Why are drug eluting stents safer than bare metal stents
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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.

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Why are drug-eluting stents safer than bare-metal stents?

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Why are drug eluting stents safer than bare metal stents

Why are drug-eluting stents safer than bare-metal stents?

Giuseppe Biondi Zoccai, MD

Sapienza UniversityofRome, Rome, Italy

METCARDIO, Ospedaletti, Italy

[email protected]

10th International Cardiology Congress – Patras – 4-6 May 2012


Learning goals

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


Learning goals1

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


What is stent thrombosis

WHAT IS STENT THROMBOSIS?


Incidence of stent thrombosis

INCIDENCE OF STENT THROMBOSIS*

very late

total

acute

subacute

late

*at a median folllow-up of 18 months

D’Ascenzo et al, Int J Cardiol 2012


Predictors of stent thrombosis

PREDICTORS OF STENT THROMBOSIS*

*number of studies confirming the independent role of the predictor

D’Ascenzo et al, Int J Cardiol 2012


Impact of stent thrombosis

IMPACT OF STENT THROMBOSIS

Chechi et al, J Am Coll Cardiol 2008


2006 annus horribilis for drug eluting stents

2006: ANNUS HORRIBILIS FOR DRUG-ELUTING STENTS


2006 annus horribilis for drug eluting stents1

2006: ANNUS HORRIBILIS FOR DRUG-ELUTING STENTS

Nordmann et al, Eur Heart J 2006

Camenzind, ESC/WCC 2006

Bavry et al, Am J Med 2006


Learning goals2

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


Potential of everolimus eluting stents

POTENTIAL OF EVEROLIMUS-ELUTING STENTS

Verheye et al, J Am Coll Cardiol 2007


Potential of everolimus eluting stents1

POTENTIAL OF EVEROLIMUS-ELUTING STENTS

Kolandaivelu et al, Circulation 2011


Risk of stent thrombosis with everolimus eluting versus bare metal stents

RISK OF STENT THROMBOSIS WITH EVEROLIMUS-ELUTING VERSUS BARE-METAL STENTS

Kaiser et al, New Engl J Med 2010

Sabate, ESC 2011


Potential of zotaroimus eluting stents

POTENTIAL OF ZOTAROIMUS-ELUTING STENTS

Guagliumi et al, J Am Coll Cardiol Intv 2010


Learning goals3

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


Meta analyses

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


Systematic review and meta analyses

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


Arguably the most important meta analysis ever

ARGUABLY THE MOST IMPORTANT META-ANALYSIS EVER….

Antman et al, JAMA 1992


Showing discrepancies among evidence and experts

…SHOWING DISCREPANCIES AMONG EVIDENCE AND EXPERTS


Standard pair wise meta analyses

STANDARD (PAIR-WISE) META-ANALYSES

Point estimate

95% confidence interval

Inconsistency

P for effect

P for heterogeneity

Summary estimate

Hsia et al, Ann Surg 2008


Indirect and network meta analyses

INDIRECT AND NETWORKMETA-ANALYSES

Biondi-Zoccai et al, HSR Proceedings 2011


Parallel hierarchy of clinical research

PARALLEL HIERARCHY OF CLINICAL RESEARCH

Biondi-Zoccai et al, HSR Proceedings 2011


Learning goals4

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


Network meta analysis of stent thrombosis

NETWORK META-ANALYSIS OF STENT THROMBOSIS

Palmerini, Biondi-Zoccai et al, Lancet 2012


Why are drug eluting stents safer than bare metal stents

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


Search and selection

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


End points

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


Analysis

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


Analysis1

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


Review profile

REVIEW PROFILE

2602 potentially relevant articles

FDA

approved

stents

(BMS, SES, PES, End-ZES, Res-ZES, CoCr-EES, PtCr-EES)

49 RCTs

50,844 pts

2441 excluded

2117 not a comparison of DES

324 post-hoc, subgroup,

follow-up, or pooled analyses

Review of title

and abstract

161 articles needing full review

112 excluded

84 not an RCT

13 DES not FDA approved

11 no ARC definition

4 DES pooled

Full-text

review

49 RCTs meeting criteria

Palmerini, Biondi-Zoccai et al, Lancet 2012


Evidence network

EVIDENCE NETWORK

9 studies

PES

BMS

9 studies

4 studies

8 studies

1 study

5 studies

2 studies

6 studies

End-ZES

SES

6 studies

CoCr-EES

2 studies

1 study

Res-ZES

PtCr-EES

Palmerini, Biondi-Zoccai et al, Lancet 2012


1 year definite stent thrombosis

1-YEAR DEFINITE STENT THROMBOSIS

Odds Ratio

[95%]

CoCr-EES vs BMS

CoCr-EES vs PES

CoCr-EES vs SESCoCr-EES vs Res-ZES

CoCr-EES vs End-ZES

SES vs BMS

End-ZES vs SES

0.23 (0.13-0.41)

0.28 (0.16-0.48)

0.41 (0.24-0.70)

0.14 (0.03-0.47)

0.21 (0.10-0.44)

0.57 (0.36-0.88)

1.92 (1.07-3.90)

1

10

0.1

0.01

Favors Stent 1

Favors Stent 2

Palmerini, Biondi-Zoccai et al, Lancet 2012


30 day definite stent thrombosis

30-DAY DEFINITE STENT THROMBOSIS

Odds Ratio [95%]

CoCr-EES vs BMS

CoCr-EES vs PES

CoCr-EES vs SESCoCr-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)

1

10

0.1

0.01

Favors Stent 2

Favors Stent 1

Palmerini, Biondi-Zoccai et al, Lancet 2012


30 day to 1 year definite stent thrombosis

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)

1

100

0.1

0.01

10

Favors Stent 1

Favors Stent 2

Palmerini, Biondi-Zoccai et al, Lancet 2012


2 year definite stent thrombosis

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)

1

10

0.1

0.01

Favors Stent 1

Favors Stent 2

Palmerini, Biondi-Zoccai et al, Lancet 2012


Other results for definite stent thrombosis

OTHER RESULTS FOR DEFINITE STENT THROMBOSIS

Palmerini, Biondi-Zoccai et al, Lancet 2012


Why are drug eluting stents safer than bare metal stents

OTHER RESULTS FOR DEFINITE STENT THROMBOSIS

Palmerini, Biondi-Zoccai et al, Lancet 2012


Other results for definite or probable stent thrombosis

OTHER RESULTS FOR DEFINITE OR PROBABLE STENT THROMBOSIS

Palmerini, Biondi-Zoccai et al, Lancet 2012


Statistical consistency

STATISTICAL CONSISTENCY

Odds Ratio IV

Random, 95% CI

Log (odds ratio)

SE

Weight

Definite stent thrombosis

32.4%

67.6%

100.00%

0.24 (0.09-0.66)

0.24 (0.12-0.49)

0.24 (0.14-0.43)

Direct estimate

Indirect estimate

Total (95% CI)

Test for overall effect Z=4.82 (p<0.00001)

-1.427

-1.421

0.519

0.359

Definite or probable thrombosis

Direct estimate

Indirect estimate

Total (95% CI)

Test for overall effect Z=4.48 (p<0.00001)

39.4%

60.6%

100.00%

0.38 (0.18-0.80)

0.33 (0.18-0.53)

0.35 (0.22-0.55)

-0.968

-1.122

0.377

0.304

Statistical inconsistency (I2):

0% for both comparisons

1

10

0.001

0.1

IV = inverse variance

SE = standard error

Favors CoCr-EES

Favors BMS

Palmerini, Biondi-Zoccai et al, Lancet 2012


What about death or myocardial infarction

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


Learning goals5

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


Implications

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.


Implications1

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.


Is this a paradigm shift

IS THIS A PARADIGM SHIFT?


The reply is yours

THE REPLY IS YOURS…

IF I NEEDED A STENT TODAY, WHICH STENT SHOULD I CHOOSE?


Why are drug eluting stents safer than bare metal stents

Many thanks for your attentionFor these and further slides on these topics please feel free to visit the metcardio.org website:http://www.metcardio.org/slides.html


Definitions of stent thrombosis

DEFINITIONS OF STENT THROMBOSIS

Cutlip et al, Circulation 2007


Definitions of stent thrombosis1

DEFINITIONS OF STENT THROMBOSIS

Cutlip et al, Circulation 2007


Definitions of stent thrombosis2

DEFINITIONS OF STENT THROMBOSIS

Cutlip et al, Circulation 2007


Timing of stent thrombosis

TIMING OF STENT THROMBOSIS

Cutlip et al, Circulation 2007


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