1. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials
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Lancet 2010; 376: 1670–81
DOI: /S (10)

2. Second CTT cycle: more vs less intensive statin therapy
Study
Treatment comparison N
Target population
Entry lipid criteria
PROVE-IT
A 80 vs. P 40
4162
ACS
TC ≤240 mg/dL
A to Z
S 40 then S 80 vs. placebo then S 20
4497
TC ≤250 mg/dL
TNT
A 80 vs. A 10
10,001
Prior CHD
LDL-C mg/dL
TG ≤600 mg/dL
IDEAL
A 80 vs. S 20-40
8888
SEARCH
S 80 vs. S 20
12,064
TC ≥4.5 mmol/L or ≥3.5 if on statins
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3. Second CTT cycle: additional trials of statin vs control
Study
Treatment comparison N
Target population
Entry lipid criteria
MEGA
P vs. usual care
8214
Primary prevention
TC mg/dL
JUPITER
R 20 vs. placebo
17 802
Primary prevention (but CRP>2 mg/dL)
LDL-C <130 mg/dL, TG <500 mg/dL 4D
A 20 vs. placebo
1255
Type 2 DM + haemodialysis
LDL-C mg/dL
TG <1000 mg/dL
AURORA
R 10 vs. placebo
2773
Haemodialysis
None
ALLIANCE
A (until LDL <80 mg/dL) vs. usual care
2442
Prior CHD
LDL-C mg/dL on lipid lowering drugs, mg/dL if not
ASPEN
A 10 vs. placebo
2410
Type 2 DM + CHD or risk factors
LDL-C <150, TG ≤445 mg/dL with CHD; LDL-C <159, TG ≤600 mg/dL without
GISSI-HF
4574
CHF
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4. Proportional effects on MAJOR VASCULAR EVENTS unweighted for 1-year LDL-C differences
No. of events (% pa)
Statin/more
Control/less
Relative risk (CI)
More vs. less statin
PROVE-IT
406 (11.3)
458 (13.1)
A to Z
257 (7.2)
282 (8.1)
TNT
889 (4.0)
1164 (5.4)
IDEAL
938 (5.2)
1106 (6.3)
SEARCH
1347 (3.6)
1406 (3.8)
Subtotal (5 trials)
3837 (4.5)
4416 (5.3)
0.85 ( )
Statin vs. control
First cycle (14 trials)
5883 (3.1)
7467 (4.0)
0.77 ( )
ALLIANCE
254 (5.4)
293 (6.4) 4D
144 (9.0)
162 (10.1)
ASPEN
114 (2.7)
136 (3.3)
MEGA
102 (0.5)
140 (0.7)
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JUPITER
105 (0.5)
194 (1.0)
GISSI-HF
172 (2.2)
174 (2.2)
AURORA
362 (8.1)
368 (8.3)
Subtotal (21 trials)
7136 (2.8)
8934 (3.6)
0.78 ( )
Total (26 trials)
10973 (3.2)
13350 (4.0)
0.80 ( )
99% or
95% CI
0.5
0.75 1
1.25
1.5
Difference between more vs. less and statin vs. control: c 2 =
10.7, p=0.001
Statin/more better
Control/less better 1

5. MORE VS LESS STATIN – Proportional effects on MAJOR VASCULAR EVENTS unweighted for 1-year LDL-C differences
No. of events (% pa)
More statin
Less statin
Relative risk (CI)
Nonfatal MI
1175 (1.3%)
1380 (1.5%)
0.85 ( )
CHD death
645 (0.7%)
694 (0.7%)
0.93 ( )
Any major coronary event
1725 (1.9%)
1973 (2.2%)
0.87 ( )
CABG
637 (0.7%)
731 (0.9%)
0.86 ( )
PTCA
1166 (1.3%)
1508 (1.8%)
0.76 ( )
Unspecified
447 (0.5%)
502 (0.6%)
0.87 ( )
Any coronary revascularisation
2250 (2.6%)
2741 (3.2%)
0.81 ( )
Ischaemic stroke
440 (0.5%)
526 (0.6%)
0.84 ( )
Haemorrhagic stroke
69 (0.1%)
57 (0.1%)
1.21 ( )
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Unknown stroke
63 (0.1%)
80 (0.1%)
0.79 ( )
Any stroke
572 (0.6%)
663 (0.7%)
0.86 ( )
Any major vascular event
3837 (4.5%)
4416 (5.3%)
0.85 ( )
99% or
95% CI
0.4
0.6
0.8 1
1.2
1.4
More statin better
Less statin better

6. mmol/L LDL-C reduction
Proportional effects on MAJOR VASCULAR EVENTS per mmol/L LDL-C reduction
No. of events (% pa)
Relative risk (CI) per
mmol/L LDL-C reduction
Statin/more
Control/less
More vs. less statin
PROVE-IT
406 (11.3)
458 (13.1)
A to Z
257 (7.2)
282 (8.1)
TNT
889 (4.0)
1164 (5.4)
IDEAL
938 (5.2)
1106 (6.3)
SEARCH
1347 (3.6)
1406 (3.8)
Subtotal (5 trials)
3837 (4.5)
4416 (5.3)
0.72 ( )
Statin vs. control
First cycle (14 trials)
5883 (3.1)
7467 (4.0)
0.78 ( )
ALLIANCE
254 (5.4)
293 (6.4) 4D
144 (9.0)
162 (10.1)
ASPEN
114 (2.7)
136 (3.3)
MEGA
102 (0.5)
140 (0.7)
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JUPITER
105 (0.5)
194 (1.0)
GISSI-HF
172 (2.2)
174 (2.2)
AURORA
362 (8.1)
368 (8.3)
Subtotal (21 trials)
7136 (2.8)
8934 (3.6)
0.79 ( )
Total (26 trials)
10973 (3.2)
13350 (4.0)
0.78 ( )
99% or
95% CI
0.5
0.75 1
1.25
1.5
Difference between more vs. less and statin vs. control: c 2 =
4.5, p=0.03
Statin/more better
Control/less better 1

7. mmol/L LDL-C reduction
MORE VS LESS STATIN – Proportional effects on MAJOR VASCULAR EVENTS per mmol/L LDL-C reduction
No. of events (% pa)
Relative risk (CI) per
mmol/L LDL-C reduction
More statin
Less statin
Nonfatal MI
1175 (1.3%)
1380 (1.5%)
0.71 ( )
CHD death
645 (0.7%)
694 (0.7%)
0.85 ( )
Any major coronary event
1725 (1.9%)
1973 (2.2%)
0.74 ( )
CABG
637 (0.7%)
731 (0.9%)
0.72 ( )
PTCA
1166 (1.3%)
1508 (1.8%)
0.60 ( )
Unspecified
447 (0.5%)
502 (0.6%)
0.78 ( )
Any coronary revascularisation
2250 (2.6%)
2741 (3.2%)
0.66 ( )
Ischaemic stroke
440 (0.5%)
526 (0.6%)
0.69 ( )
Haemorrhagic stroke
69 (0.1%)
57 (0.1%)
1.39 ( )
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Unknown stroke
63 (0.1%)
80 (0.1%)
0.63 ( )
Any stroke
572 (0.6%)
663 (0.7%)
0.74 ( )
Any major vascular event
3837 (4.5%)
4416 (5.3%)
0.72 ( )
99% or
95% CI
0.4
0.6
0.8 1
1.2
1.4
More statin better
Less statin better

8. mmol/L LDL-C reduction
STATIN VS CONTROL – Proportional effects on MAJOR VASCULAR EVENTS per mmol/L LDL-C reduction
No. of events (% pa)
Relative risk (CI) per
mmol/L LDL-C reduction
Statin
Control
Nonfatal MI
2310 (0.9%)
3213 (1.2%)
0.74 ( )
CHD death
1242 (0.5%)
1587 (0.6%)
0.80 ( )
Any major coronary event
3380 (1.3%)
4539 (1.7%)
0.76 ( )
CABG
816 (0.3%)
1126 (0.4%)
0.76 ( )
PTCA
601 (0.2%)
775 (0.3%)
0.78 ( )
Unspecified
1686 (0.6%)
2165 (0.8%)
0.76 ( )
Any coronary revascularisation
3103 (1.2%)
4066 (1.6%)
0.76 ( )
Ischaemic stroke
987 (0.4%)
1225 (0.5%)
0.80 ( )
Haemorrhagic stroke
188 (0.1%)
163 (0.1%)
1.10 ( )
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Unknown stroke
555 (0.2%)
629 (0.2%)
0.88 ( )
Any stroke
1730 (0.7%)
2017 (0.8%)
0.85 ( )
Any major vascular event
7136 (2.8%)
8934 (3.6%)
0.79 ( )
99% or
95% CI
0.4
0.6
0.8 1
1.2
1.4
Statin better
Control better

9. Proportional effects on MAJOR VASCULAR EVENTS per mmol/L LDL-C reduction, by baseline prognostic factors
No. of patients (% pa)
Relative risk (CI) per
mmol/l LDL-C reduction
Statin/more
Control/less
Previous coronary disease:
CHD
8395 (4.5%)
10123 (5.6%)
0.79 ( )
Non-CHD vascular
674 (3.1%)
802 (3.7%)
0.81 ( )
None
1904 (1.4%)
2425 (1.8%)
0.75 ( )
Diabetes:
Type 1 diabetes
145 (4.5%)
192 (6.0%)
0.77 ( )
Type 2 diabetes
2494 (4.2%)
2920 (5.1%)
0.80 ( )
No diabetes
8272 (3.2%)
10163 (4.0%)
0.78 ( )
Sex:
Male
8712 (3.5%)
10725 (4.4%)
0.77 ( )
Female
2261 (2.5%)
2625 (2.9%)
0.83 ( )
Age (years)
£65
6056 (2.9%)
7455 (3.6%)
0.78 ( )
>65, £75
4032 (3.7%)
4908 (4.6%)
0.78 ( )
>75
885 (4.8%)
987 (5.4%)
0.84 ( )
Body mass index (kg/m2):
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<25
3030 (3.0%)
3688 (3.7%)
0.79 ( )
³25,< 30
5033 (3.3%)
6125 (4.1%)
0.78 ( )
³30
2732 (3.3%)
3331 (4.1%)
0.78 ( )
Smoking status:
Current smokers
2268 (3.6%)
2896 (4.7%)
0.78 ( )
Non-smokers
8703 (3.1%)
10452 (3.9%)
0.78 ( )
Total
10973 (13.0%)
13350 (15.8%)
0.78 ( )
99% or
95% CI
0.4
0.6
0.8 1
1.2
1.4
Statin/more
better
Control/less
better

10. Proportional effects on MAJOR VASCULAR EVENTS per mmol/L LDL-C reduction, by baseline prognostic factors
No. of patients (% pa)
Relative risk (CI) per
mmol/l LDL-C reduction
Statin/more
Control/less
Treated hypertension:
Yes
6176 (3.7%)
7350 (4.5%)
0.80 ( ) No
4543 (2.7%)
5707 (3.5%)
0.76 ( )
Systolic blood pressure (mm Hg):
<140
5470 (3.2%)
6500 (3.8%)
0.80 ( )
³140,< 160
3145 (3.0%)
4049 (3.9%)
0.75 ( )
³160
2067 (3.6%)
2473 (4.5%)
0.79 ( )
Diastolic blood pressure (mm Hg):
<80
4558 (3.5%)
5306 (4.2%)
0.81 ( )
³80,< 90
3670 (3.0%)
4587 (3.8%)
0.77 ( )
³90
2452 (3.0%)
3128 (3.9%)
0.77 ( )
Estimated GFR (mL/min/1.73m2):
< 60
2712 (4.1%)
3354 (5.1%)
0.77 ( )
³60, < 90
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6161 (3.2%)
7540 (4.0%)
0.78 ( )
³90
1315 (2.5%)
1571 (3.0%)
0.77 ( )
HDL-C (mmol/L):
£1.0
5032 (4.0%)
6165 (5.0%)
0.78 ( )
>1.0, £1.3
3656 (3.1%)
4452 (3.9%)
0.77 ( )
>1.3
2199 (2.4%)
2633 (2.9%)
0.80 ( )
Total
10973 (13.0%)
13350 (15.8%)
0.78 ( )
99% or
95% CI
0.4
0.6
0.8 1
1.2
1.4
Statin/more
better
Control/less
better

11. mmol/L LDL-C reduction
Proportional effects on MAJOR VASCULAR EVENTS per mmol/L LDL-C reduction, by baseline LDL-C
No. of events (% pa)
Relative risk (CI) per
mmol/L LDL-C reduction
Statin/more
Control/less
More vs less statin
<2.0
704 (17.9%)
795 (20.2%)
0.71 ( )
³2,<2.5
1189 (18.4%)
1317 (20.8%)
0.77 ( )
³2.5,<3.0
1065 (20.1%)
1203 (22.2%)
0.81 ( )
³3,<3.5
517 (20.4%)
633 (25.8%)
0.61 ( )
³3.5
303 (23.9%)
398 (31.2%)
0.64 ( )
Total
3837 (19.4%)
4416 (22.3%)
0.72 ( )
Statin vs control
<2.0
206 (9.0%)
217 (9.7%)
0.87 ( )
³2,<2.5
339 (7.7%)
412 (9.1%)
0.77 ( )
³2.5,<3.0
801 (8.2%)
1022 (10.5%)
0.76 ( )
³3,<3.5
1490 (10.8%)
1821 (13.3%)
0.77 ( )
³3.5
4205 (12.6%)
5338 (15.9%)
0.80 ( )
Total
7136 (11.0%)
8934 (13.8%)
0.79 ( )
All trials
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<2.0
910 (14.7%)
1012 (16.4%)
0.78 ( )
³2,<2.5
1528 (14.0%)
1729 (15.9%)
0.77 ( )
³2.5,<3.0
1866 (12.4%)
2225 (14.7%)
0.77 ( )
³3,<3.5
2007 (12.3%)
2454 (15.2%)
0.76 ( )
³3.5
4508 (13.0%)
5736 (16.5%)
0.80 ( )
Total
10973 (13.0%)
13350 (15.8%)
0.78 ( )
99% or
95% CI
0.5
0.75 1
1.25
1.5
Statin/more better
Control/less better

12. Proportional effects on CAUSE-SPECIFIC MORTALITY per mmol/L LDL-C reduction
No. of deaths(% pa)
Relative risk (CI) per
mmol/L LDL-C reduction
Statin/more
Control/less
Vascular causes
CHD
1887 (0.5%)
2281 (0.6%)
0.80 ( )
Other cardiac
1446 (0.4%)
1603 (0.4%)
0.89 ( )
All cardiac
3333 (0.9%)
3884 (1.1%)
0.84 ( )
Ischaemic stroke
153 (0.0%)
139 (0.0%)
1.04 ( )
Haemorrhagic stroke
102 (0.0%)
89 (0.0%)
1.12 ( )
Unknown stroke
228 (0.1%)
273 (0.1%)
0.85 ( )
Stroke
483 (0.1%)
501 (0.1%)
0.96 ( )
Other vascular
404 (0.1%)
409 (0.1%)
0.98 ( )
Any vascular
4220 (1.2%)
4794 (1.3%)
0.86 ( )
Non-vascular
Cancer
1781 (0.5%)
1798 (0.5%)
0.99 ( )
Respiratory
224 (0.1%)
237 (0.1%)
0.88 ( )
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Trauma
127 (0.0%)
127 (0.0%)
0.98 ( )
Other non-vascular
811 (0.2%)
832 (0.2%)
0.96 ( )
Any non-vascular
2943 (0.8%)
2994 (0.8%)
0.97 ( )
Unknown death
479 (0.1%)
539 (0.1%)
0.87 ( )
Any death
7642 (2.1%)
8327 (2.3%)
0.90 ( )
99% or
95% CI
0.4
0.6
0.8 1
1.2
1.4
Statin/more better
Control/less better

13. mmol/L LDL-C reduction
Proportional effects on SITE SPECIFIC CANCER per mmol/L LDL-C reduction
No. of first cancers (% pa)
Relative risk (CI) per
mmol/L LDL-C reduction
Statin/more
Control/less
Gastrointestinal
1166 (0.3%)
1194 (0.3%)
0.97 ( )
Genitourinary
1596 (0.5%)
1645 (0.5%)
0.97 ( )
Respiratory
813 (0.2%)
814 (0.2%)
1.00 ( )
Female breast
267 (0.3%)
241 (0.3%)
1.07 ( )
Haematological
305 (0.1%)
291 (0.1%)
1.04 ( )
Melanoma
159 (0.0%)
142 (0.0%)
1.14 ( )
Other/unknown
754 (0.2%)
737 (0.2%)
1.04 ( )
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Any
5060 (1.4%)
5064 (1.4%)
1.00 ( )
99% or
95% CI
0.4
0.6
0.8 1
1.2
1.4
Statin/more better
Control/less better