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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 University of Rome , Rome , Italy METCARDIO, Ospedaletti , Italy giuseppe.biondizoccai@uniroma1.it. 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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  1. Why are drug-eluting stents safer than bare-metal stents? Giuseppe Biondi Zoccai, MD Sapienza UniversityofRome, Rome, Italy METCARDIO, Ospedaletti, Italy giuseppe.biondizoccai@uniroma1.it 10th International Cardiology Congress – Patras – 4-6 May 2012

  2. 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

  3. 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

  4. WHAT IS STENT THROMBOSIS?

  5. 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

  6. PREDICTORS OF STENT THROMBOSIS* *number of studies confirming the independent role of the predictor D’Ascenzo et al, Int J Cardiol 2012

  7. IMPACT OF STENT THROMBOSIS Chechi et al, J Am Coll Cardiol 2008

  8. 2006: ANNUS HORRIBILIS FOR DRUG-ELUTING STENTS

  9. 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

  10. 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

  11. POTENTIAL OF EVEROLIMUS-ELUTING STENTS Verheye et al, J Am Coll Cardiol 2007

  12. POTENTIAL OF EVEROLIMUS-ELUTING STENTS Kolandaivelu et al, Circulation 2011

  13. RISK OF STENT THROMBOSIS WITH EVEROLIMUS-ELUTING VERSUS BARE-METAL STENTS Kaiser et al, New Engl J Med 2010 Sabate, ESC 2011

  14. POTENTIAL OF ZOTAROIMUS-ELUTING STENTS Guagliumi et al, J Am Coll Cardiol Intv 2010

  15. 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

  16. 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

  17. 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

  18. ARGUABLY THE MOST IMPORTANT META-ANALYSIS EVER…. Antman et al, JAMA 1992

  19. …SHOWING DISCREPANCIES AMONG EVIDENCE AND EXPERTS

  20. 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

  21. INDIRECT AND NETWORKMETA-ANALYSES Biondi-Zoccai et al, HSR Proceedings 2011

  22. PARALLEL HIERARCHY OF CLINICAL RESEARCH Biondi-Zoccai et al, HSR Proceedings 2011

  23. 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

  24. NETWORK META-ANALYSIS OF STENT THROMBOSIS Palmerini, Biondi-Zoccai et al, Lancet 2012

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. OTHER RESULTS FOR DEFINITE STENT THROMBOSIS Palmerini, Biondi-Zoccai et al, Lancet 2012

  37. OTHER RESULTS FOR DEFINITE STENT THROMBOSIS Palmerini, Biondi-Zoccai et al, Lancet 2012

  38. OTHER RESULTS FOR DEFINITE OR PROBABLE STENT THROMBOSIS Palmerini, Biondi-Zoccai et al, Lancet 2012

  39. 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

  40. 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

  41. 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

  42. 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.

  43. 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.

  44. IS THIS A PARADIGM SHIFT?

  45. THE REPLY IS YOURS… IF I NEEDED A STENT TODAY, WHICH STENT SHOULD I CHOOSE?

  46. 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

  47. DEFINITIONS OF STENT THROMBOSIS Cutlip et al, Circulation 2007

  48. DEFINITIONS OF STENT THROMBOSIS Cutlip et al, Circulation 2007

  49. DEFINITIONS OF STENT THROMBOSIS Cutlip et al, Circulation 2007

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