Background
Methods
Search strategy and selection criteria
Data extraction and quality assessment
Data synthesis and analysis
Results
Eligible studies
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 S [14];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 SE [13]; 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 JC [21]; 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 LO [39] | 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 M [15] | RCT: randomized, single center. Japan | Effects of statins on changes in plaque by IVUS | 2005 | 29/30 | Stable angina | 87/124 | -35/-0.075 | Ato 10 vs Diet | 6 | Treatment with Ato may reduce volumes of coronary plaques. |
Kawasaki M [16] | 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 S [33] | 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 SE [22]; 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 SE [37]; 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 T [26]; 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 SE [23]; 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 SE [36]; 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 SE [35]; 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 T [12]; 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; COSMOS [40] | 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; ERASE [34] | 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 K [41] | 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 MK [27] | 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; SATURN [28] | 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 CW [29]; 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. |
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 |
The effect of the levels of LDL-C at follow-up on regression of coronary atherosclerotic plaque
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) | ||||||
≤70 mg | 7 (1250) | 177.1±41.9 | 125.9±38.6 | -0.156 (-0.235~ -0.078, 0.000) | 0.57 (0.997) | 0 | -0.146 (-0.238~ -0.054) | -0.167 (-0.270~ -0.064) | 0.835 |
Without 2006 ASTEROID Ros | Without 2011 SATURN Ros | ||||||||
>70≤100HP mg | 11 (1352) | 129.7±72.3 | 123.8±69.8 | -0.123 (-0.199~ -0.048, 0.001) | 6.83 (0.741) | 0 | -0.103 (-0.182~ -0.024) | -0.151 (-0.235~ -0.067) | 0.501 |
Without 2009 JAPAN-ACS Ato | Without 2004 REVERSAL Ato | ||||||||
>70≤100MP mg | 5 (1548) | 195.8±2.3 | 191.8±4.7 | -0.045 (-0.115~ -0.026, 0.215) | 1.59 (0.811) | 0 | -0.016 (-0.103~ -0.066) | -0.061 (-0.140~ -0.019) | 0.500 |
Without 2007 ILLUSTRATE Ato+Tor | Without 2008 STRADIVARIUS Con | ||||||||
>70≤100LP mg | 6 (1061) | 201.2±15.1 | 197.3±15.0 | -0.045 (-0.130~0.040, 0.301) | 1.14 (0.950) | 0 | -0.024 (-0.136~ 0.087) | -0.059 (-0.148~ 0.031) | 0.241 |
Without 2007 ILLUSTRATE Ato | Without 2004 A-PLUS Ava 50 | ||||||||
>100 mg | 10 (669) | 175.9±86.4 | 178.7±89.1 | 0.017 (-0.090~0.124, 0.757) | 2.37 (0.984) | 0 | -0.000 (-0.135~ 0.136) | 0.039 (-0.073~ 0.151) | 0.692 |
Without 2004 REVERSAL Pro | Without 2005 Tani S Pra | ||||||||
<0% | 8 (1276) | 201.2±13.8 | 198.3±13.8 | -0.034 (-0.111~ 0.044, 0.396) | 1.55 (0.981) | 0 | -0.012 (-0.109~ 0.084) | -0.044 (-0.125~ 0.037) | 0.087 |
Without 2007 ILLUSTRATE Ato | Without 2004 A-PLUS Ava 50 | ||||||||
>0≤30% | 13 (2014) | 188.6±51.7 | 186.3±52.7 | -0.032 (-0.093~ 0.030, 0.315) | 4.59 (0.970) | 0 | -0.010 (-0.080~ 0.061) | -0.042 (-0.108~ 0.024) | 0.537 |
Without 2007 ILLUSTRATE Ato+Tor | Without 2004 REVERSAL Pra | ||||||||
>30≤40% | 10 (594) | 102.9±96.9 | 94.3±90.4 | -0.199 (-0.314~ -0.085, 0.001) | 3.10 (0.960) | 0 | -0.166 (-0.295~ -0.038) | -0.214 (-0.342~ -0.085) | 0.024 |
Without 2009 JAPAN-ACS Ato | Without 2009 COSMOS Ros | ||||||||
>40≤50% | 8 (1677) | 157.8±37.8 | 150.7±36.3 | -0.108 (-0.176~ -0.040, 0.002) | 2.50 (0.927) | 0 | -0.093 (-0.174~ -0.011) | -0.126 (-0.200~ -0.053) | 0.605 |
Without 2011 SATURN Ros | Without 2004 REVERSAL Ato | ||||||||
>50% | 1 (349) | 212.2±81.3 | 197.5±79.1 | -0.183 (-0.332~ -0.035, 0.016) |
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) |
---|---|---|---|---|---|---|
≤70 mg | 1250 | 120.0±8.2 | 60.6±3.5 | 48.8±3.3 | 37~53.2 | 18.6±8.2 |
>70≤100HP mg | 1352 | 132.4±12.9 | 77.8±7.0 | 40.4±4.0 | 32.3~46.7 | 17.4±5.9 |
>70≤100MP mg | 1548 | 91.3±6.9 | 82.4±8.2 | 9.1±4.5 | 3.6~14.9 | 19.8±2.7 |
>70≤100LP mg | 1061 | 88.5±5.5 | 91.5±5.4 | -4.7±2.5 | -1.7~-8.5 | 19.9±4.5 |
>100 mg | 699 | 125.1±24.4 | 110.0±9.3 | 8.3±15.6 | -10.9~32 | 14.6±5.1 |
<0% | 1276 | 89.1±5.3 | 93.2±6.2 | -5.6±3.1 | -1.7~-10.9 | 19.6±4.2 |
>0≤30% | 2014 | 102.4±22.1 | 89.7±15.7 | 10.6±7.3 | 0~25 | 18.3±4.5 |
>30≤40% | 594 | 132.6±11.4 | 83.3±7.7 | 36.1±1.9 | 32~39 | 10.3±3.1 |
>40≤50% | 1677 | 123.7±13.4 | 66.8±8.0 | 45.4±2.8 | 41.5~49 | 19.4±6.9 |
>50% | 349 | 130.4±34.3 | 60.8±20.0 | 53.2 | 53.2 | 24 |
The effect of the LDL-C reducing percentage at follow-up on regression of CAP
The effect of lowering LDL-C by statins on regression of coronary atherosclerotic plaque
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) | ||||
Rosuvastatin | 5 (1173) | -0.162 (-0.234~ -0.081, 0.000) | 0.37 (0.985) | 0 | -0.153 (-0.249~-0.056) | -0.178 (-0.287~-0.069) | 0.770 |
Without 2006 ASTEROID Ros | Without 2011 SATURN Ros | ||||||
Atorvastatin | 8 (1138) | -0.101 (-0.184~ -0.019, 0.016) | 4.44 (0.728) | 0 | -0.075 (-0.162~0.012) | -0.132 (-0.225~-0.038) | 0.582 |
Without 2009 JAPAN-ACS Ato | Without 2004 REVERSAL Ato | ||||||
Pitavastatin | 1 (125) | -0.304 (-0.553~-0.055, 0.017) | |||||
Fluvastatin | 1 (40) | -0.169 (-0.608~0.270, 0.450) | |||||
Simvastatin | 2 (90) | -0.10 (-0.393~ 0.192, 0.501) | 0.04 (0.846) | 0 | -0.074 (-0.467~0.318) | -0.133 (-0.572~0.360) | 0.000 |
Without 2004 Jensen LO Sim | Without 2009 Hong MK Sim | ||||||
Pravastatin | 3 (319) | -0.008 (-0.163~0.147, 0.920) | 1.86 (0.395) | 0 | -0.005 (-0.165~0.154) | 0.039 (-0.131~0.208) | 0.528 |
Without 2005 Kawasaki M Pra | Without 2005 Tani S Pra |
Group | N | Age | MeanLDL-C at Baseline (mg) | MeanLDL-C at Follow up (mg) | Mean Reducing percentage | Statin dosage (mg) | Duration (month) |
---|---|---|---|---|---|---|---|
Rosuvastatin | 1173 | 58.1±1.8 | 123.9±8.6 | 63.3±7.4 | 48.4±4.2 | 33.3±11.6 | 20.5±6.3 |
Atorvastatin | 1138 | 58.4±2.5 | 128.0±14.0 | 73.0±8.7 | 42.3±3.7 | 60.3±28.6 | 17.5±7.1 |
Pitavastatin | 125 | 62.5±11.5 | 130.9±33.3 | 81.1±23.4 | 36.2±19.5 | 4 | 8~12 |
Fluvastatin | 40 | 63.0±10.0 | 144.9±31.5 | 98.1±12.7 | 32.3 | 60 | 12 |
Simvastatin | 90 | 57.9±0.1 | 136.61±5.3 | 81.2±3.5 | 39.9±6.1 | 28.9±10.0 | 17.8±6.5 |
Pravastatin | 319 | 58.2±3.2 | 146.8±7.4 | 108.9±2.9 | 24.6±2.6 | 34.8±9.9 | 15.4±5.0 |