicenter study. Japan

Evaluate the effect of marked reduction of LDL-C in patients with CHD on progression of atherosclerosis.

2007

26/32

stable angina

83/115

−43/0

Ato 5 vs Con

12

Ato treatment prevented the further progression of atherosclerosis by maintaining LDL-C below 100 mg/dl in patients with CHD.

Nissen SE7; ILLUSTRATE

RCT: prospective, randomized, multicenter, double-blind clinical trial. North America or Europe

Effects of CETP inhibitor on changes in plaque by IVUS

2007

446/464

CAD

87/70

6.6/-13.3

Ato10-80 vs Ato + Tor 60 on the basis of LDL-C ≤ 100 by Ato

24

The Tor was associated with a substantial increase in HDL-C and decrease in LDL –C, and there was no significant decrease in the progression of coronary atherosclerosis.

Nissen SE25; PERISCOPE

RCT: prospective, randomized, multicenter, double-blind clinical trial. USA

To compare the effects of pioglitazone, and glimepiride on the progression of coronary atherosclerosis in patients with type 2 diabete and CAD

2008

181/179

CAD,DM

96.1/95.6

1.8/2.2

Gli1-4 mg vs Pio 15-45 mg on bases of statins therapy

18

In patients with type 2 diabetes and CAD, treatment with Pio resulted in a significantly lower rate of progression of coronary atherosclerosis compared with Gli.

Nissen SE24; STRADIVARIUS

RCT: Randomized, double-blinded, placebo -controlled, 2-group, parallel-group trial. North America, Europe, and Australia

The effect of rimonabant on regression of coronary disease in patients with the metabolic syndrome and CAD

2008

335/341

CAD,Obesity

87.6/86.3

−4.7/-3.6

Rim 20 mg vs Placebo on bases of statins therapy

18

Rim can reduce progression of coronary plaque, and increase HDL-C levels, decrease triglyceride levels.

Hiro T20; JAPAN-ACS

RCT: prospective, randomized, open-label, parallel group, multicenter. Japan

Effects of statins on changes in plaque by IVUS

2009

127/125

ACS

84/81

−36/-36

Ato 20 vs Pit 4

10

The administration of Pit or Ato in patients with ACS equivalently resulted in significant regression of coronary plaque volume.

Takayama T; COSMOS29

Prospective, open-label blinded end-points multicenter trial. Japan

Evaluate the effect of rosuvastatin on plaque volume in patients with stable CAD, including those receiving prior lipid-lowering therapy

2009

126

stable angina

83

−38.6

Ros <20

14

Ros exerted significant regression of coronary plaque volume in Japanese patients with stable CAD.

Rodés-Cabau; ERASE23

RCT: multicenter randomized placebo-controlled. Canada

Evaluate the early effects of newly initiated statin therapy on coronary atherosclerosis as evaluated by IVUS.

2009

38/36

ACS

77/63

8.5/-37

Before ACS vs After ACS

<2

Newly initiated statin therapy is associated with rapid regression of coronary atherosclerosis.

Nasu K30

Prospective and multicenter study with nonrandomized and non-blinded design, but blinded end. Japan

Evaluate the effect of treatment with statins on the progression of coronary atherosclerotic plaques of a nonculprit vessel by serial IVUS.

2009

40/39

stable angina

98.1/121

−32.3/-1.1

Flu 60 vs Con

12

One-year lipid-lowering therapy by Flu showed significant regression of plaque volume.

Hong MK15

RCT: randomized control trial. Korea.

Evaluated the effects of statin treatments for each component of coronary plaques.

2009

50/50

stable angina

78/64

−34.5/-44.8

Sim 20 vs Ros 10

12

Statin treatments might be associated with significant changes in necrotic core and fibrofatty plaque volume.

Nicholls SJ; SATURN16

RCT: a prospective, randomized, multicenter, double-blind clinical trial. USA

Compare the effect of these two intensive statin regimens on the progression of coronary atherosclerosis.

2011

519/520

CHD

70.2/62.6

−41.5/-47.8

Ato 80 vs Ros 40

24

Maximal doses of Ros and Ato resulted in significant regression of coronary atherosclerosis.

Lee CW17; ARTMAP

RCT: a prospective, single-center, open-label, randomized comparison trial. Korea.

Compared the effects of atorvastatin 20 mg/day versus rosuvastatin 10 mg/day on mild coronary atherosclerotic plaques.

2012

143/128

stable angina

56/53

−47/-49

Ato 20 vs Ros 10

6

Usual doses of Ato and Ros induced significant regression of coronary atherosclerosis in statin-naive patients.

Abbreviations: T Treatment, C Control, RCT randomized controlled trials, IVUS Intravascular ultrasound, CAD Coronary artery disease, ACS Acute coronary syndrome, CHD Coronary heart disease, Ato Atorvastatin, Ros Rosuvastatin, Pra Pravastatin, Pit Pitavastatin, Sim Simvastatin, Flu Fluvastatin, Con Control, Pac Pactimibe, Tor Torcetrapib, Ava 50, 250, 750, Avasimibe 50, 250, 750 mg, T/C Treat/Control, Gli Glimepiride, Pio Pioglitazone, Rim Rimonabant.

Table 2

The levels of LDL-C at baseline and follow up in each arm of included trials

Authors

Trial name

Management in each arm

N

LDL-C level

At baseline

At follow-up

Tardif JC

A-PLUS

Avasimibe50

108

92.8 ± 1.7

100*

Tardif JC

A-PLUS

Avasimibe250

98

93.4 ± 1.6

101.9*

Tardif JC

A-PLUS

Avasimibe750

117

91.4 ± 1.6

101.4*

Tardif JC

A-PLUS

Placebo

109

89.6 ± 1.6

91.1*

Okazaki S

ESTABLISH

Control

24

123.9 ± 35.3

119.4 ± 24.6

Okazaki S

ESTABLISH

Atorvastatin

24

124.6 ± 34.5

70.0 ± 25.0

Yokoyama M

 

Control

30

131.5 ± 23#

124.5 ± 24.1#

Yokoyama M

 

Atorvastatin

29

133 ± 13

87 ± 29

Nissen SE

REVERSAL

Atorvastatin

253

150.2 ± 27.9

78.9 ± 30.2

Nissen SE

REVERSAL

Pravastatin

249

150.2 ± 25.9

110.4 ± 25.8

Nissen SE

ACTIVATE

Pactimibe

206

101.4 ± 27.7

91.3

Nissen SE

ACTIVATE

Placebo

202

101.5 ± 31.1

86.4

Nissen SE

ILLUSTRATE

Atorvastatin

446

84.3 ± 18.9

87.2 ± 22.6

Nissen SE

ILLUSTRATE

Atorva + torcetrapib

464

83.1 ± 19.7

70.1 ± 25.4

Kawasaki M

 

Control

17

152 ± 20

149 ± 24

Kawasaki M

 

Pravastatin

18

149 ± 19

102 ± 13

Kawasaki M

 

Atorvastatin

17

155 ± 22

95 ± 15

Hiro T

JAPAN-ACS

Pitavastatin

125

130.9 ± 33.3

81.1 ± 23.4

Hiro T

JAPAN-ACS

Atorvastatin

127

133.8 ± 31.4

84.1 ± 27.4

Nissen SE

ASTEROID

Rosuvastatin

349

130.4 ± 34.3

60.8 ± 20.0

Takayama T

COSMOS

Rosuvastatin

126

140.2 ± 31.5

82.9 ± 18.7

Lee CW

ARTMAP

Atorvastatin

143

110 ± 31

56 ± 18

Lee CW

ARTMAP

Rosuvastatin

128

109 ± 31

53 ± 18

Yamada T

REACH

Atorvastatin

26

123 ± 17

83 ± 22

Yamada T

REACH

Control

32

115 ± 14

115 ± 30

Nasu K

 

Fluvastatin

40

144.9 ± 31.5

98.1 ± 12.7

Nasu K

 

Control

39

122.3 ± 18.9

121.0 ± 21.2

Nicholls SJ

SATURN

Atorvastatin

519

119.9 ± 28.9

70.2 ± 1.0

Nicholls SJ

SATURN

Rosuvastatin

520

120.0 ± 27.3

62.6 ± 1.0

Hong MK

 

Simvastatin

50

119 ± 30

78 ± 20

Hong MK

 

Rosuvastatin

50

116 ± 28

64 ± 21

Tani S

 

Pravastatin

52

130 ± 38

104 ± 20

Tani S

 

Control

23

123 ± 28

120 ± 30

Rodés-C Bef

ERASE

Statins before ACS

38

71 ± 23

77 ± 25

Rodés-C Aft

ERASE

Statins after ACS

36

100 ± 30

63 ± 17

Jensen LO

 

Simvastatin

40

158.7 ± 30.6

85.1 ± 22.1

Nissen SE

PERISCOPE

Statins + Gli

181

94.4 ± 32.9

96.1 ± 30.4

Nissen SE

PERISCOPE

Statins + Pio

179

93.5 ± 30.7

95.6 ± 28.9

Nissen SE

STRADIVARIUS

Statins + Rim

335

91.9 ± 27.9

87.6 ± 30.5

Nissen SE

STRADIVARIUS

Statins + Con

341

89.5 ± 32.2

86.3 ± 30.3

Note: *calculated on the bases of baseline levels and change percentage at follow up5.

#calculated according to Figure 2 in the paper12.

Figure 2

Methodological quality summary of each included trial.

Figure 3

Methodological quality graph: each methodological quality item presented as percentages across all included studies.

The effect of the levels of LDL-C at follow-up on regression of coronary atherosclerotic plaque in Western and Asian

For Western, meta-analysis indicated that LDL-C lowering in group ≤70 mg/dL could lead to regression of CAP, but LDL-C lowering in group >70 ≤ 100 HP, >70 ≤ 100 MP, >70 ≤ 100 LP and >100 mg/dL could not (Figure 4, Table 3).
Figure 4

Meta- analysis of the effects of reduction levels of LDL-C at follow up on the regression of coronary atherosclerotic plaque in Western. Abbreviations: Ato, Atorvastatin; Ros, Rosuvastatin; Pra, Pravastatin; Pit, Pitavastatin; Sim, Simvastatin; Flu, Fluvastatin; Con, Control; Pac, Pactimibe; Tor, Torcetrapib, Ava 50, 250, 750, Avasimibe 50, 250, 750 mg; Bef, before ACS; Aft, after ACS; Gli, Glimepiride; Pio, Pioglitazone; Rim, Rimonabant.

Table 3

Results of meta-analysis in each group and mean CAP volume in each group at baseline and follow up in Western and Asian

Group

Included arms (case)

CAP volume at baseline (mm3)

CAP volume at follow up (mm3)

Pooled SMD (95% CI,p)

Heterogeneity test

Sensitivity analyses

Egger’s test

χ 2 test (p)

I 2

Lower SMD (95% CI)

Upper SMD (95% CI)

Western

<70 mg

3(905)

171.4 ± 32.7

160.6 ± 29.7

−0.156(−0.248 ~ −0.064, 0.001)

0.33(0.886)

0

−0.139 (−0.257 ~ −0.021) Without 2006 ASTEROID Ros

−0.175 (−0.317 ~ −0.034) Without 2011 SATURN Ros

0.789

>70 ≤ 100 HPmg

3(812)

151.9 ± 30.4

147.9 ± 31.9

−0.065(−0.136 ~ 0.032, 0.189)

0.71(0.699)

0

  

0.987

>70 ≤ 100 MPmg

5(1548)

195.8 ± 2.3

191.8 ± 4.7

−0.045(−0.115 ~ −0.026, 0.215)

1.59(0.811)

0

  

0.500

>70 ≤ 100 LPmg

6(1061)

201.2 ± 15.1

197.3 ± 15.0

−0.045(−0.130 ~ 0.040, 0.301)

1.14(0.950)

0

  

0.241

>100 mg

3(464)

197.6 ± 3.5

201.1 ± 1.9

0.034(−0.094 ~ 0.163, 0.601)

0.03(0.984)

0

   

>50%

1(349)

212.2 ± 81.3

197.5 ± 79.1

−0.183(−0.332 ~ −0.035, 0.016)

     

>40 ≤ 50%

4(1332)

148.8 ± 24.0

143.1 ± 25.6

−0.095(−0.171 ~ −0.019, 0.014)

1.64(0.651)

0

−0.065 (−0.163 ~ 0.032) Without 2011 SATURN Ros

−0.116 (−0.201 ~ −0.032) Without 2004 REVERSAL Ato

0.804

>30 ≤ 40%

1(36)

169.1 ± 77.3

161.5 ± 75.2

−0.099(−0.561 ~ 0.363, 0.675)

0.00(0.000)

0

   

>0 ≤ 30%

6(1797)

195.6 ± 2.1

192.9 ± 5.1

−0.032(−0.098 ~ 0.033, 0.335)

2.45(0.784)

0

   

<0%

8(1276)

201.2 ± 13.8

198.3 ± 13.8

−0.034(−0.111 ~ 0.044, 0.396)

1.55(0.981)

0

  

0.087

Asian

<70 mg

4(345)

192.2 ± 59.9

179.9 ± 53.0

−0.157(−0.307 ~ −0.008, 0.039)

0.24(0.955)

0

−0.126 (−0.314 ~ 0.063) Without 2012 ARTMAP Ros

−0.187 (−0.383 ~ 0.008) Without 2012 ARTMAP Ato

0.970

>70 ≤ 100 HPmg

8(540)

96.4 ± 99.3

87.5 ± 92.0

−0.211(−0.331 ~ −0.092, 0.001)

2.68(0.913)

0

−0.177 (−0.314 ~ −0.040) Without 2009 JAPAN-ACS Ato

−0.231(−0.368 ~ −0.094) Without 2009 COSMOS Ros

0.083

>100 mg

8(235)

133.0 ± 139.6

134.3 ± 143.8

−0.029(−0.210 ~ 0.152, 0.750)

2.14(0.952)

0

   

>40 ≤ 50%

4(345)

192.2 ± 56.9

179.9 ± 53.0

−0.157(−0.307 ~ −0.008, 0.039)

0.33(0.955)

0

−0.126 (−0.314 ~ 0.063) Without 2012 ARTMAP Ros

−0.187 (−0.383 ~ 0.008) Without 2012 ARTMAP Ato

0.970

>30 ≤ 40%

9(558)

98.6 ± 98.5

90.0 ± 91.6

−0.206(−0.324 ~ −0.088, 0.001)

2.91(0.840)

0

−0.172 (−0.306 ~ −0.038) Without 2009 JAPAN-ACS Ato

−0.223 (−0.357 ~ −0.089) Without 2009 COSMOS Ros

0.004

>0 ≤ 30%

7(217)

130.2 ± 144.9

131.8 ± 149.4

−0.028(−0.216 ~ 0.161, 0.773)

2.14(0.907)

0

   

In group ≤70 mg/dL (including three arms) with mean 23.1 months of follow up, the volumes of CAP (160.6 mm3) at follow up were significantly decreased, compared with the volumes (171.4 mm3) at baseline [SMD −0.156 mm3, 95% CI (confidence interval) -0.248 ~ −0.064, p = 0.001]. There was no significant heterogeneity among arms (χ 2 for heterogeneity = 0.33, p =0.886, I2 = 0%).

Sensitivity analyses suggested that LDL-C lowering in group ≤70 mg/dL could lead to regression of CAP with reduction of the CAP volume ranged from −0.139 mm3 (SMD, 95% CI: −0.257 ~ −0.021) when the arm of 2006 ASTEROID Ros was omitted to −0.175 mm3 (SMD, 95% CI: −0.317 ~ −0.034) when the arm of 2011 SATURN Ros was omitted. No publication bias was found, the values of p by Egger’s test was 0.789.

For Asian, according to the levels of LDL-C at follow-up, the arms were grouped to three groups: ≤70, >70 ≤ 100 HP and >100 mg/dL.

LDL-C lowering in group ≤70 mg/dL and >70 ≤ 100 HP could lead to regression of CAP, but LDL-C lowering in group >100 mg/dL could not (Figure 5, Table 3).
Figure 5

Meta- analysis of the effects of reduction levels of LDL-C at follow up on the regression of coronary atherosclerotic plaque in Asian. Abbreviation as in Figure 4.

In group ≤70 mg/dL (including four arms) with mean 6.9 months of follow up and group >70 ≤ 100HP mg/dL (including eight arms) with mean 11.0 months of follow up, the volumes of CAP (179.9, 87.5 mm3 respectively) at follow up were significantly decreased, compared with the volumes (192.2, 96.4 mm3 respectively) at baseline [SMD −0.157 mm3, 95% CI −0.307 ~ −0.008, p = 0.039; SMD −0.211 mm3, 95% CI −0.331 ~ −0.092, p = 0.001; respectively]. There was no significant heterogeneity among arms (χ 2 for heterogeneity = 0.24, p =0.955, I2 = 0% for group ≤70 mg/dL; χ 2 for heterogeneity = 2.68, p =0.913, I2 = 0% for group >70 ≤ 100HP mg/dL).

Sensitivity analyses suggested that LDL-C lowering in group >70 ≤ 100 HP mg/dL could lead to regression of CAP with reduction of the CAP volume ranged from −0.177 mm3 (SMD, 95% CI: −0.314 ~ −0.040) when the arm of 2009 JAPAN-ACS Ato was omitted to −0.231 mm3 (SMD, 95% CI: −0.368 ~ −0.094) when the arm of 2009 COSMOS Ros was omitted; but that LDL-C lowering in group ≤ 70 mg/dL could not significantly lead to regression of CAP with reduction of the CAP volume when the arm of 2012 ARTMAP Ros or 2012 ARTMAP Ato was omitted (Table 3).

No publication bias was found, the values of p by Egger’s test for group ≤70 and >70 ≤ 100HP mg/dL were 0.970, 0.083 respectively.

The effect of the LDL-C reducing percentage at follow-up on regression of CAP in Western and Asian

For Western, meta-analysis showed that LDL-C lowering in group ≥40 < 50, ≥50% could lead to regression of CAP, but LDL-C lowering in group <0, ≥0 < 30% and ≥30 < 40 could not (Figure 6, Table 3).
Figure 6

Meta- analysis of the effects of reduction percentages of LDL-C at follow up on the regression of coronary atherosclerotic plaque in Western. Abbreviation as in Figure 4.

In group ≥40 < 50% (including four arms) with mean 22.6 months of follow up, the volumes of CAP (143.1 mm3) at follow up were significantly decreased, compared with the volumes (148.8 mm3) at baseline (SMD −0.095 mm3, 95% CI −0.171 ~ −0.019, p = 0.014). There was no significant heterogeneity among arms (χ 2 for heterogeneity = 1.64, P = 0.651, I2 = 0%).

Sensitivity analyses showed that LDL-C lowering in group ≥40 < 50 could still lead to regression of CAP with reduction of the plaque volume ranged from −0.065 mm3 (95% CI −0.163 ~ 0.032) when the arm of 2011 SATURN Ros was omitted to −0.116 mm3 (SMD, 95% CI −0.201 ~ −0.032) when 2004 REVERSAL Ato was omitted. Publication bias analysis suggested the values of p by Egger’s test were 0.804.

In group group <0, ≥0 < 30% and ≥30 < 40, meta-analysis were showed in Table 3.

For Asian, according to the reducing percentage of LDL-C at follow-up, the arms were grouped to following groups: ≥0 < 30, ≥30 < 40, ≥40 < 50.

LDL-C lowering in group ≥30 < 40, ≥40 < 50% could lead to regression of CAP, but LDL-C lowering in group ≥0 < 30% could not (Figure 7, Table 3).
Figure 7

Meta- analysis of the effects of reduction percentages of LDL-C at follow up on the regression of coronary atherosclerotic plaque in Asian. Abbreviation as in Figure 4.

In group ≥30 < 40% (including nine arms) with mean 10.9 months of follow up, and group ≥40 < 50% (including four arms) with mean 6.9 months of follow up, the volumes of CAP (90.0, 179.9 mm3 respectively) at follow up were significantly decreased, compared with the volumes (98.6, 192.2 mm3 respectively) at baseline (SMD −0.206 mm3, 95% CI −0.324 ~ −0.088, p = 0.001; SMD −0.157 mm3, 95% CI −0.307 ~ −0.008, p = 0.039; respectively). There was no significant heterogeneity among arms (χ 2 for heterogeneity = 2.91, P = 0.840, I2 = 0%; χ 2 for heterogeneity = 0.33, p =0.955, I2 = 0%; for group ≥30 < 40, and group ≥40 < 50 respectively).

Sensitivity analyses showed that LDL-C lowering in group ≥30 < 40% could still lead to regression of CAP with reduction of the plaque volume ranged from −0.172 mm3 (95% CI −0.306 ~ −0.038) when the arm of 2009 JAPAN-ACS Ato was omitted to −0.223 mm3 (SMD, 95% CI −0.357 ~ −0.089) when 2009 COSMOS Ros was omitted. Publication bias analysis suggested that bias was significant with 0.004 of p value by Egger’s test.

Mean levels of LDL-C at baseline and follow up, mean reducing percentage of LDL-C in each group were showed in Table 4.
Table 4

Levels and reducing percentage of LDL-C and duration in each group in Western and Asian (Mean ± SD)

Group

N

Mean LDL-C at baseline (mg)

Mean LDL-C at follow up (mg)

Mean reducing percentage

Actual range of reducing percentage

Duration (month)

Western

≤70 mg

905

123.2 ± 6.9

61.9 ± 0.9

49.4 ± 3.5

37 ~ 53

23.1 ± 4.3

>70 ≤ 100 HPmg

812

131.3 ± 15.2

73.6 ± 4.8

43.2 ± 2.2

41.5 ~ 46.7

21.7 ± 3.1

>70 ≤ 100 MPmg

1548

91.3 ± 6.9

82.4 ± 8.2

9.0 ± 4.5

3.6 ~ 14.9

19.8 ± 2.7

>70 ≤ 100 LPmg

1061

88.5 ± 5.5

91.5 ± 5.4

−4.7 ± 2.5

−1.7 ~ −8.5

19.9 ± 4.5

>100 mg

464

123.4 ± 28.9

106.3 ± 4.4

8.7 ± 17.5

−10.9 ~ 25.0

18.0 ± 0.0

>50%

349

130.4 ± 0.0

60.8 ± 0.0

53.4 ± 0.0

53.4 ~ 53.4

24.0 ± 0.0

>40 ≤ 50%

1332

126.9 ± 13.1

69.3 ± 6.5

45.0 ± 2.8

41.5 ~ 47.8

22.6 ± 2.7

>30 ≤ 40%

36

100.2 ± 30.2

63.1 ± 17.4

37.0

37 ~ 37

2.0 ± 0.0

>0 ≤ 30%

1797

99.4 ± 21.4

86.2 ± 12.2

11.2 ± 6.9

3.6 ~ 25.0

19.5 ± 2.6

<0%

1276

89.1 ± 5.3

93.2 ± 6.2

−5.6 ± 3.1

−1.7 ~ −10.9

19.6 ± 4.2

Asian

≤70 mg

345

111.5 ± 4.3

57.0 ± 5.0

47.2 ± 1.7

44 ~ 49

6.9 ± 2.1

>70 ≤ 100 HPmg

540

134.2 ± 7.8

84.0 ± 5.0

36.1 ± 1.8

32.3 ~ 39.0

11.0 ± 2.2

>100 mg

235

128.6 ± 10.5

117.2 ± 11.9

7.3 ± 10.7

0 ~ 32

7.8 ± 2.8

>40 ≤ 50%

345

111.5 ± 4.3

57.0 ± 5.0

47.2 ± 1.7

44 ~ 49

6.9 ± 2.1

>30 ≤ 40%

558

134.7 ± 8.1

84.6 ± 5.8

36.0 ± 1.9

32 ~ 39

10.9 ± 2.4

>0 ≤ 30%

217

126.9 ± 9.1

118.3 ± 11.5

5.3 ± 8.3

0 ~ 20.0

8.0 ± 2.8

The effect of lowering LDL-C by statins on regression of coronary atherosclerotic plaque in Western and Asian

For Western, atorvastatin, rosuvastatin, pravastatin and simvastatin were used in trials to investigate the effects of LDL-C lowering on CAP. Meta-analysis indicated that LDL-C lowering by rosuvastatin could lead to regression of CAP, but LDL-C lowering by atorvastatin, pravastatin, and simvastatin could not (Figure 8, Table 5).
Figure 8

Meta- analysis of the effects of LDL-C lowering by different statins on the regression of coronary atherosclerotic plaque in Western. Abbreviation as in Figure 4.

Table 5

Results of meta-analysis in different statins groups in Western and Asian

Group

Included arms (and case)

Pooled SMD (95% CI,p)

Heterogeneity test

Sensitivity analyses

Egger’s test

χ 2 test (p)

I 2

Lower SMD (95% CI)

Upper SMD (95% CI)

Western

Rosuvastatin

2(869)

−0.158(−0.253 ~ −0.064, 0.001)

0.18(0.672)

0

−0.142 (−0.263 ~ −0.020) Without 2006 ASTEROID Ros

−0.183 (−0.332 ~ −0.035) Without 2011 SATURN Ros

0.000

Atorvastatin

2(772)

−0.062(−0.162 ~ 0.038, 0.225)

0.62(0.432)

0

  

0.000

Pravastatin

1(249)

0.045(−0.131 ~ 0.221, 0.616)

     

Simvastatin

1(40)

−0.133(−0.572 ~ 0.306, 0.552)

     

Asian

Rosuvastatin

3(304)

−0.172(−0.331 ~ −0.012, 0.035)

0.17(0.917)

0

−0.143 (−0.352 ~ 0.066) Without 2012 ARTMAP Ros

−0.189 (−0.397 ~ 0.019) Without 2009 COSMOS Ros

0.660

Atorvastatin

6(366)

−0.185(−0.330 ~ −0.040, 0.013)

1.94(0.858)

0

−0.113 (−0.292 ~ 0.068) Without 2009 JAPAN-ACS Ato

−0.230 (−0.417 ~ −0.044) Without 2012 ARTMAP Ato

0.456

Pravastatin

2(70)

−0.197(−0.529 ~ 0.135, 0.245)

0.26(0.608)

0

   

Pitavastatin

1(125)

−0.304(−0.553 ~ −0.055, 0.017)

     

Fluvastatin

1(40)

−0.169(−0.608 ~ 0.270, 0.450)

     

Simvastatin

1(50)

−0.074(−0.467 ~ 0.318, 0.710)

     

LDL-C lowering by rosuvastatin (mean 40.0 mg daily for mean 24 months) could significantly decrease the volumes of CAP at follow up, compared with the volumes at baseline (SMD −0.158 mm3, 95% CI: −0.253 ~ −0.064, p = 0.001). There was no significant heterogeneity among arms (χ 2 for heterogeneity = 0.18, p =0.672, I2 = 0%).

Sensitivity analyses suggested that lowering LDL-C by rosuvastatin could lead to regression of CAP with reduction of the plaque volume ranged from −0.142 mm3 (SMD, 95% CI: −0.263 ~ −0.020) when the arm of 2006 ASTEROID Ros was omitted to −0.183 mm3 (SMD, 95% CI: −0.332 ~ −0.035) when the arm of 2011 SATURN Ros was omitted. But publication bias was found, the values of p by Egger’s test was 0.000 (Table 5).

For Asian, atorvastatin, rosuvastatin, pitavastatin, pravastatin, fluvastatin and simvastatin were used in trials to investigate the effects of LDL-C lowering on CAP. Meta-analysis indicated that LDL-C lowering by rosuvastatin, atorvastatin could lead to regression of CAP, but LDL-C lowering by pitavastatin, pravastatin, fluvastatin and simvastatin could not (Figure 9, Table 5).
Figure 9

Meta- analysis of the effects of LDL-C lowering by different statins on the regression of coronary atherosclerotic plaque in Asian. Abbreviation as in Figure 4.

LDL-C lowering by rosuvastatin (mean 14.1 mg daily for mean 10.3 months), atorvastatin (mean 18.9 mg daily for mean 7.8 months) could significantly decrease the volumes of CAP at follow up, compared with the volumes at baseline (SMD −0.172 mm3, 95% CI: −0.331 ~ −0.012, p = 0.035; SMD −0.185, 95% CI: −0.330 ~ −0.040, p = 0.013; respectively). There was no significant heterogeneity among arms (χ 2 for heterogeneity = 0.17, p =0.917, I2 = 0% for rosuvastatin; χ 2 for heterogeneity = 1.94, p =0.858, I2 = 0% for atorvastatin).

Sensitivity analyses suggested that lowering LDL-C by rosuvastatin could not significantly lead to regression of CAP when the arm of 2012 ARTMAP Ros or 2009 COSMOS Ros was omitted. Also, Lowering LDL-C by atorvastatin could not significantly lead to regression of CAP when the arm of 2009 JAPAN-ACS Ato was omitted. No publication bias was found, the values of p by Egger’s test for rosuvastatin and atorvastatin group were 0.660, 0.456 respectively (Table 5).

Intensity of lowering LDL-C by different statins was shown in Table 6. Rosuvastatin and atorvastatin could reduce LDL-C by more than 40%.
Table 6

Levels and reducing percentage of LDL-C, dosage and duration in different statin group in Western and Asian (Mean ± SD)

Group

N

Age

MeanLDL-C at baseline (mg)

MeanLDL-C at follow up (mg)

Mean reducing percentage

Statin dosage (mg)

Duration (month)

Western

Rosuvastatin

869

57.8 ± 0.6

124.2 ± 5.1

61.9 ± 0.9

49.9 ± 2.6

40.0 ± 0.0

24.0 ± 0.0

Atorvastatin

772

57.2 ± 1.0

129.8 ± 14.2

73.1 ± 4.1

43.0 ± 2.1

80.0 ± 0.0

22.0 ± 2.8

Pravastatin

249

56.6 ± 0.0

150.2 ± 0.0

110.4 ± 0.0

25.0 ± 0.0

40.0 ± 0.0

18.0 ± 0.0

Simvastatin

40

57.7 ± 0.0

158.7 ± 0.0

85.1 ± 0.0

46.7 ± 0.0

40.0 ± 0.0

25.0 ± 0.0

Asian

Rosuvastatin

304

58.9 ± 3.3

123.1 ± 14.6

67.2 ± 13.8

44.0 ± 4.8

14.1 ± 4.9

10.3 ± 3.7

Atorvastatin

366

60.9 ± 3.0

124.1 ± 12.7

72.9 ± 14.2

40.7 ± 5.5

18.9 ± 2.9

7.8 ± 2.2

Pitavastatin

125

62.5 ± 11.5

130.9 ± 33.3

81.1 ± 23.4

36.2 ± 19.5

4

8 ~ 12

Pravastatin

70

64.0 ± 1.8

134.9 ± 8.4

130.5 ± 0.9

23.1 ± 5.3

16.3 ± 2.2

6.0 ± 0.0

Fluvastatin

40

63.0 ± 10.0

144.9 ± 31.5

98.1 ± 12.7

32.3

60

12

Simvastatin

50

58.0 ± 0.0

119.0 ± 0.0

78.0 ± 0.0

34.5 ± 0.0

20.0 ± 0.0

12.0 ± 0.0

The difference between Western and Asian in usage of statins

The meta analysis showed that rosuvastatin and atorvastatin can regress CAP (Table 5). LDL-C levels, intensity of lowering LDL-C by rosuvastatin and atorvastatin, its dosage and duration were compared between Western and Asian (Table 7). Intensity of lowering LDL-C by rosuvastatin and atorvastatin in Western group were similar to that in Asian group, but the dosages of rosuvastatin and atorvastatin in Asian group were significantly lower than those in Western group, and the duration of statins administration in Asian group were significantly shorter than those in Western, as showed in Table 7.
Table 7

Comparison between Western and Asian in rosuvastatin and atorvastatin

 

Rosuvastatin

Atorvastatin

 

Western

Asian

p

Western

Asian

p

N/arm

869/2

304/3

 

772/2

366/6

 

Mean LDL-C at baseline (mg)

124.2 ± 5.1

123.1 ± 14.6

0.928

129.8 ± 14.2

124.1 ± 12.7

0.610

Mean LDL-C at follow up (mg)

61.9 ± 0.9

67.2 ± 13.8

0.642

73.1 ± 4.1

72.9 ± 14.2

0.986

LDL-C Mean reducing percentage

49.9 ± 2.6

44.0 ± 4.8

0.221

43.0 ± 2.1

40.7 ± 5.5

0.600

Statin dosage (mg)

40.0 ± 0.0

14.1 ± 4.9

0.006

80.0 ± 0.0

18.9 ± 2.9

<0.001

Duration (month)

24.0 ± 0.0

10.3 ± 3.7

0.016

22.0 ± 2.8

7.8 ± 2.2

<0.001

Discussion

This meta-analysis revealed that intensive LDL-C lowering can regress CAP both in Western and Asian. For regressing CAP, the dosage of statins administrated in Westerns was different from that in Asians. Asians need lower dosage of atorvastatin or rosuvastatin than Westerns though there was no difference between Westerns and Asians in pharmacokinetic and pharmacodynamic study [32, 33].

The effect difference of LDL-C lowering on CAP between Western and Asian

For Western including American, Canadian, German, French, English, Australian and Dane [10, 57, 16, 2326, 28], the meta-analysis (Table 3) in subgroup ≤70 mg and ≥40 < 50% of Western indicated that LDL-C level lowering to <69.3 mg or reducing by > 45% for 22.6 months of follow up (Table 4) could lead to regression of CAP, but the meta-analysis (Table 3) in subgroup >70 ≤ 100 HP mg of Western showed that LDL-C level lowering to 73.2 mg or reducing by 43.6% for 21.7 months of follow up (Table 4) was not enough for regressing CAP.

For Asian including Japanese and Korean [20, 1115, 17, 22, 29, 30], the meta-analysis in subgroup ≤70 mg and ≥40 < 50% of Asian indicated that LDL-C level lowering to 57.0 mg or reducing by 47.2% for 6.9 months of follow up could lead to regression of CAP, but sensitivity analyses showed that LDL-C lowering in this two subgroup could not significantly lead to regression of CAP when the arm of 2012 ARTMAP Ros or 2012 ARTMAP Ato was omitted (Table 3). The meta-analysis in subgroup ≥ 30 < 40% of Asian indicated that LDL-C level lowering to 84.6 mg or reducing by 36.0% for 10.9 months of follow up could also lead to regression of CAP, but publication bias was significant. The meta-analysis in subgroup >70 ≤ 100HP mg of Asian with good sensitivity and no publication bias indicated that LDL-C level lowering to 84.0 mg or reducing by 36.1% for 11 months of follow up with could lead to regression of CAP (Table 3).

Taken all the results of meta-analysis together, for Western, it was recommended that LDL-C level might be reduced by >45% or to a target level < 69 mg/dL for regressing CAP; for Asian, LDL-C level might be reduced by >36% or to a target level < 84 mg/dL.

Different effects of statins on Westerns and Asians

Whether statins has different effect on Westerns and Asians remains to be settled.

The study by Lee E et al. [34] and MEGA Study [35] suggested statins have different effects on Westerns and Asians. In 2005, Lee E et al. [34] prospectively examined the pharmacokinetics of rosuvastatin in White and Asian individuals living in Singapore, and reported that plasma exposure to rosuvastatin and its metabolites was significantly higher in Chinese, Malay, and Asian-Indian subjects compared with Western subjects living in the same environment. But the mechanisms underlying ethnic differences in rosuvastatin disposition remain to be unearthed [36]. MEGA Study [35] indicated that a small dose of pravastatin that was half the dose administered to western patients, reduced LDL-C by 19-22% (which is lower than that reductions of 23–35% in western patients), but could substantially reduce the risk of coronary heart disease in Japanese.

But two meta-analysis did not demonstrate the difference of rosuvastatin and atorvastatin on Westerns and Asians. The meta-analysis including the 36 trials of pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients did not confirm that there was significant difference in the exposure-response relationship for LDL-C reduction between Westerners and Asians [33].The meta-analysis including 22 pharmacokinetic studies also demonstrated no differences in the systemic exposure to atorvastatin between Asian and Caucasian subjects [32].

Our meta-analysis revealed that there were difference of rosuvastatin and atorvastatin in lowering LDL-C and regressing CAP between Westerns and Asians. The meta-analysis of rosuvastatin including 2 trials with 869 Western patients indicated that 40 mg of rosuvastatin daily for 24 months with reducing LDL-C by 49.9% could regress CAP. But the meta-analysis of rosuvastatin including 3 trials with 304 Asian patients showed that 14.1 mg of rosuvastatin daily for 10.3 months with reducing LDL-C by 44.0% could also regress CAP though the result of sensitivity analyses is not as good as that in Western (Table 5). The meta-analysis of atorvastatin including 2 trials with 772 Western patients showed that 80 mg of atorvastatin daily for 22 months with reducing LDL-C by 43.0% could not significantly regress CAP. But the meta-analysis of atorvastatin including 6 trials with 366 Asian patients demonstrated that 18.9 mg of atorvastatin daily for 7.8 months with reducing LDL-C by 40.7% could significantly regress CAP though the result of sensitivity analyses is not as good as that expected (Table 5).

Comparison between Western and Asian in using rosuvastatin and atorvastatin indicated that the dosages of rosuvastatin and atorvastatin in Asian group were significantly lower than those in Western (Table 7).

Based on this meta-analysis, reducing LDL-C by >40% in Westerns need atorvastatin 80 mg or rosuvastatin 40 mg, but in Asians need only atorvastatin 18.9 mg or rosuvastatin 14.1 mg. For regressing CAP, 40 mg of rosuvastatin might be daily administrated in Western for 24 months; 14.1 mg of rosuvastatin or 18.9 mg of atorvastatin might be daily administrated in Asian for 10.7 or 7.8 months respectively.

Study limitation

As with the meta-analysis [3], this study has some limitations. There might be publication bias, difference of the method detected and follow up duration. But those differences in measurements and plaque selection did not affect the change of the target plaque with LDL-C levels. So, it has little effect on homogeneous of studies, and on the relationship between CAP change and LDL-C level. But the trials of single statin on LDL-C and CAP of specific population (for example, 2 trials about atorvastatin on Western with 727 participants or 6 on Asian with 366 in Table 5) were limited, the effect of statin on specific population remains to be investigated. The duration of follow up between Western and Asian was different (Table 4, 6 and 7), and treatment duration might have some effect on CAP regression. But the trials from Asian and Western were respectively meta-analysed in this study. Therefore, the difference in follow-up duration between Asian and Western did not influence the results of the meta-analysis. The CAP regression in short period of statins therapy in Asian suggested that the CAPs in Asian were easily regressed by statins.

This meta-analysis did not investigate the effect of reduction of LDL-C on adverse cardiovascular events because all participants of the included trial must be alive at follow up. But in the Extended-ESTABLISH study, the incidence of adverse cardiovascular events in statin group with CAP regression were reduced to half that seen in the control group [37]. In the Extended JAPAN-ACS study [38], there was no significantly different association of incidence of adverse cardiovascular events with the CAP regression extent, but that greater external elastic membrane volume regression (<−6.56%) had a significantly lower incidence of cumulative events than the lesser suggested the importance of CAP regression in reducing adverse cardiovascular events. A meta-analysis [39] included 7864 CAD patients showed that rates of plaque volume regression were significantly associated with the incidence of MI or revascularization.

Conclusions

LDL-C lowering therapy has a different effect on atherosclerotic plaque between Westerns and Asians. This systemic review demonstrated that there is a different effect of LDL-C lowering on CAP between Westerns and Asians. For regressing CAP, Asians need lower dosage of statins or lower intensity LDL-C lowering therapy (by >36%) than Westerns (by 45%).

Abbreviations

ACAT: 

Acyl–coenzyme A: cholesterol acyltransferase

ACS: 

Acute coronary syndrome

ATP III: 

Adult Treatment Panel III

CAD: 

Coronary artery disease

CAG: 

Coronary angiography

CAP: 

Coronary atherosclerotic plaque

CETP: 

Cholesteryl ester transfer protein

CHD: 

Coronary heart disease

IVUS: 

Intravascular ultrasound

CI: 

Confidence interval

LDL-C: 

Low-density lipoprotein cholesterol

RCT: 

Randomized controlled trial

SMD: 

Standardized mean differences.

Declarations

Authors’ Affiliations

(1)
The Department of Cardiology, Chinese PLA General Hospital
(2)
The First Department of Geriatric Cardiology, Chinese PLA General Hospital
(3)
The First Clinics, Administrative and Supportive Bureau, Chinese PLA General Logistics Department

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