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Online Appendix for the following JACC article
TITLE: A Meta-Analysis Reporting Effects of Angiotensin Converting Enzyme Inhibitors and
Angiotensin Receptor Blockers in Patients Without Heart Failure
AUTHORS: Gianluigi Savarese, MD*, Pierluigi Costanzo, MD*, John George Franklin Cleland,
MD, Enrico Vassallo, MD, Giuseppe Rosano, MD, PhD, Pasquale Perrone-Filardi, MD, PhD
APPENDIX
Potential effect modifier
Composite
Outcome
MI Cardiovascula
r Death
All Cause
Death
Stroke Heart
Failure new
onset
Diabetes
Mellitus new
onset
Chang
e in
tau2
P
Chang
e in
tau2 P
Change
in tau2 P
Chang
e in
tau2 P
Chang
e in
tau2 P
Chang
e in
tau2 P
Chang
e in
tau2 P
ARBs
Age
-0.59 0.57
2 1.61
0.14
7
-0.87 0.416 -0.54 0.60
1
-1.23 0.27
3
2.54 0.05
2
-0.20 0.85
7
Women
0.22 0.83
2 0.38
0.71
1
0.74 0.487 -0.62 0.54
6
-1.94 0.11
0
0.12 0.91
1
-0.53 0.65
0
BMI
0.80 0.44
5 -0.72
0.49
4
1.56 0.170 -0.17 0.87
2
0.05 0.96
3
-0.34 0.74
6
-0.09 0.93
8
Hypertension
0.48 0.64
9 -1.67
0.14
0
1.05 0.340 0.45 0.66
4
0.97 0.38
5
-2.31 0.06
9
0.48 0.67
8
Diabetes
-0.05 0.96
2 -2.05
0.07
4
1.01 0.351 1.44 0.18
0
1.19 0.28
6
-2.39 0.06
2
0.59 0.61
5
Coronary artery disease
-0.07 0.94
3 1.71
0.12
5
-0.98 0.357 -1.88 0.09
7
-0.08 0.94
2
-0.89 0.42
3
1.52 0.37
0
B Blocker 0.17 0.86 -0.33 0.75 0.91 0.413 0.20 0.84 -1.08 0.36 1.08 0.32 0.78 0.57
9 5 9 0 9 9
Aspirin
-0.40 0.71
9 -0.01
0.99
3
0.16 0.889 1.53 0.22
3
0.31 0.80
6
0.98 0.43
2
NA NA
Statin
0.25 0.81
4 -1.41
0.21
7
0.37 0.732 1.03 0.35
1
1.10 0.35
2
0.39 0.72
6
0.82 0.49
9
Diuretic
-0.84 0.44
6 -1.47
0.21
6
1.62 0.246 -0.03 0.97
7
-1.52 0.26
7
-2.39 0.09
7
0.42 0.74
9
Calcium Channel Blocker
-1.20 0.29
6 -1.69
0.16
6
0.76 0.502 0.20 0.85
3
-1.44 0.24
7
-1.37 0.24
1
0.77 0.58
1
Systolic Blood Pressure
baseline
-0.07 0.94
8 0.35
0.74
1
0.08 0.943 -0.05 0.96
1
-0.52 0.64
1
-2.02 0.11
3
-0.47 0.68
3
Diastolic Blood Pressure
baseline
0.30 0.77
1 1.08
0.32
3
0.08 0.939 -0.17 0.87
2
-0.44 0.69
0
0.06 0.95
4
-0.63 0.59
4
Delta Systolic Blood
Pressure
0.33 0.75
1 0.38
0.71
6
0.85 0.442 -1.21 0.26
4
-1.36 0.26
8
-1.38 0.23
9
-0.58 0.61
9
Delta Diastolic Blood
Pressure
0.34 0.74
2 0.66
0.53
4
0.72 0.509 -1.29 0.23
8
-1.42 0.25
1
-0.99 0.38
0
-0.59 0.61
3
Quality of trial
0.90 0.39
3 0.18
0.86
4
0.34 0.748 0.09 0.93
2
0.74 0.49
2
1.82 0.12
9
0.13 0.91
2
Event rate placebo -0.47 0.65 0.18 0.85 -0.62 0.557 -0.10 0.92 0.32 0.76 -1.94 0.11 0.80 0.50
1 9 1 5 0 5
ACE-Is
Age
-0.87 0.40
2 -0.09
0.92
9
-0.95 0.362 0.41 0.69
0
-0.25 0.81
1
0.33 0.74
8
-1.50 0.23
1
Women
0.49 0.63
7 0.05
0.96
4
0.71 0.497 0.69 0.50
6
-0.91 0.38
4
2.05 0.08
0
0.22 0.84
3
BMI
2.25 0.26
6 0.18
0.88
6
1.04 0.487 2.23 0.26
9
2.32 0.25
9
-0.25 0.84
3
NA NA
Hypertension
1.16 0.27
7 0.22
0.83
3
1.32 0.220 0.97 0.35
7
-0.22 0.83
4
1.33 0.23
3
-1.68 0.19
2
Diabetes
1.23 0.24
9 0.29
0.77
6
0.76 0.465 1.13 0.28
6
1.20 0.26
4
0.64 0.54
4
-1.96 0.14
5
Coronary artery disease
-1.27 0.25
9 -0.80
0.45
2
0.44 0.668 -0.34 0.74
5
0.01 0.99
1
1.01 0.38
8
0.92 0.52
6
B Blocker
0.09 0.92
7 -0.51
0.62
2
1.27 0.241 0.43 0.68
1
1.63 0.14
7
-2.12 0.08
8
0.08 0.94
4
Aspirin
-1.45 0.18
5 -0.64
0.54
1
-1.11 0.298 -1.83 0.10
5
-0.66 0.53
1
-1.19 0.27
8
-0.30 0.78
2
Statin
0.06 0.95
2 -0.07
0.94
8
0.74 0.481 -0.18 0.85
9
0.09 0.93
3
-1.26 0.25
4
0.09 0.93
1
Diuretic
-0.22 0.83
9 -0.58
0.59
4
1.32 0.257 0.12 0.91
1
-0.06 0.95
2
1.15 0.33
3
-0.99 0.42
8
Calcium Channel Blocker
-0.12 0.90
8 -0.10
0.92
4
-1.13 0.291 -0.79 0.45
3
-0.42 0.71
6
-0.56 0.60
0
-1.40 0.25
7
Systolic Blood Pressure
baseline
-0.14 0.89
0 -1.12
0.28
7
0.17 0.867 1.19 0.25
8
-0.12 0.90
6
-0.24 0.81
8
0.01 0.99
4
Diastolic Blood Pressure
baseline
-0.22 0.82
8 -1.23
0.24
5
0.29 0.778 0.91 0.38
1
-0.36 0.73
1
-0.70 0.50
4
1.20 0.31
7
Delta Systolic Blood
Pressure
-0.31 0.76
1 -0.54
0.60
4
-0.64 0.540 -0.99 0.35
0
0.56 0.59
1
-1.15 0.29
4
1.47 0.28
0
Delta Diastolic Blood
Pressure
-0.54 0.60
7 -0.50
0.62
9
-0.86 0.417 -1.03 0.33
3
0.56 0.59
1
-1.04 0.33
8
2.24 0.15
4
Quality of trial
2.14 0.12
2
2.71 0.07
3
0.42 0.703 -0.56 0.61
2
0.75 0.50
6
0.28 0.79
9
-0.04 0.97
0
Event rate placebo
-1.32 0.21
6
-0.55 0.59
7
-1.15 0.275 -0.31 0.76
6
-1.77 0.11
1
0.16 0.87
7
-1.05 0.37
1
Online Appendix Table 1. Influence analysis of potential effect modifiers on the outcomes. ACE-I: Angiotensin Converting Enzyme Inhibitor; ARB: Angiotensin Receptor Blocker; MI: Myocardial Infarction; NA: Not Available.
Online Appendix Figure 1. Odds ratios (OR) of cardiovascular death. Solid squares represent ORs in
trials and have a size proportional to the number of events. The 95% confidence intervals (CI) for
individual trials are denoted by lines and those for the pooled ORs by empty diamonds.
Online Appendix Figure 2. Odds ratios (OR) of myocardial infarction. Solid squares represent ORs in
trials and have a size proportional to the number of events. The 95% confidence intervals (CI) for
individual trials are denoted by lines and those for the pooled odd ratios by empty diamonds.
Online Appendix Figure 3. Odds ratios (OR) of stroke or TIA. Solid squares represent ORs in trials and
have a size proportional to the number of events. The 95% confidence intervals (CI) for individual trials
are denoted by lines and those for the pooled ORs by empty diamonds.
Online Appendix Figure 4. Odds ratios (OR) of new onset heart failure. Solid squares represent ORs in
trials and have a size proportional to the number of events. The 95% confidence intervals (CI) for
individual trials are denoted by lines and those for the pooled ORs by empty diamonds.
Online Appendix Figure 5. Odds ratios (OR) of new onset diabetes mellitus. Solid squares represent
ORs in trials and have a size proportional to the number of events. The 95% confidence intervals (CI) for
individual trials are denoted by lines and those for the pooled ORs by empty diamonds.
Online Appendix Figure 6. Odds ratios (OR) of composite outcome in each drug category group. Solid
squares represent ORs in trials and have a size proportional to the number of events. The 95% confidence
intervals (CI) for individual trials are denoted by lines and those for the pooled ORs by empty diamonds.