Transcript 2. Stroke and CV Risk in Asia. lipid lowering meta analysis (PPTX

On-Treatment LDL and CHD
Events in Statin Trials
30
4S - PBO
Secondary Prevention
4S - Rx
20
LIPID - PBO
CARE - PBO
LIPID - Rx
HPS - PBO
CARE - Rx
HPS - Rx
10
TNT - ATV10
PROVE-IT - PRA
TNT - ATV80
PROVE-IT - ATV80
Primary Prevention
WOSCOPS - PBO
AFCAPS - PBO
AFCAPS - Rx
WOSCOPS - Rx
ASCOT - PBO
ASCOT - Rx
0
40
(1.0)
60 70 80
(1.6) (1.8) (2.1)
100
(2.6)
120
(3.1)
140
(3.6)
160
(4.1)
180
(4.7)
200
(5.2)
LDL-C achieved, mg/dL (mmol/L)
Adapted from Rosenson RS. Expert Opin Emerg Drugs. 2004;9:269-279.
LaRosa JC et al. N Engl J Med. 2005;352:1425-1435.
2
Second Cycle of the CTT Meta-analysis:
Proportional Effects on Major Vascular
Events Per Mmol/L LDL-C Reduction
No. of events (% pa)
Statin/more
Relative risk (CI) per
mmol/L LDL-C reduction
Control/less
More vs. less statin
PROVE-IT
A to Z
TNT
IDEAL
SEARCH
Subtotal (5 trials)
406 (11.3)
257 (7.2)
889 (4.0)
938 (5.2)
1347 (3.6)
3837 (4.5)
458 (13.1)
282 (8.1)
1164 (5.4)
1106 (6.3)
1406 (3.8)
4416 (5.3)
5883 (3.1)
254 (5.4)
144 (9.0)
114 (2.7)
102 (0.5)
105 (0.5)
172 (2.2)
362 (8.1)
7136 (2.8)
7467 (4.0)
293 (6.4)
162 (10.1)
136 (3.3)
140 (0.7)
194 (1.0)
174 (2.2)
368 (8.3)
8934 (3.6)
10973 (3.2)
13350 (4.0)
0.72 (0.66 - 0.78)
P < 0.001
Statin vs. control
First cycle (14 trials)
ALLIANCE
4D
ASPEN
MEGA
JUPITER
GISSI-HF
AURORA
Subtotal (21 trials)
Total (26 trials)
99% or
95% CI
Difference between more vs. less and statin vs. control:
c 2= 4.5, p=0.03
0.78 (0.76 - 0.81)
0.5
0.75
Statin/more better
1
0.79 (0.77 - 0.81)
P < 0.001
0.78 (0.76 - 0.80)
P < 0.001
1.25
1.5
Control/less better
1
Cholesterol Treatment Trialists Collaboration. Lancet. 2010;376:1670-1681.
3
Second Cycle of the CTT Meta-analysis:
More vs Less Statin—Proportional Effects on
Major Vascular Events Per Mmol/L LDL-C Reduction
No. of events (% pa)
More statin
Less statin
Relative risk (CI) per
mmol/L LDL-C reduction
1175 (1.3%)
1380 (1.5%)
0.71 (0.58 - 0.87)
645 (0.7%)
694 (0.7%)
0.85 (0.63 - 1.15)
1725 (1.9%)
1973 (2.2%)
637 (0.7%)
731 (0.9%)
0.74 (0.65 - 0.85)
P < 0.0001
0.72 (0.55 - 0.95)
PTCA
Unspecified
1166 (1.3%)
1508 (1.8%)
0.60 (0.50 - 0.71)
447 (0.5%)
502 (0.6%)
0.78 (0.58 - 1.04)
Any coronary revascularization
2250 (2.6%)
2741 (3.2%)
440 (0.5%)
526 (0.6%)
0.66 (0.60 - 0.73)
P < 0.0001
0.69 (0.50 - 0.95)
69 (0.1%)
57 (0.1%)
1.39 (0.57 - 3.39)
63 (0.1%)
80 (0.1%)
0.63 (0.24 - 1.66)
572 (0.6%)
663 (0.7%)
3837 (4.5%)
4416 (5.3%)
0.74 (0.59 - 0.92)
P = 0.007
0.72 (0.66 - 0.78)
Nonfatal MI
CHD death
Any major coronary event
CABG
Ischemic stroke
Hemorrhagic stroke
Unknown stroke
Any stroke
Any major vascular event
(5 trials)
99% or
95% CI
0.5
0.75
More statin better
Cholesterol Treatment Trialists Collaboration. Lancet. 2010;376:1670-1681.
1
1.25
1.5
Less statin better
4
Second Cycle of the CTT Meta-analysis:
Statin vs Control—Proportional Effects on
Major Vascular Events Per Mmol/L LDL-C Reduction
No. of events (% pa)
Statin
Control
Relative risk (CI) per
mmol/L LDL-C reduction
Nonfatal MI
2310 (0.9%)
3213 (1.2%)
0.74 (0.69 - 0.78)
CHD death
Any major coronary event
1242 (0.5%)
1587 (0.6%)
0.80 (0.73 - 0.86)
3380 (1.3%)
4539 (1.7%)
CABG
816 (0.3%)
1126 (0.4%)
0.76 (0.73 - 0.79)
P < 0.001
0.76 (0.69 - 0.83)
PTCA
Unspecified
601 (0.2%)
775 (0.3%)
0.78 (0.69 - 0.89)
1686 (0.6%)
2165 (0.8%)
0.76 (0.70 - 0.83)
Any coronary revascularization
3103 (1.2%)
4066 (1.6%)
Ischemic stroke
Hemorrhagic stroke
987 (0.4%)
1225 (0.5%)
0.76 (0.73 - 0.80)
P < 0.001
0.80 (0.73 - 0.88)
188 (0.1%)
163 (0.1%)
1.10 (0.86 - 1.42)
Unknown stroke
Any stroke
555 (0.2%)
629 (0.2%)
0.88 (0.76 - 1.02)
1730 (0.7%)
2017 (0.8%)
7136 (2.8%)
8934 (3.6%)
0.85 (0.80 - 0.90)
P < 0.001
0.79 (0.77 - 0.81)
P < 0.001
Any major vascular event
(all 21 trials)
99% or
95% CI
0.5
0.75
Statin better
Cholesterol Treatment Trialists Collaboration. Lancet. 2010;376:1670-1681.
1
1.25
1.5
Control better
5
Meta-analysis of Statin Trials and
Fatal and Nonfatal Stroke
N = 165,732
Study
Active group
(%)
Control group
(%)
4.2
0.4
2.8
1.3
3.4
2.3
2.9
1.5
1.0
1.2
1.7
4.0
1.2
3.2
4.7
0.8
0.9
0.4
3.3
2.6
1.9
1.4
2.5
4.6
0.7
3.2
1.6
3.9
3.1
3.2
2.8
0.9
1.6
2.4
4.5
2.1
4.8
4.5
1.6
0.9
0.5
3.9
2.4
2.8
1.5
3.5
RR
(95% CI)
RR
(95% CI)
Primary prevention of stroke
SEARCH
JUPITER
ASPEN
MEGA
IDEAL
TNT
ALLIANCE
CARDS
PROVE-IT
A TO Z
ASCOT-LLA
ALLHAT-LLT
GREACE
HPS (with no prior CVD)
PROSPER
MIRACL
GISSI
AFCAPS/TexCAPS
LIPID (with no prior CVD)
Post-CABG
CARE (with no prior CVD)
WOSCOPS
SSSS
0.91 (0.77, 1.08)
0.52 (0.34, 0.78)
0.89 (0.56, 1.40)
0.83 (057,1.20)
0.87 (0.70, 1.08)
0.76 (0.60, 0.96)
0.90 (0.58, 1.42)
0.53 (0.31, 0.90)
1.09 (0.59, 2.01)
0.79 (0.48, 1.29)
0.73 (0.56, 0.96)
0.91 (0.76, 1.09)
0.53 (0.24, 1.18)
0.67 (0.57, 0.77)
1.04 (0.82, 1.31)
0.50 (0.25, 1.00)
1.05 (0.56, 1.96)
0.82 (0.41, 1.67)
0.84 (0.67, 1.05)
1.12 (0.58, 2.18)
0.67 (0.44, 1.01)
0.90 (0.61, 1.34)
0.72 (0.51, 1.01)
Sub-total: P < 0.0001 (heterogeneity: I2 = 26.6%, P = 0.12)
0.81 (0.75, 0.87)
Secondary prevention of stroke
SPARCL
HPS (with prior CVD
LIPID (with prior CVD)
CARE (with prior CVD)
11.2
10.3
9.5
13.5
13.1
10.4
13.3
20.0
0.85 (0.73,
0.99 (0.81,
0.72 (0.46,
0.68 (0.37,
Sub-total: P = 0.03 (heterogeneity: I2 = 0.8%, P = 0.39)
0.99
1.21)
1.12)
1.25)
0.88 (0.78, 0.99)
0.82 (0.77, 0.87
Total: P < 0.0001 (heterogeneity: I2 = 7.3%, P = 0.36)
0.1
Amarenco P et al. Lancet Neurol. 2009;8:453-463.
0.2
0.5
1
2
Log-scale
5
10
6
Meta-analysis of Statin Trials and
Stroke Mortality
Study
Active
group
(%)
Control
group
(%)
RR
(95% CI)
RR
(95% CI)
Primary prevention of stroke
SEARCH
JUPITER
CARDS
ALLHAT-LLT
GREACE
HPS
PROSPER
MIRACL
GISSI
LIPID
CARE
WOSCOPS
SSSS
0.9
0.3
0.1
1.0
0.0
0.9
0.8
0.2
0.2
0.5
0.2
0.2
0.6
1.1
0.7
0.5
1.1
0.1
1.2
0.5
0.1
0.2
0.6
0.1
0.1
0.5
0.85 (0.60, 1.21)
0.50 (0.13, 2.00)
0.14 (0.02, 1.15)
0.95 (0.65, 1.38)
0.33 (0.01, 8.17)
0.81 (0.62, 1.05)
1.58 (0.81, 3.09)
1.51 (0.25, 9.02)
1.00 (0.25, 3.98)
0.81 (0.46, 1.43)
4.99 (0.58, 42.70)
1.50 (0.42, 5.30)
1.17 (0.54, 2.52)
Sub-total: P = 0.18 (heterogeneity: I2 = 0%, P = 0.48)
0.90 (0.76, 1.05)
Secondary prevention of stroke
SPARCL
1.0
0.59 (0.36, 0.97)
1.7
Total: P = 0.10 (heterogeneity: I2 = 8.1%, P = 0.36)
0.1 0.2
Amarenco P et al. Lancet Neurol. 2009;8:453-463.
0.87 (0.73, 1.03)
0.5 1 2
Log-scale
5
10
7
Stroke Risk and LDL Lowering in
Statin Trials
N = 165,732
Relative Risk of Stroke in Active vs Control Groups
(non-log scale)
Each 1 mmol (39 mg) LDL-C reduction reduced
the risk of stroke by 21% (95% CI, 6.3–33.5%; p<0.009)
1.2
Post-CABG
1.1
PROVE-IT
PROSPER
GISSI
ALLHAT-LLT
WOSCOPS
IDEAL
ASPEN
LIPID
ALLIANCE
AFCAPS/TexCAPS
MEGA
A to Z
ASCOT-LLA
TNT HPS
SSSS
CARE
1.0
SEARCH
0.9
0.8
0.7
0.6
SPARCL-CS (-)
SPARCL
SPARCL-CS (+)
CARDS
0.5
JUPITER
GREACE
MIRACL
0.4
0
0
-10
-15
-20
-25
-30
-35
-40
-45
-50
-55
Between Group Difference in LDL-Cholesterol Reduction, %
(active minus control groups)
Amarenco P et al. Lancet Neurol. 2009;8:453-463.
8