The Impact of Revascularization
on Mortality in Patients with NonAcute Coronary Artery Disease
Allen Jeremias MD MSc, Sanjay Kaul MD, Luis Gruberg
MD, Todd K. Rosengart MD, David L. Brown MD
Divisions of Cardiovascular Medicine and Cardiothoracic Surgery
Stony Brook University Medical Center; Cedars Sinai Medical Center,
UCLA
Background
• Coronary artery revascularization has been shown to
significantly reduce the incidence of death and MI in
the setting of acute coronary syndromes
• However, most studies evaluating revascularization
therapy in patients with stable CAD found no difference
in mortality or MI when compared with Med Rx alone
• None of these studies were adequately powered to detect
mortality differences
Objectives
• To compare coronary revascularization with Med Rx alone
with respect to mortality and MI in patients with stable CAD
• Since surgical and percutaneous revascularization
therapies have repeatedly been found to be equivalent in
preventing death or MI, we conducted a systematic review
and meta-analysis of all randomized clinical trials that
compared the effect of coronary revascularization by either
PCI or CABG to Med Rx alone
Methods
Search Strategy
• Medline and Cochrane Central Register of Controlled Trials
databases were searched
• Studies published between 1977 and May 2007
• Search terms: coronary revascularization, balloon angioplasty,
stent, coronary artery bypass grafting, medical therapy, angina,
stable, coronary artery disease
• Study eligibility assessed by 2 authors; disagreements resolved by
consensus with a third author
Methods
Inclusion Criteria
• Prospective, randomized trials of coronary revascularization vs. Med Rx
alone in patients with stable CAD
• Acute coronary syndromes excluded but stable patients following a
completed MI included
• Studies included irrespective of presence of ischemia or any functional
assessment of hemodynamic significance of a coronary stenosis
• Outcomes of death or nonfatal MI with minimum follow-up of 1 year
• Multiple study designs accepted:
2 arm randomization to PCI/CABG vs medical therapy
Any revascularization strategy vs medical therapy
3 arm randomization to PCI vs CABG vs medical therapy
Methods
Endpoints
• Endpoint definitions were those used in individual trials
• All-cause mortality was death from any cause (cardiac or
noncardiac) and was preferentially used unless only cardiac
deaths were reported
• MI was defined as elevation of serum markers of myocardial
necrosis along with EKG changes
• Endpoints were extracted from each trial at the reported
follow-up closest to 5-year mark
Methods
Statistical Analysis
• Methods based on odds ratios (OR) were used to calculate the OR
for death and nonfatal MI
• The Q statistic failed to indicate statistical heterogeneity (P=0.15)
• However, given vast differences in trials included, a summary OR
was calculated using a random-effects model and 95%
confidence intervals (CI) for each study endpoint
• Cumulative meta-analysis was performed by sequentially adding
studies one at a time according to date of publication (from
earliest to latest)
Results
• 28 studies published from 1977-2007 met inclusion criteria
• Revascularization modality:
PCI vs. Med Rx in 17 studies
CABG vs. Med Rx in 6 studies
PCI or CABG (non-randomized) vs. Med Rx in 3 studies
PCI or CABG (randomized) vs. Med Rx in 2 studies
• Total of 13,121 patients enrolled
6476 revascularization
6645 medical therapy alone
• Follow-up ranged from 1 to 10 years with median of 3 years
Results
Quantitative Analysis
• 511 deaths among the 6476 patients in the
revascularization group (7.9%)
• 649 deaths among the 6645 patients in the medical therapy
group (9.8%)
• Number needed to treat to prevent 1 death is 53
Revascularization vs. Med Rx on Mortality
Study name
Study Name
Mathur et al
Kloster et al
ECSS
Norris et al
CASS
VA Cooperative Study
ACME-1
TOPS
Sievers et al
MASS I (PCI)
MASS I (CABG)
ACIP
RITA-2
ACME-2
DANAMI
Dakik et al
Horie et al
AVERT
TOAT
Bech et al
TIME
ALKK
MASS II (CABG)
MASS II (PCI)
DECOPI
OAT
INSPIRE
SWISSI II
COURAGE
Combined
Statistics for each study
PetoOR
odds ratio
0.79
0.45
0.42
1.22
0.61
0.74
1.11
0.14
0.14
1.00
0.36
0.31
1.02
0.86
0.82
1.16
0.21
0.93
2.12
0.51
1.12
0.36
0.76
0.95
0.83
1.04
1.90
0.30
0.90
0.74
Lower
Lower
Limit
limit
0.32
0.14
0.27
0.35
0.35
0.51
0.52
0.00
0.00
0.31
0.09
0.13
0.66
0.32
0.43
0.07
0.04
0.06
0.21
0.10
0.68
0.15
0.44
0.56
0.31
0.76
0.20
0.13
0.64
0.63
Peto odds ratio and 95% CI
Upper
Upper
Limit
limit
Odds Ratio and 95% CI
1.96
1.50
0.64
4.26
1.07
1.07
2.37
7.31
6.82
3.25
1.49
0.76
1.59
2.32
1.53
19.41
1.11
14.90
21.13
2.58
1.86
0.84
1.32
1.62
2.23
1.42
18.51
0.66
1.27
0.87
0.01
0.1
Fav ours A
1
Favors Revasc.
10
Fav ours B
100
Favors Med Rx
Cumulative OR for Mortality
Study name
Cumulativ e statistics
Lower
Study Name
Mathur et al
Kloster et al
ECSS
Norris et al
CASS
VA Cooperative Study
ACME-1
TOPS
Sievers et al
MASS I (PCI)
MASS I (CABG)
ACIP
RITA-2
ACME-2
DANAMI
Dakik et al
Horie et al
AVERT
TOAT
Bech et al
TIME
ALKK
MASS II (CABG)
MASS II (PCI)
DECOPI
OAT
INSPIRE
SWISSI II
COURAGE
Combined
Point
Lower
Limit
limit
0.79
0.64
0.47
0.54
0.53
0.61
0.65
0.65
0.64
0.65
0.64
0.61
0.66
0.67
0.69
0.69
0.68
0.68
0.68
0.68
0.72
0.69
0.70
0.72
0.72
0.75
0.76
0.73
0.74
0.74
0.32
0.31
0.32
0.35
0.40
0.47
0.49
0.49
0.49
0.51
0.51
0.48
0.52
0.53
0.55
0.56
0.55
0.55
0.56
0.56
0.59
0.57
0.58
0.60
0.61
0.64
0.64
0.61
0.63
0.63
OR
Cumulativ e peto odds ratio (95% CI)
Upper
Cumulative Odds Ratio and 95% CI
Upper
Limit
limit
1.96
1.33
0.68
0.84
0.72
0.79
0.86
0.84
0.82
0.82
0.80
0.78
0.86
0.86
0.85
0.85
0.84
0.83
0.84
0.83
0.88
0.85
0.84
0.86
0.86
0.89
0.89
0.87
0.87
0.87
0.01
0.1
Fav ours A
Favors Revasc.
1
10
Fav ours B
Favors Med Rx
100
CABG vs. Med Rx on Mortality
Study name
Study Name
Mathur et al
Kloster et al
ECSS
Norris et al
CASS
VA Cooperative Study
MASS I (CABG)
MASS II (CABG)
Combined
Statistics for each study
Peto odds ratio and 95% CI
Lower Upper
Upper
Peto
Lower
OR
Limit
Limit
odds ratio limit
limit
Odds Ratio and 95% CI
0.79
0.45
0.42
1.22
0.61
0.74
0.36
0.76
0.62
0.32
0.14
0.27
0.35
0.35
0.51
0.09
0.44
0.50
1.96
1.50
0.64
4.26
1.07
1.07
1.49
1.32
0.77
0.01
0.1
Favours A
Favors Revasc.
1
10
100
Favours
B
Favors Med Rx
PCI vs. Med Rx on Mortality
Study name
Study Name
ACME-1
TOPS
Sievers et al
MASS I (PCI)
ACIP
RITA-2
ACME-2
DANAMI
Dakik et al
Horie et al
AVERT
TOAT
Bech et al
TIME
ALKK
MASS II (PCI)
DECOPI
OAT
INSPIRE
SWISSI II
COURAGE
Combined
Statistics for each study
Peto
OR
odds ratio
1.11
0.14
0.14
1.00
0.31
1.02
0.86
0.82
1.16
0.21
0.93
2.12
0.51
1.12
0.36
0.95
0.83
1.04
1.90
0.30
0.90
0.82
Lower
Lower
Limit
limit
0.52
0.00
0.00
0.31
0.13
0.66
0.32
0.43
0.07
0.04
0.06
0.21
0.10
0.68
0.15
0.56
0.31
0.76
0.20
0.13
0.64
0.67
Peto odds ratio and 95%CI
Upper
Upper
Limit
limit
Odds Ratio and 95% CI
2.37
7.31
6.82
3.25
0.76
1.59
2.32
1.53
19.41
1.11
14.90
21.13
2.58
1.86
0.84
1.62
2.23
1.42
18.51
0.66
1.27
1.00
0.01
0.1
Favours A
Favors Revasc.
1
10
Favours B
Favors Med Rx
100
Results
Myocardial Infarction
• Nonfatal MI rate reported in 26 trials that randomized
11,768 patients
• MI rate was 8.4% in the revascularization group
• MI rate was 8.9% in the medical therapy group
Revascularization vs. Med Rx on MI
Study name
Study Name
Mathur et al
Kloster et al
Norris et al
CASS
ACME-1
TOPS
Sievers et al
MASS I (PCI)
MASS I (CABG)
ACIP
RITA-2
ACME-2
DANAMI
Dakik et al
Horie et al
AVERT
TOAT
Bech et al
TIME
ALKK
Hambrecht et al
MASS II (CABG)
MASS II (PCI)
DECOPI
OAT
INSPIRE
SWISSI II
COURAGE
Combined
Statistics for each study
Peto
OR
odds ratio
Lower
Lower
Limit
limit
Upper
Upper
Limit
limit
0.61
1.25
1.00
0.93
0.87
8.78
1.98
1.35
1.03
0.74
1.44
0.98
0.51
9.15
0.35
1.16
3.04
7.47
0.96
0.83
7.54
0.52
0.70
1.42
1.45
0.68
0.25
1.12
0.92
0.21
0.45
0.36
0.64
0.29
1.46
0.20
0.30
0.20
0.32
0.84
0.29
0.33
0.55
0.09
0.31
0.41
0.77
0.48
0.35
0.15
0.28
0.40
0.24
0.96
0.21
0.13
0.87
0.81
1.74
3.44
2.76
1.35
2.67
52.92
19.53
6.12
5.25
1.73
2.48
3.25
0.81
152.61
1.32
4.36
22.66
72.77
1.93
1.98
379.98
0.94
1.25
8.34
2.17
2.18
0.47
1.45
1.05
Peto odds ratio and 95% CI
Odds Ratio and 95% CI
0.01
0.1
Favours A
Favors
Revasc.
1
10
Favours B
Favors
Med Rx
100
Limitations
• No access to individual patient-level data
• Data extracted from randomized clinical trials may not be
representative of patients actually seen in clinical practice
• Most studies performed during time of rapid improvements in
both medical and revascularization therapies, including use of
internal mammary artery for bypass grafting and coronary
stents
Conclusions
• Coronary artery revascularization by either CABG or PCI for
stable CAD is associated with a significant reduction in
mortality
• Mortality benefit apparent after inclusion of only 3 trials
• Revascularization therapy does not reduce the incidence of
non-fatal MI