Comprehensive Meta-Analysis of DES vs. BMS Randomized Trials and Registries

Columbia University Medical CenterColumbia University Medical CenterThe Cardiovascular Research FoundationThe Cardiovascular Research Foundation

Comprehensive Meta-Analysis Comprehensive Meta-Analysis

of DES vs. BMS Randomized of DES vs. BMS Randomized

Trials and RegistriesTrials and Registries

Ajay J. Kirtane, M.D., S.M.Ajay J. Kirtane, M.D., S.M. Gregg W. Stone, M.D.Gregg W. Stone, M.D.

Conflict of Interest Disclosure

• Ajay J. Kirtane Past honorarium from Boston Scientific

Corporation (modest) Consultant/Speaker: Medtronic Vascular,

Abbott Vascular (modest)

• Gregg W. StoneGregg W. Stone Research grants from Boston Scientific Research grants from Boston Scientific

and Abbott Vascularand Abbott Vascular

Persistent Questions: DES vs. BMS

• While some of the alarm generated after ESC 2006 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 alN Engl J Med 2007; 356(10).

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

Methods: Inclusion Criteria

• English language RCTs or registries which English language RCTs or registries which reported a reported a direct comparison direct comparison of DES of DES (commercialized formulations of SES and PES (commercialized formulations of SES and PES only) vs. BMS. only) vs. BMS.

• Pre-specified criteria for each study: Pre-specified criteria for each study:

≥≥100 patients total100 patients total

Mortality reported (± MI and/or TVR)Mortality reported (± MI and/or TVR)

≥≥1 year of follow-up reported, with the outcome 1 year of follow-up reported, with the outcome assessed at the same time point in both assessed at the same time point in both comparator armscomparator arms

Methods: Statistical Analysis

• All analyses were performed at The Cardiovascular All analyses were performed at The Cardiovascular Research Foundation/Columbia UniversityResearch Foundation/Columbia University

• Models (both reported):Models (both reported):

• Fixed effects (Inverse-Variance weighted)Fixed effects (Inverse-Variance weighted)

• Random effects (DerSimonian and Laird)*Random effects (DerSimonian and Laird)*

• Fixed effects model was considered the primary Fixed effects model was considered the primary model if significant heterogeneity was not model if significant heterogeneity was not present; otherwise random effects was present; otherwise random effects was considered primaryconsidered primary

• Formal heterogeneity testing was performed using Formal heterogeneity testing was performed using the Ithe I22 statistic; heterogeneity was defined as I statistic; heterogeneity was defined as I22 ≥ 25% ≥ 25%

*Weights displayed in figures are based upon the primary model used*Weights displayed in figures are based upon the primary model used

All-Cause Mortality: All RCTsAll-Cause Mortality: All RCTs

I-V Overall (I-squared = 0.0%, p = 0.918)

BASKET (SES only)

TAXUS II

HAAMU-STENTSeville

Ortolani et al

TAXUS IV

E-SIRIUS

Study ID

DIABETES

PRISON II

STRATEGY

RAVEL

SES-SMART

TAXUS V

Typhoon

MISSION!

SCORPIUSSESAMI

D+L Overall

Passion

C-SIRIUS

Pache et al

SIRIUS

0.97 (0.81, 1.15)

0.82 (0.37, 1.84)

1.61 (0.57, 4.53)

2.00 (0.63, 6.38)1.35 (0.23, 7.78)

2.00 (0.19, 21.38)

0.89 (0.63, 1.25)

1.08 (0.25, 2.24)

ES (95% CI)

1.44 (0.48, 4.33)

0.50 (0.09, 2.67)

0.84 (0.36, 1.96)

1.75 (0.73, 4.16)

0.21 (0.02, 1.71)

0.97 (0.57, 1.65)

1.01 (0.38, 2.65)

0.48 (0.09, 2.59)

1.28 (0.35, 4.61)0.43 (0.11, 1.63)

0.97 (0.81, 1.15)

0.70 (0.36, 1.36)

0.68 (0.11, 4.04)

1.40 (0.45, 4.35)

1.02 (0.67, 1.54)

100.00

4.80

2.87

2.301.00

0.55

26.29

2.57

(I-V)

2.55

1.07

4.30

4.08

0.62

10.92

3.27

1.09

Weight

1.861.70

6.99

0.95

2.40

17.82

%

0.97 (0.81, 1.15)

0.82 (0.37, 1.84)

1.61 (0.57, 4.53)

2.00 (0.63, 6.38)1.35 (0.23, 7.78)

2.00 (0.19, 21.38)

0.89 (0.63, 1.25)

1.08 (0.25, 2.24)

ES (95% CI)

1.44 (0.48, 4.33)

0.50 (0.09, 2.67)

0.84 (0.36, 1.96)

1.75 (0.73, 4.16)

0.21 (0.02, 1.71)

0.97 (0.57, 1.65)

1.01 (0.38, 2.65)

0.48 (0.09, 2.59)

1.28 (0.35, 4.61)0.43 (0.11, 1.63)

0.97 (0.81, 1.15)

0.70 (0.36, 1.36)

0.68 (0.11, 4.04)

1.40 (0.45, 4.35)

1.02 (0.67, 1.54)

100.00

4.80

2.87

2.301.00

0.55

26.29

2.57

(I-V)

2.55

1.07

4.30

4.08

0.62

10.92

3.27

1.09

Weight

1.861.70

6.99

0.95

2.40

17.82

%

1.1 1 10

8,867 patients, 21 trials8,867 patients, 21 trials

Favors BMS

Estimate (95% CI) Weight (%)

0.97 (0.81,1.15)0.97 (0.81,1.15), p=0.72

Random Effects*Fixed Effects (I2=0.0%)

Favors DES

Mean f/u 2.9 yrs

Ajay J. Kirtane and Gregg W. Stone, 2008

All-Cause Mortality: RCTs (On-Label)All-Cause Mortality: RCTs (On-Label)


Ortolani et al

TAXUS V - Simple

D+L Overall

TAXUS IV

Pache et al

C-SIRIUS

E-SIRIUS

SIRIUS

TAXUS II

Study ID

RAVEL

SCORPIUS

1.05 (0.84, 1.30)

2.00 (0.19, 21.38)

1.09 (0.53, 2.22)

1.05 (0.84, 1.30)

0.89 (0.63, 1.25)

1.40 (0.45, 4.35)

0.68 (0.11, 4.04)

1.08 (0.25, 2.24)

1.02 (0.67, 1.54)

1.61 (0.57, 4.53)

ES (95% CI)

1.75 (0.73, 4.16)

1.28 (0.35, 4.61)

100.00

0.85

9.20

40.20

3.67

%

1.45

3.93

27.25

4.39

(I-V)

6.23

2.84

Weight

1.1 1 10


Favors DES Favors BMS


1.05 (0.84,1.30)

1.05 (0.84,1.30), p=0.69

Random Effects

*Fixed Effects (I2=0.0%)

Mean f/u 4.0 yrs


All-Cause Mortality: RCT’s (Off-Label)All-Cause Mortality: RCT’s (Off-Label)


HAAMU-STENT

Passion

PRISON II

MISSION!

DIABETES

BASKET (SES only)

Seville

D+L Overall

SES-SMART

STRATEGY

TAXUS V - complex

Study ID

SESAMI

Typhoon

0.84 (0.62, 1.13)

2.00 (0.63, 6.38)

0.70 (0.36, 1.36)

0.50 (0.09, 2.67)

0.48 (0.09, 2.59)

1.44 (0.48, 4.33)

0.82 (0.37, 1.84)

1.35 (0.23, 7.78)

0.84 (0.62, 1.13)

0.21 (0.02, 1.71)

0.84 (0.36, 1.96)

0.84 (0.38, 1.84)

ES (95% CI)

0.43 (0.11, 1.63)

1.01 (0.38, 2.65)

100.00

6.64

20.16

Weight

3.10

3.16

7.36

13.84

%

2.87

1.80

12.40

14.32

(I-V)

4.90

9.44

1.1 1 10




0.84 (0.62,1.13)

0.84 (0.62,1.13), p=0.24

Random Effects


Mean f/u 1.5 yrs


All-Cause Mortality: All RegistriesAll-Cause Mortality: All Registries

NOTE: Weights are from random effects analysis

D+L Overall (I-squared = 70.1%, p = 0.000)

Ontario (matched)Germany Metabolic Syndrome

GHOST (adjusted)

RESTEMARTS II (from RCT)

ACUITY (from RCT)

Western Denmark (adjusted)

STENT (adjusted)Massachusetts (matched)

Cedars Acute MI

I-V Overall

NHLBI (on label, adjusted)

Wake Forest (adjusted)

DEScover (unadjusted)

Multicenter SVG (adjusted)

MIDAS (adjusted)

Liverpool (matched)

ERACI III (from RCT)

SCAAR (adjusted)Asan Korea (adjusted)

Study ID

Melbourne

McMaster STEMI (adjusted)

REAL (adjusted)

Mayo FFR SubstudyItalian Diabetic Multivessel (adjusted)

Washington Hosp Center (matched)Rotterdam Off-Label

NHLBI (off label, adjusted)

NY State (adjusted, unmatched)

0.80 (0.72, 0.88)

0.71 (0.59, 0.84) 1.47 (0.65, 3.35)

0.55 (0.36, 0.83)

0.73 (0.51, 1.05) 0.74 (0.41, 1.35)

0.63 (0.49, 0.82)

1.00 (0.86, 1.17)

0.69 (0.55, 0.87) 0.79 (0.71, 0.89)

0.82 (0.37, 1.83)

0.83 (0.79, 0.86)

1.47 (0.87, 2.48)

0.72 (0.55, 0.95)

0.53 (0.35, 0.80)

1.33 (0.47, 3.76)

0.66 (0.59, 0.74)

0.45 (0.24, 0.84)

1.18 (0.54, 2.58)

1.03 (0.94, 1.14) 0.60 (0.46, 0.79)

ES (95% CI)

0.67 (0.23, 1.94)

0.17 (0.03, 0.97)

0.83 (0.70, 0.98)

1.00 (0.21, 4.75) 1.22 (0.36, 4.10)

1.16 (0.78, 1.75) 0.98 (0.85, 1.13)

0.94 (0.64, 1.38)

0.84 (0.72, 0.97)

100.00

5.981.15

3.09

3.631.92

Weight

4.87

6.29

5.256.80

1.20

2.31

4.66

3.13

0.76

6.80

1.78

%

1.25

6.984.70

(D+L)

0.73

0.29

6.10

0.360.57

3.216.44

3.40

6.35

1.1 1 10

161,232 patients, 28 registries161,232 patients, 28 registries

Favors BMS


0.80 (0.72,0.88), p<0.0010.83 (0.79,0.86)

Favors DES

*Random Effects (I2=70.1%)Fixed Effects

Mean f/u 2.5 yrs


MI: All RCTsMI: All RCTs8,850 patients, 20 trials8,850 patients, 20 trials

D+L Overall (I-squared = 3.0%, p = 0.420)I-V Overall

SCORPIUS

TAXUS II

PRISON II

TAXUS V

Passion

STRATEGY

MISSION!

Typhoon

SIRIUS

TAXUS IV

BASKET (All)

RAVEL

Ortolani et alDIABETES

HAAMU-STENT

Study ID

E-SIRIUS

SES-SMART

SCANDSTENT

SESAMI

C-SIRIUS

1.1 1 10


SESAMI

Passion

C-SIRIUS

RAVEL

TAXUS IV

TAXUS V

SCORPIUS

SIRIUS

DIABETES

MISSION!

E-SIRIUS

SCANDSTENT

Study ID

Ortolani et al

SES-SMARTSTRATEGY

HAAMU-STENT

BASKET (All)

Typhoon

TAXUS II

PRISON II

D+L Overall

0.94 (0.79, 1.13)

1.00 (0.20, 4.88)

0.83 (0.26, 2.69)

0.59 (0.14, 2.47)

1.24 (0.49, 3.14)

0.99 (0.66, 1.48)

1.27 (0.79, 2.04)

0.82 (0.23, 2.95)

0.96 (0.59, 1.55)

0.60 (0.20, 1.50)

0.62 (0.28, 1.39)

1.94 (0.93, 4.02)

0.33 (0.09, 1.18)

ES (95% CI)

1.50 (0.26, 8.61)

0.16 (0.04, 0.67)0.82 (0.31, 2.40)

0.25 (0.03, 2.19)

1.15 (0.64, 2.08)

0.80 (0.22, 2.97)

0.63 (0.23, 1.72)

0.83 (0.26, 2.64)

0.94 (0.78, 1.13)

100.00

1.29

2.40

1.59

3.80

20.13

Weight

14.59

2.02

14.07

3.23

5.11

6.13

%

1.98

(I-V)

1.07

1.653.13

0.71

9.45

1.94

3.24

2.44

1.1 1 10


0.94 (0.78,1.13)0.94 (0.79,1.13), p=0.54


Random Effects*Fixed Effects (I2=3.0%)


Mean f/u 2.9 yrs

MI: RCTs (On Label)MI: RCTs (On Label)


RAVEL

Study ID

D+L Overall

SIRIUS

E-SIRIUS

TAXUS II

TAXUS IV

C-SIRIUS

TAXUS V - Simple

SCORPIUS

Ortolani et al

1.03 (0.81, 1.30)

1.24 (0.49, 3.14)

ES (95% CI)

1.03 (0.81, 1.30)

0.96 (0.59, 1.55)

1.94 (0.93, 4.02)

0.63 (0.23, 1.72)

0.99 (0.66, 1.48)

0.59 (0.14, 2.47)

0.98 (0.52, 1.81)

0.82 (0.23, 2.95)

1.50 (0.26, 8.61)

100.00

6.29

(I-V)

23.26

%

10.13

5.36

33.28

2.63

13.95

Weight

3.33

1.77

1.1 1 10




1.03 (0.81,1.30)

1.03 (0.81,1.30), p=0.82

Random Effects



Mean f/u 4.4 yrs

MI: RCT’s (Off Label)MI: RCT’s (Off Label)4,532 patients, 12 trials4,532 patients, 12 trials

1.1 1 10


SCANDSTENT

HAAMU-STENT

Typhoon

D+L Overall

SES-SMART

PRISON II

TAXUS V - complex

Passion

Study ID

STRATEGY

MISSION!

SESAMI

BASKET (All)

DIABETES

0.83 (0.62, 1.10)

0.33 (0.09, 1.18)

0.25 (0.03, 2.19)

0.80 (0.22, 2.97)

0.77 (0.54, 1.10)

0.16 (0.04, 0.67)

0.83 (0.26, 2.64)

1.84 (0.86, 3.94)

0.83 (0.26, 2.69)

ES (95% CI)

0.82 (0.31, 2.40)

0.62 (0.28, 1.39)

1.00 (0.20, 4.88)

1.15 (0.64, 2.08)

0.60 (0.20, 1.50)

100.00

5.08

1.83

4.97

4.24

Weight

6.26

%

14.52

6.16

(I-V)

8.03

13.11

3.30

24.22

8.29

1.1 1 10



SCANDSTENT

HAAMU-STENT

Typhoon

D+L Overall

SES-SMART

PRISON II

TAXUS V - complex

Passion

Study ID

STRATEGY

MISSION!

SESAMI

BASKET (All)

DIABETES

0.83 (0.62, 1.10)

0.33 (0.09, 1.18)

0.25 (0.03, 2.19)

0.80 (0.22, 2.97)

0.77 (0.54, 1.10)

0.16 (0.04, 0.67)

0.83 (0.26, 2.64)

1.84 (0.86, 3.94)

0.83 (0.26, 2.69)

ES (95% CI)

0.82 (0.31, 2.40)

0.62 (0.28, 1.39)

1.00 (0.20, 4.88)

1.15 (0.64, 2.08)

0.60 (0.20, 1.50)

100.00

5.08

1.83

4.97

4.24

Weight

6.26

%

14.52

6.16

(I-V)

8.03

13.11

3.30

24.22

8.29

1.1 1 10


0.77 (0.54,1.10)

0.83 (0.62,1.10), p=0.19

Random Effects



Mean f/u 1.5 yrs

MI: All RegistriesMI: All Registries



ACUITY (from RCT)

Melbourne

ARTS II (from RCT)

Asan Korea (adjusted)

Ontario (matched)

Study ID

NHLBI (on label, adjusted)

Washington Hosp Center (matched)

STENT (adjusted)



Germany Metabolic Syndrome

NHLBI (off label, adjusted)

Western Denmark (adjusted)

GHOST (adjusted)

SCAAR (adjusted)

REAL (adjusted)

RESTEM

DEScover (unadjusted)

Brazil Large Vessels

Cedars Acute MI

Massachusetts (matched)

Italian Diabetic Multivessel (adjusted)

I-V Overall

Mayo FFR Substudy


0.89 (0.80, 0.98)

1.07 (0.91, 1.25)

1.00 (0.39, 2.58)

0.53 (0.32, 0.88)

0.66 (0.42, 1.05)

1.10 (0.91, 1.32)

ES (95% CI)

0.71 (0.47, 1.05)

0.51 (0.29, 0.88)

0.69 (0.52, 0.92)

2.30 (0.91, 5.96)

0.84 (0.60, 1.18)

0.23 (0.07, 0.78)

0.71 (0.50, 1.00)

1.29 (1.06, 1.57)

1.12 (0.74, 1.70)

1.01 (0.91, 1.11)

0.92 (0.76, 1.11)

0.80 (0.52, 1.23)

0.69 (0.40, 1.18)

1.50 (0.25, 8.90)

0.25 (0.06, 1.16)

0.92 (0.83, 1.02)

1.02 (0.46, 2.25)

0.96 (0.91, 1.01)

0.67 (0.12, 3.84)

0.28 (0.04, 1.71)

100.00

8.90

1.10

3.09

3.55

8.26

(D+L)

4.21

2.69

6.10

1.11

5.15

0.70

5.01

Weight

%

8.02

4.03

10.17

8.18

3.86

2.80

0.33

0.48

10.10

1.50

0.35

0.30

0.89 (0.80, 0.98)

1.07 (0.91, 1.25)

1.00 (0.39, 2.58)

0.53 (0.32, 0.88)

0.66 (0.42, 1.05)

1.10 (0.91, 1.32)

ES (95% CI)

0.71 (0.47, 1.05)

0.51 (0.29, 0.88)

0.69 (0.52, 0.92)

2.30 (0.91, 5.96)

0.84 (0.60, 1.18)

0.23 (0.07, 0.78)

0.71 (0.50, 1.00)

1.29 (1.06, 1.57)

1.12 (0.74, 1.70)

1.01 (0.91, 1.11)

0.92 (0.76, 1.11)

0.80 (0.52, 1.23)

0.69 (0.40, 1.18)

1.50 (0.25, 8.90)

0.25 (0.06, 1.16)

0.92 (0.83, 1.02)

1.02 (0.46, 2.25)

0.96 (0.91, 1.01)

0.67 (0.12, 3.84)

0.28 (0.04, 1.71)

100.00

8.90

1.10

3.09

3.55

8.26

(D+L)

4.21

2.69

6.10

1.11

5.15

0.70

5.01

Weight

%

8.02

4.03

10.17

8.18

3.86

2.80

0.33

0.48

10.10

1.50

0.35

0.30

1.1 1 10




0.89 (0.80,0.98), p=0.023 0.96 (0.91,1.01)


*MI is QWMI in Washington Hospital Center, RESTEM

Ajay J. Kirtane and Gregg W. Stone, 2008Mean f/u 2.5 yrs

TVR: All RCTsTVR: All RCTs



Pache et al

Study ID

HAAMU-STENT

C-SIRIUS

Typhoon

STRATEGY

SIRIUS

SCANDSTENT

TAXUS II

PRISON II

TAXUS IV

E-SIRIUS

MISSION!

Ortolani et al

SESAMI

I-V Overall

TAXUS V

RAVEL

0.45 (0.37, 0.54)

0.38 (0.23, 0.64)

ES (95% CI)

0.33 (0.09, 1.19)

0.30 (0.10, 0.93)

0.42 (0.25, 0.69)

0.34 (0.16, 0.77)

0.48 (0.37, 0.62)

0.17 (0.09, 0.33)

0.61 (0.35, 1.08)

0.37 (0.19, 0.69)

0.57 (0.45, 0.72)

0.35 (0.21, 0.56)

0.38 (0.17, 0.85)

0.58 (0.25, 1.36)

0.36 (0.17, 0.79)

0.51 (0.45, 0.57)

0.77 (0.60, 0.98)

0.51 (0.25, 1.04)

100.00

7.14

(D+L)

1.91

2.45

7.20

4.22

11.51

5.44

%

6.44

5.49

11.94

Weight

7.45

4.08

3.78

4.36

11.75

4.83

1.1 1 10



Estimate (95% CI)Weight (%)

0.45 (0.37,0.54), p<0.0010.51 (0.45,0.57)


Mean f/u 3.2 yrsAjay J. Kirtane and Gregg W. Stone, 2008

TVR: RCTs (On Label)TVR: RCTs (On Label)



E-SIRIUS

TAXUS IV

SIRIUS

RAVEL

I-V Overall

TAXUS II

Study ID

C-SIRIUS

TAXUS V - Simple

Ortolani et al

Pache et al

0.53 (0.43, 0.65)

0.35 (0.21, 0.56)

0.57 (0.45, 0.72)

0.48 (0.37, 0.62)

0.51 (0.25, 1.04)

0.54 (0.47, 0.62)

0.61 (0.35, 1.08)

ES (95% CI)

0.30 (0.10, 0.93)

0.91 (0.64, 1.29)

0.58 (0.25, 1.36)

0.38 (0.23, 0.64)

100.00

10.98

19.99

19.03

6.65

9.25

(D+L)

3.19

15.38

5.08

Weight

10.44

%

1.1 1 10




0.53 (0.43,0.65), p<0.001

0.54 (0.47,0.62)

*Random Effects (I2=48.8%)

Fixed Effects

Mean f/u 4.2 yrs


TVR: RCTs (Off Label)TVR: RCTs (Off Label)



Typhoon

Study ID

STRATEGY

SCANDSTENT

TAXUS V - complex

I-V Overall

HAAMU-STENT

SESAMI

MISSION!

PRISON II

0.38 (0.27, 0.52)

0.42 (0.25, 0.69)

ES (95% CI)

0.34 (0.16, 0.77)

0.17 (0.09, 0.33)

0.62 (0.44, 0.86)

0.42 (0.34, 0.52)

0.33 (0.09, 1.19)

0.36 (0.17, 0.79)

0.38 (0.17, 0.85)

0.37 (0.19, 0.69)

100.00

16.43

(D+L)

10.35

12.95

21.55

%

4.98

10.65

10.04

Weight

13.06

1.1 1 10




0.38 (0.27,0.52), p<0.001

0.42 (0.34,0.52)

*Random Effects (I2=47.8%)

Fixed Effects

Mean f/u 1.6 yrs


TVR: All RegistriesTVR: All Registries



DEScover (adjusted)



GHOST (adjusted)

Montevergine

STENT (adjusted)

Washington Hosp Center (matched)

I-V Overall

Asan Korea (adjusted)

NY State (adjusted, unmatched)

RESTEM

Ontario (matched)

Cedars Acute MI

Brazil Large Vessels

REAL (adjusted)

Multicenter SVG (adjusted)

Study ID

Mayo FFR Substudy


0.53 (0.47, 0.61)

0.58 (0.40, 0.83)

0.32 (0.05, 1.92)

0.63 (0.48, 0.83)

0.28 (0.20, 0.39)

0.51 (0.39, 0.68)

0.58 (0.47, 0.71)

0.65 (0.49, 0.85)

0.57 (0.54, 0.60)

0.32 (0.24, 0.43)

0.54 (0.50, 0.60)

0.62 (0.47, 0.80)

0.69 (0.60, 0.80)

0.22 (0.08, 0.62)

0.43 (0.17, 1.10)

0.67 (0.59, 0.76)

0.58 (0.28, 1.18)

ES (95% CI)

0.18 (0.04, 0.78)

0.58 (0.39, 0.86)

100.00

5.81

0.46

7.38

6.31

7.30

8.70

7.35

Weight

7.05

10.70

7.53

9.88

1.34

1.57

10.17

2.41

(D+L)

0.68

5.35

%

1.1 1 10



Estimate (95% CI)Weight (%)

0.53 (0.47,0.61), p<0.001 0.57 (0.54,0.60)


Mean f/u 2.2 yrs


Summary: DES vs. BMSSummary: DES vs. BMS Treatment Effect EstimatesTreatment Effect Estimates

MortalityMortality MIMI TVRTVR

RCTsRCTs 8,867 pts, 8,867 pts, 21 trials 21 trials

8,850 pts, 8,850 pts, 20 trials 20 trials

7,291 pts, 7,291 pts, 16 trials 16 trials

- Fixed effectsFixed effects- Random effectsRandom effects

0.970.970.970.97

0.940.940.940.94

0.510.510.450.45

RegistriesRegistries 161,232 pts, 161,232 pts, 28 studies 28 studies

129,955 pts, 129,955 pts, 24 studies 24 studies

73,819 pts, 73,819 pts, 17 studies 17 studies

- Fixed effectsFixed effects- Random effectsRandom effects

0.830.830.800.80

0.960.960.890.89

0.570.570.530.53

<1.0 <1.0 DES better DES better

Conclusions (1)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

Conclusions (2)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”

Documents

Comprehensive Meta-Analysis of DES vs. BMS Randomized Trials and Registries