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.