why are drug-eluting stents safer than bare-metal stents?
DESCRIPTION
Why are drug-eluting stents safer than bare-metal stents?. Giuseppe Biondi Zoccai, MD Sapienza University of Rome , Rome , Italy METCARDIO, Ospedaletti , Italy [email protected]. 10 th International Cardiology Congress – Patras – 4-6 May 2012. LEARNING GOALS. - PowerPoint PPT PresentationTRANSCRIPT
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Why are drug-eluting Why are drug-eluting stents safer than stents safer than
bare-metal stents?bare-metal stents?Giuseppe Biondi Zoccai, MDGiuseppe Biondi Zoccai, MD
Sapienza University of Rome, Rome, ItalySapienza University of Rome, Rome, ItalyMETCARDIO, Ospedaletti, ItalyMETCARDIO, Ospedaletti, Italy
[email protected]@uniroma1.it
10th International Cardiology Congress – Patras – 4-6 May 2012
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LEARNING GOALS• Current paradigm
• Why could drug-eluting stents possibly be safer than bare-metal stents?
• The case for network meta-analyses
• Stent thrombosis with drug-eluting versus bare-metal stents: evidence from a network meta-analysis
• Paradigm shift
www.metcardio.org
LEARNING GOALS• Current paradigm
• Why could drug-eluting stents possibly be safer than bare-metal stents?
• The case for network meta-analyses
• Stent thrombosis with drug-eluting versus bare-metal stents: evidence from a network meta-analysis
• Paradigm shift
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WHAT IS STENT THROMBOSIS?
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total acute subacute late very late
INCIDENCE OF STENT THROMBOSIS*
*at a median folllow-up of 18 months
D’Ascenzo et al, Int J Cardiol 2012
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PREDICTORS OF STENT THROMBOSIS*
*number of studies confirming the independent role of the predictor
D’Ascenzo et al, Int J Cardiol 2012
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IMPACT OF STENT THROMBOSIS
Chechi et al, J Am Coll Cardiol 2008
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2006: ANNUS HORRIBILIS FOR DRUG-ELUTING STENTS
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Nordmann et al, Eur Heart J 2006
Camenzind, ESC/WCC 2006
Bavry et al, Am J Med 2006
2006: ANNUS HORRIBILIS FOR DRUG-ELUTING STENTS
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LEARNING GOALS• Current paradigm
• Why could drug-eluting stents possibly be safer than bare-metal stents?
• The case for network meta-analyses
• Stent thrombosis with drug-eluting versus bare-metal stents: evidence from a network meta-analysis
• Paradigm shift
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POTENTIAL OF EVEROLIMUS-ELUTING STENTS
Verheye et al, J Am Coll Cardiol 2007
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POTENTIAL OF EVEROLIMUS-ELUTING STENTS
Kolandaivelu et al, Circulation 2011
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RISK OF STENT THROMBOSIS WITH EVEROLIMUS-ELUTING VERSUS
BARE-METAL STENTS
Sabate, ESC 2011Kaiser et al, New Engl J Med 2010
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POTENTIAL OF ZOTAROIMUS-ELUTING STENTS
Guagliumi et al, J Am Coll Cardiol Intv 2010
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LEARNING GOALS• Current paradigm
• Why could drug-eluting stents possibly be safer than bare-metal stents?
• The case for network meta-analyses
• Stent thrombosis with drug-eluting versus bare-metal stents: evidence from a network meta-analysis
• Paradigm shift
www.metcardio.org
META-ANALYSES“I like to think of the meta-analytic process as similar to being in a helicopter.
On the ground individual trees are visible with high resolution.
This resolution diminishes as the helicopter rises, and in its place we begin to see patterns not visible from the ground.”
Ingram Olkin
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SYSTEMATIC REVIEW AND META-ANALYSES
• What is a systematic review?
– A systematic appraisal of the methodological quality,
clinical relevance and consistency of published
evidence on a specific clinical topic in order to provide
clear suggestions for a specific healthcare problem
• What is a meta-analysis?
– A quantitative synthesis that, preserving the identity of
individual studies, tries to provide an estimate of the
overall effect of an intervention, exposure, or diagnostic
strategy
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ARGUABLY THE MOST IMPORTANT META-ANALYSIS EVER….
Antman et al, JAMA 1992
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…SHOWING DISCREPANCIES AMONG EVIDENCE AND EXPERTS
www.metcardio.orgHsia et al, Ann Surg 2008
P for effect
Inconsistency
P for heterogeneity
STANDARD (PAIR-WISE) META-ANALYSESPoint estimate
95% confidence interval
Summary estimate
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INDIRECT AND NETWORKMETA-ANALYSES
Biondi-Zoccai et al, HSR Proceedings 2011
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PARALLEL HIERARCHY OF CLINICAL RESEARCH
Biondi-Zoccai et al, HSR Proceedings 2011
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LEARNING GOALS• Current paradigm
• Why could drug-eluting stents possibly be safer than bare-metal stents?
• The case for network meta-analyses
• Stent thrombosis with drug-eluting versus bare-metal stents: evidence from a network meta-analysis
• Paradigm shift
www.metcardio.org
NETWORK META-ANALYSIS OF STENT THROMBOSIS
Palmerini, Biondi-Zoccai et al, Lancet 2012
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GOAL• We aimed to perform direct, indirect and
combined (i.e. network) meta-analyses of the risk of stent thrombosis with all FDA approved coronary stents:– Bare-metal stents (BMS); Cobalt-chromium
everolimus-eluting stents (CoCr-EES); Endeavor zotarolimus-eluting stents (End-ZES); Paclitaxel-eluting stents (PES); Platinum-chromium everolimus-eluting stents (PtCr-EES); Resolute zotarolimus-eluting stents (Res-ZES); Sirolimus-eluting stents (SES)
Palmerini, Biondi-Zoccai et al, Lancet 2012
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SEARCH AND SELECTION
• Randomized trials of FDA approved coronary stents reporting on stent thrombosis according to the Academic Research Consortium (ARC) definitions were searched in multiple databases (including MEDLINE/PubMed).
• Authors and experts were queried for additional data and insights on other potentially pertinent studies.
Palmerini, Biondi-Zoccai et al, Lancet 2012
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END-POINTS• Primary end-point:
– 1-year definite stent thrombosis
• Secondary end-points:– Definite stent thrombosis occurring before 30 days,
after 30 days, and within 2 years– Definite or probable stent thrombosis (at the above
time points) – Death, cardiac death and myocardial infarction
within 2 years
Palmerini, Biondi-Zoccai et al, Lancet 2012
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ANALYSIS
• Direct (pair-wise) meta-analyses were performed with a random-effect method computing odds ratios (OR) with 95% confidence intervals (95%CI).
• Indirect and network meta-analyses were performed with a random-effect method within a Bayesian hierarchical framework, also computing OR and 95%CI.
Palmerini, Biondi-Zoccai et al, Lancet 2012
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ANALYSIS• Small study effects were appraised by funnel
plot inspection.• Statistical consistency in pair-wise and network
analyses was appraised with I2.• Sensitivity analyses were conducted using a
fixed-effect method and restricted to several subgroups of interest.
• RevMan and WinBUGS were used for computations.
Palmerini, Biondi-Zoccai et al, Lancet 2012
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REVIEW PROFILE
FDAapproved
stents(BMS, SES, PES, End-ZES, Res-ZES, CoCr-EES, PtCr-EES)
49 RCTs
50,844 pts
2602 potentially relevant articles
2441 excluded2117 not a comparison of DES324 post-hoc, subgroup, follow-up, or pooled analyses
Review of titleand abstract
161 articles needing full review
112 excluded84 not an RCT13 DES not FDA approved11 no ARC definition4 DES pooled
Full-textreview
49 RCTs meeting criteria
Palmerini, Biondi-Zoccai et al, Lancet 2012
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EVIDENCE NETWORK9 studies9 studies
PESPESBMSBMS
SESSESEnd-ZESEnd-ZES
Res-ZESRes-ZES PtCr-EESPtCr-EES
CoCr-EESCoCr-EES
1 study
1 study
8 studies
8 studies1 st
udy
1 st
udy
4 studies
4 studies 9 studies
9 studies
6 studies6 studies
6 studies6 studies
2 st
udies
2 st
udies
2 studies
2 studies 5 st
udie
s
5 st
udie
s
Palmerini, Biondi-Zoccai et al, Lancet 2012
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1-YEAR DEFINITE STENT THROMBOSIS
Palmerini, Biondi-Zoccai et al, Lancet 2012
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30-DAY DEFINITE STENT THROMBOSIS
Odds Ratio [95%]
CoCr-EES vs BMS
CoCr-EES vs PES
CoCr-EES vs SES
CoCr-EES vs End-ZES
CoCr-EES vs Res-ZES
PtCr-EES vs BMS
PtCr-EES vs PES
PtCr-EES vs End-ZES
PtCr-EES vs Res-ZES
SES vs BMS
0.21 (0.11-0.42)
0.27 (0.14-0.51)
0.40 (0.21-0.79)
0.22 (0.09-0.54)
0.07 (0.00-0.46)
0.06 (0.00-0.68)
0.07 (0.00-0.83)
0.06 (0.00-0.73)
0.02 (0.00-0.43)
0.54 (0.30-0.90)
Favors Stent 1
1010.10.01
Favors Stent 2
Palmerini, Biondi-Zoccai et al, Lancet 2012
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30-DAY TO 1-YEAR DEFINITE STENT THROMBOSIS
Odds Ratio[95%]
CoCr-EES vs BMS
CoCr-EES vs PES
CoCr-EES vs End-ZES
End-ZES vs SES
0.27 (0.08-0.74)
0.24 (0.08-0.62)
0.13 (0.02-0.56)
4.06 (1.11-18.5)
Favors Stent 1
1001010.10.01
Favors Stent 2
Palmerini, Biondi-Zoccai et al, Lancet 2012
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2-YEAR DEFINITE STENT THROMBOSIS
Odds Ratio [95%]
CoCr-EES vs BMS
CoCr-EES vs PES
0.35 (0.17-0.69)
0.34 (0.19-0.62)
Favors Stent 1
1010.10.01
Favors Stent 2
Palmerini, Biondi-Zoccai et al, Lancet 2012
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OTHER RESULTS FOR DEFINITE STENT THROMBOSIS
Palmerini, Biondi-Zoccai et al, Lancet 2012
www.metcardio.orgPalmerini, Biondi-Zoccai et al, Lancet 2012
OTHER RESULTS FOR DEFINITE STENT THROMBOSIS
www.metcardio.orgPalmerini, Biondi-Zoccai et al, Lancet 2012
OTHER RESULTS FOR DEFINITE OR PROBABLE STENT THROMBOSIS
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STATISTICAL CONSISTENCY
IV = inverse varianceIV = inverse varianceSE = standard errorSE = standard error
Odds Ratio IVRandom, 95% CI
1010.10.001
Favors CoCr-EESFavors BMS
WeightSELog (odds ratio)
Definite stent thrombosisDirect estimateIndirect estimateTotal (95% CI)Test for overall effect Z=4.82 (p<0.00001)
Definite or probable thrombosisDirect estimateIndirect estimateTotal (95% CI)Test for overall effect Z=4.48 (p<0.00001)
-1.427-1.421
-0.968-1.122
0.5190.359
0.3770.304
32.4%67.6%
100.00%
39.4%60.6%
100.00%
0.24 (0.09-0.66)0.24 (0.12-0.49)0.24 (0.14-0.43)
0.38 (0.18-0.80)0.33 (0.18-0.53)0.35 (0.22-0.55)
Statistical inconsistency (I2): 0% for both comparisons
Palmerini, Biondi-Zoccai et al, Lancet 2012
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WHAT ABOUT DEATH OR MYOCARDIAL INFARCTION?
• CoCr-EES were also associated with a significantly lower risk of myocardial infarction (OR=0.61 [0.47-0.79]).
• These differences were supported by favorable trends for all cause death (OR=0.83 [0.65-1.03]) and cardiac death (OR=0.82 [0.58-1.13]).
Palmerini, Biondi-Zoccai et al, Lancet 2012
www.metcardio.org
LEARNING GOALS• Current paradigm
• Why could drug-eluting stents possibly be safer than bare-metal stents?
• The case for network meta-analyses
• Stent thrombosis with drug-eluting versus bare-metal stents: evidence from a network meta-analysis
• Paradigm shift
www.metcardio.org
IMPLICATIONS• The largest and most comprehensive appraisal
of the risk of stent thrombosis with different types of coronary stents has the following implications:– CoCr-EES were associated with significantly
lower rates of 1-year and 2-year definite stent thrombosis than were BMS, a result not present with any other DES.
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IMPLICATIONS– Decreases in stent thrombosis with CoCr-EES
compared with BMS were apparent both early and late (occurring before 30 days and between 31 days and 1 year).
– CoCr-EES were also associated with lower 1-year rates of definite stent thrombosis than were other 1st and 2nd generation DES, including PES, SES, PC-ZES, and Re-ZES.
– These benefits were associated with lower rates of myocardial infarction.
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IS THIS A PARADIGM SHIFT?
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THE REPLY IS YOURS…
IF I NEEDED A STENT TODAY, WHICH STENT SHOULD I CHOOSE?
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Many thanks for your attention
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DEFINITIONS OF STENT THROMBOSIS
Cutlip et al, Circulation 2007
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DEFINITIONS OF STENT THROMBOSIS
Cutlip et al, Circulation 2007
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DEFINITIONS OF STENT THROMBOSIS
Cutlip et al, Circulation 2007
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TIMING OF STENT THROMBOSIS
Cutlip et al, Circulation 2007