1. Comprehensive Meta-Analysis of DES vs
Comprehensive Meta-Analysis of DES vs. BMS Randomized Trials and Registries
Ajay J. Kirtane, M.D., S.M.
Gregg W. Stone, M.D.

2. Conflict of Interest Disclosure
Ajay J. Kirtane
Past honorarium from Boston Scientific Corporation (modest)
Consultant/Speaker: Medtronic Vascular, Abbott Vascular (modest)
Gregg W. Stone
Research grants from Boston Scientific and Abbott Vascular

3. Persistent Questions: DES vs. BMS
While some of the alarm generated after ESC has been mitigated by analyses of patient-level data from the “on-label” RCTs*, there remains concern regarding DES outcomes in “off-label” patients and lesions, and with uncontrolled use
Are DES safe in higher risk off-label pts and in the unregulated environment of real-world use?
Are the benefits of DES in reducing TVR as robust in the real-world as in the RCTs, given the impact of routine angio FU and the oculostenotic reflex in many RCTs?
*Stone et al, Kastrati et al, Spaulding et al, Mauri et al
N Engl J Med 2007; 356(10).

4. Methods: Goals and Objectives (1)
We therefore sought to perform a systematic review and meta-analysis from all high quality DES vs. BMS studies
To derive summary estimates of all-cause mortality, MI, and TVR in studies with ≥1 year of follow-up
To specifically assess differences between RCT and registry safety and effiacy with regard to these endpoints

5. Methods: Inclusion Criteria
English language RCTs or registries which reported a direct comparison of DES (commercialized formulations of SES and PES only) vs. BMS.
Pre-specified criteria for each study:
≥100 patients total
Mortality reported (± MI and/or TVR)
≥1 year of follow-up reported, with the outcome assessed at the same time point in both comparator arms

6. Methods: Statistical Analysis
All analyses were performed at The Cardiovascular Research Foundation/Columbia University
Models (both reported):
Fixed effects (Inverse-Variance weighted)
Random effects (DerSimonian and Laird)*
Fixed effects model was considered the primary model if significant heterogeneity was not present; otherwise random effects was considered primary
Formal heterogeneity testing was performed using the I2 statistic; heterogeneity was defined as I2 ≥ 25%
*Weights displayed in figures are based upon the primary model used

7. All-Cause Mortality: All RCTs
8,867 patients, 21 trials
Estimate (95% CI)
Weight (%)
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Random Effects
*Fixed Effects (I2=0.0%)
0.97 (0.81,1.15)
0.97 (0.81,1.15), p=0.72
Favors DES
Favors BMS
Mean f/u 2.9 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008 7

8. All-Cause Mortality: RCTs (On-Label)
4,818 patients, 10 trials
Estimate (95% CI)
Weight (%)
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Random Effects
*Fixed Effects (I2=0.0%)
1.05 (0.84,1.30)
1.05 (0.84,1.30), p=0.69
Favors DES
Favors BMS
Mean f/u 4.0 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008 8

9. All-Cause Mortality: RCT’s (Off-Label)
4,049 patients, 12 trials
Estimate (95% CI)
Weight (%)
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Random Effects
*Fixed Effects (I2=0.0%)
0.84 (0.62,1.13)
0.84 (0.62,1.13), p=0.24
Favors DES
Favors BMS
Mean f/u 1.5 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008 9

10. All-Cause Mortality: All Registries
161,232 patients, 28 registries
Estimate (95% CI)
Weight (%)
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*Random Effects (I2=70.1%)
Fixed Effects
0.80 (0.72,0.88), p<0.001
0.83 (0.79,0.86)
Favors DES
Favors BMS
Mean f/u 2.5 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008 10

11. Ajay J. Kirtane and Gregg W. Stone, 2008
MI: All RCTs
8,850 patients, 20 trials
Estimate (95% CI)
Weight (%)
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Random Effects
*Fixed Effects (I2=3.0%)
0.94 (0.78,1.13)
0.94 (0.79,1.13), p=0.54
Favors DES
Favors BMS
Mean f/u 2.9 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008 11

12. Ajay J. Kirtane and Gregg W. Stone, 2008
MI: RCTs (On Label)
4,318 patients, 9 trials
Estimate (95% CI)
Weight (%)
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Random Effects
*Fixed Effects (I2=0.0%)
1.03 (0.81,1.30)
1.03 (0.81,1.30), p=0.82
Favors DES
Favors BMS
Mean f/u 4.4 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008 12

13. Ajay J. Kirtane and Gregg W. Stone, 2008
MI: RCT’s (Off Label)
4,532 patients, 12 trials
Estimate (95% CI)
Weight (%)
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Random Effects
*Fixed Effects (I2=25.5%)
0.77 (0.54,1.10)
0.83 (0.62,1.10), p=0.19
Favors DES
Favors BMS
Mean f/u 1.5 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008 13

14. Ajay J. Kirtane and Gregg W. Stone, 2008
MI: All Registries
129,955 patients, 24 registries
Estimate (95% CI)
Weight (%)
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*Random Effects (I2=57.9%)
Fixed Effects
0.89 (0.80,0.98), p=0.023
0.96 (0.91,1.01)
*MI is QWMI in Washington Hospital Center, RESTEM
Favors DES
Favors BMS
Mean f/u 2.5 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008 14

15. Ajay J. Kirtane and Gregg W. Stone, 2008
TVR: All RCTs
7,291 patients, 16 trials
Estimate (95% CI)
Weight (%)
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*Random Effects (I2=53.2%)
Fixed Effects
0.45 (0.37,0.54), p<0.001
0.51 (0.45,0.57)
Favors DES
Favors BMS
Mean f/u 3.2 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008 15

16. Ajay J. Kirtane and Gregg W. Stone, 2008
TVR: RCTs (On Label)
4,618 patients, 9 trials
Estimate (95% CI)
Weight (%)
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*Random Effects (I2=48.8%)
Fixed Effects
0.53 (0.43,0.65), p<0.001
0.54 (0.47,0.62)
Favors DES
Favors BMS
Mean f/u 4.2 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008 16

17. Ajay J. Kirtane and Gregg W. Stone, 2008
TVR: RCTs (Off Label)
2,673 patients, 8 trials
Estimate (95% CI)
Weight (%)
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*Random Effects (I2=47.8%)
Fixed Effects
0.38 (0.27,0.52), p<0.001
0.42 (0.34,0.52)
Favors DES
Favors BMS
Mean f/u 1.6 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008 17

18. Ajay J. Kirtane and Gregg W. Stone, 2008
TVR: All Registries
73,819 patients, 17 registries
Estimate (95% CI)
Weight (%)
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*Random Effects (I2=71.2%)
Fixed Effects
0.53 (0.47,0.61), p<0.001
0.57 (0.54,0.60)
Favors DES
Favors BMS
Mean f/u 2.2 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008 18

19. Summary: DES vs. BMS Treatment Effect Estimates
Mortality MI
TVR
RCTs
8,867 pts, trials
8,850 pts, trials
7,291 pts, trials
Fixed effects
Random effects
0.97
0.94
0.51
0.45
Registries
161,232 pts, studies
129,955 pts, studies
73,819 pts, studies
0.83
0.80
0.96
0.89
0.57
0.53
<1.0  DES better

20. Conclusions (1)
In 22 RCTs in which 9,470 pts were randomized to DES or BMS and followed for ≥1 yr, DES resulted in:
Non significant 3% and 6% reductions in mortality and MI respectively
A highly significant 55% reduction in TVR
In 30 registries in which 174,302 pts were treated with either DES or BMS and followed for ≥1 yr, DES resulted in:
A highly significant 20% reduction in mortality
A significant 11% reduction in MI
A highly significant 47% reduction in TVR

21. Conclusions (2)
The favorable results of DES from the RCT and registry analysis populations were robust and consistent for both on-label and off-label use, and for clinical f/u extending to 3-4 years
These findings, derived from more than 180,000 pts treated in 52 studies, strongly suggest that DES are safe for both on-label and off-label use, and have comparable efficacy in both RCTs and in the “real-world”