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BackgroundBackground

• There is ongoing debate to identify the most effective There is ongoing debate to identify the most effective

drug-eluting stent between the two currently most used drug-eluting stent between the two currently most used

devices (ie, sirolimus- [SES] and paclitaxel-eluting devices (ie, sirolimus- [SES] and paclitaxel-eluting

stents [PES])stents [PES])

• In order to overcome the limitations and apparently In order to overcome the limitations and apparently

conflicting results of single randomized trials, directconflicting results of single randomized trials, direct11

and indirectand indirect22 comparison meta-analyses have been comparison meta-analyses have been

performedperformed

• Most recently, methods have been developed to Most recently, methods have been developed to

combine direct and indirect meta-analyses,combine direct and indirect meta-analyses,33 but to date but to date

they have been employed rarelythey have been employed rarely

1Kastrati et al, JAMA 2005; 2Biondi-Zoccai et al, Int J Cardiol 2005; 3Bucher et al, J Clin Epidemiol 1997

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RationaleRationale

1Bucher et al, J Clin Epidemiol 1997; 2Song et al, BMJ 2003; 3Psaty et al, JAMA 2003

TREATMENT TREATMENT AA

TREATMENT TREATMENT BB

Direct comparisonDirect comparison

TREATMENT TREATMENT AA

TREATMENT TREATMENT BBIndirect comparisonIndirect comparison

TREATMENT TREATMENT CC

TREATMENT TREATMENT CC

Direct and indirect comparison meta-analyses can beDirect and indirect comparison meta-analyses can be

then combined using a generic inverse variance approachthen combined using a generic inverse variance approach1-31-3

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Aim of the studyAim of the study

• We aimed to search, appraise and then combine We aimed to search, appraise and then combine

previously published direct and indirect previously published direct and indirect

comparison meta-analyses of SES vs PEScomparison meta-analyses of SES vs PES

• The goal was to maximize statistical precision The goal was to maximize statistical precision

and power, as well as increasing robustness and and power, as well as increasing robustness and

validity of such SES vs PES comparisonvalidity of such SES vs PES comparison1-31-3

1Bucher et al, J Clin Epidemiol 1997; 2Song et al, BMJ 2003; 3Psaty et al, JAMA 2003

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MethodsMethods• Direct and indirect comparison meta-analyses of Direct and indirect comparison meta-analyses of

SES vs PES were systematically searched in SES vs PES were systematically searched in electronic databaseselectronic databases

• Pertinent results for binary angiographic restenosis Pertinent results for binary angiographic restenosis and target lesion revascularization at 6-12 and target lesion revascularization at 6-12 months were abstracted and pooled by means of months were abstracted and pooled by means of fixed effects generic inverse variance weightingfixed effects generic inverse variance weighting

• We then computed odds ratios (OR) with 95% We then computed odds ratios (OR) with 95% confidence intervals, and inconsistency (Iconfidence intervals, and inconsistency (I22) as a ) as a measure of statistical heterogeneitymeasure of statistical heterogeneity

• Two-tailed statistical significance was set at the Two-tailed statistical significance was set at the 0.05 level0.05 level

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ResultsResults• We identified a full report of direct comparison We identified a full report of direct comparison

meta-analysis,meta-analysis,11 which pooled 6 head-to-head which pooled 6 head-to-head randomized clinical trials comparing SES vs PES randomized clinical trials comparing SES vs PES in 3669 patients (1845 treated with SES and 1824 in 3669 patients (1845 treated with SES and 1824 with PES)with PES)

• We also retrieved an indirect comparison meta-We also retrieved an indirect comparison meta-analysis,analysis,22 which compared SES vs PES from 9 which compared SES vs PES from 9 additional trials enrolling 2185 patients (1007 additional trials enrolling 2185 patients (1007 treated with SES and 1178 treated with PES), treated with SES and 1178 treated with PES), using as benchmark the bare-metal-stent control using as benchmark the bare-metal-stent control group for each studygroup for each study

1Kastrati et al, JAMA 2005; 2Biondi-Zoccai et al, Int J Cardiol 2005

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ResultsResultsTrialTrial SES PtsSES Pts PES PtsPES Pts BMS PtsBMS PtsCORPAL

ISAR-DESIRE

ISAR-DIABETES

REALITY

SIRTAX

TAXI

C-SIRIUS

E-SIRIUS

RAVEL

SES-SMART

SIRIUS

TAXUS I

TAXUS II MR

TAXUS II SR

TAXUS IV

TAXUS VI

331

100

125

684

503

102

50

175

120

129

533

-

-

-

-

-

321

100

125

669

509

100

-

-

-

-

-

31

135

131

662

219

-

-

-

-

-

-

50

178

118

128

525

30

134

136

652

227

DIR

EC

TD

IREC

T

META

-AN

ALY

SIS

META

-AN

ALY

SIS

IND

IREC

TIN

DIR

EC

T

META

-AN

ALY

SIS

META

-AN

ALY

SIS

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ResultsResults

• Pooling these two systematic reviews, by Pooling these two systematic reviews, by means of a fixed effects generic inverse means of a fixed effects generic inverse variance method lead to the inclusion of a variance method lead to the inclusion of a total of 5854 patients (2852 treated with SES total of 5854 patients (2852 treated with SES and 3002 with PES)and 3002 with PES)

• In this population the use of SES in In this population the use of SES in comparison to PES was associated with comparison to PES was associated with significant reductions in binary angiographic significant reductions in binary angiographic restenosis (p<0.0001) and target lesion restenosis (p<0.0001) and target lesion revascularization (p=0.0008), even if the revascularization (p=0.0008), even if the former end-point was statistically former end-point was statistically inhomogeneousinhomogeneous

1Kastrati et al, JAMA 2005; 2Biondi-Zoccai et al, Int J Cardiol 2005

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Binary angiographic restenosisBinary angiographic restenosis

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Target lesion revascularizationTarget lesion revascularization

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ConclusionsConclusions

• This review combining previous direct and This review combining previous direct and indirect meta-analyses of SES vs PES indirect meta-analyses of SES vs PES definitively establish the superiority of SES definitively establish the superiority of SES in comparison to PES in patients undergoing in comparison to PES in patients undergoing percutaneous coronary interventionpercutaneous coronary intervention

• These data, notwithstanding their inherent These data, notwithstanding their inherent limitations, should be taken into account limitations, should be taken into account together with costs in clinical decision together with costs in clinical decision makingmaking

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