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New-generation drug-eluting stents and dual antiplatelet therapy : overview

New-generation drug-eluting stents and dual antiplatelet therapy : overview. Giuseppe Biondi Zoccai, MD Department of Medico-Surgical Sciences and Biotechnologies Sapienza University of Rome , Rome , Italy giuseppe.biondizoccai@uniroma1.it. Our original sin….

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New-generation drug-eluting stents and dual antiplatelet therapy : overview

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  1. New-generationdrug-elutingstents and dual antiplatelet therapy: overview Giuseppe Biondi Zoccai, MD DepartmentofMedico-SurgicalSciences and Biotechnologies Sapienza UniversityofRome, Rome, Italy giuseppe.biondizoccai@uniroma1.it

  2. Ouroriginalsin…

  3. An ongoing challenge after stenting: preventingboth… THROMBOSIS BLEEDING

  4. Choice of aspirin was empirical from the beginning… In the first reported case of PTCA by Andreas Gruentzig, 3 days of aspirin was empirically added to heparintherapy Gruentzig et al. NEJM 1979

  5. Additionofticlopidineafter stenting wasempiric at first and then confirmedby more sound data ASA ASA plus OAC 30-day stent thrombosis rate (%) DAPT

  6. The CREDO RCT of 1- vs 12-month* DAPT: 1-year death, MI and stroke *1-month regimendidnot include clopidogrel front-loading Steinhubl et al. JAMA 2002

  7. The PCI-CURE RCT of 0- vs 12-month DAPT: 1-year CV death or MI Mehta et al. Lancet 2001

  8. The TRITON RCT of 6- to 15-month* DAPT with clopidogrel vs prasugrel: stent thrombosis† *median 14.5 months; †definite or probable Wiviott et al. Lancet 2008

  9. The PLATO RCT of 6- to 12-month* DAPT with clopidogrel vsticagrelor: stent thrombosis† *median 9.3 months; †definite, probable or possible Cannon et al. Lancet 2010

  10. The PLATO RCT of 6- to 12-month* DAPT with clopidogrel vsticagrelor: all cause death *median 14.5 months Cannon et al. Lancet 2010

  11. The Duke observationalstudywith CYPHER and TAXUS: 2-year events Eisenstein et al. JAMA 2005

  12. The VA observationalstudywith CYPHER and TAXUS: eventsafterdiscontinuing DAPT Ho et al. JAMA 2008

  13. The J-CYPHER observational study: 2-year stent thrombosis Kimura et al. Circulation 2009

  14. The Milan-Naples-Siegburgobservational studywith TAXUS and CYPHER Airoldi et al. Circulation 2007

  15. The LATE RCTs of 12- vs 24-month DAPT: 2-year death, MI and stroke Park et al. NEJM 2010

  16. The PRODIGY RCT of 6- vs 24-month DAPT: 2-year death, MI and stroke Valgimigli et al. Circulation 2012

  17. The PRODIGY RCT of 6- vs 24-month DAPT: 2-year type II, III, or V BARC bleeding Valgimigli et al. Circulation 2012

  18. The EXCELLENT RCT of 6- vs 12-month DAPT: 1-year target vessel failure Gwon et al. Circulation 2012

  19. The EXCELLENT RCT of 6- vs 12-month DAPT: other 1-year events Gwon et al. Circulation 2012

  20. Uncertainty will persist for some time: ongoing studies on DAPT

  21. 2010: ESC Guidelines on PCI/CABG

  22. 2011: ESC Guidelines on NSTEACS

  23. The XIENCE V USA studyincluding 5,054 unselectedreal-worldpatients AMI 18.1% Left Main 1.6% ACS 37.5% Graft Lesion 4.8% Renal Insufficiency 11.1% CTO Lesion 2.5% A Real-World Population EF < 30% 3.4% Direct Stenting 38.7% Diabetes 35.6% Restenosis Lesion 9.5% Multivessel Disease 40.8% Bifurcation 9.0% Multivessel Treated 13.8% Ostial 11.9% Hermiller, PCR 2010

  24. The XIENCE USA study: DAPT details Hermiller, PCR 2010

  25. The XIENCE USA study: stent thrombosis accordingto DAPT interruption Hermiller, PCR 2010

  26. The SPIRIT/XIENCE pooledanalysis on 11,219 patients: includedstudies Stone, TCT 2011

  27. The SPIRIT/XIENCE pooledanalysis on 11,219 patients: 2-year stent thrombosis Stone, TCT 2011

  28. The SPIRIT/XIENCE pooledanalysis on 11,219 patients: complianceto DAPT Stone, TCT 2011

  29. The SPIRIT/XIENCE pooledanalysis on 11,219 patients: stent thrombosisaccordingto DAPT DAPT interruptionafter 90 days DAPT interruptionwithin 90 days No DAPT interruption Stone, TCT 2011

  30. The SPIRIT/XIENCE pooledanalysis on 11,219 patients: daysof DAPT discontinuation Stone, TCT 2011

  31. The SPIRIT/XIENCE pooled analysis on 11,219 patients: stent thrombosis according to DAPT Stone, TCT 2011

  32. The SPIRIT/COMPARE pooledanalysis on 6,789 patients: includedstudies Kedhi, ACC 2011

  33. The SPIRIT/COMPARE pooledanalysis on 6,789 patients: stent thrombosisaccordingto DAPT 1-6 mo DAPT 6-12 mo DAPT 12-24 mo DAPT >24 mo DAPT Kedhi, ACC 2011

  34. The SPIRIT/XIENCE meta-analysis on 10,615 patients: includedstudies Palmerini, PCR 2012

  35. The SPIRIT/XIENCE meta-analysis on 10,615 patients: stent thrombosisaccordingto DAPT Palmerini, PCR 2012

  36. CE mark indication for XIENCE 3-month DAPT Language from CE IFU Section 8.1 for XIENCE: XIENCE demonstrated low stent thrombosis rates in patients who either discontinued or interrupted Dual Antiplatelet Therapy (DAPT) after 3 months post stent implantation. It is therefore recommended that patients treated with XIENCE stents remain on DAPT for at least 3 months after stent implantation. New indication underlines the XIENCE safety outcomes even when patients interrupt  DAPT after 3 months

  37. 3 Months DAPT CE Submission Data CE mark indication for XIENCE 3-month DAPT PCR 2012 • XIENCE V USA • ST and DAPT Interruption • at 3 Months1 • All Comer Population (n=5,054) • ST rate after DAPT interruption beyond 3 months was low and numerically similar to no DAPT interruption through 1 year • Mega-Meta Analysis • ST & DAPT Interruption • at 3 Months2 • 7 XIENCE Trials (n=13,259) • ST rate after DAPT interruption beyond 3 months was low and numerically similar to no DAPT interruption through 2 years • Real World Pooled Analysis: • 3 Months DAPT Analysis3 • All Comer Population • 4 XIENCE Trials • (n=10,615) • XIENCE shows 0% ST after DAPT interruption from 3 to 12 months Source: 1. Based on data from the XIENCE V USA trial (Hermiller PCR 2012). 2. Based on data from the Mega-Meta Analysis of 7 XIENCE trials (Stone, TCT 2011). 3. Based on data from SPIRIT/XIENCE analysis (Palmerini PCR 2012).

  38. Additionalinsightsfrom a comprehensive network meta-analysis Palmerini, Biondi-Zoccai et al, Lancet 2012

  39. 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

  40. Additionalinsightsfrom a comprehensive network meta-analysis Odds Ratio [95%] • 1-Year Definite • Stent Thrombosis 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

  41. Statisticalconsistency • Statistical consistency or homogeneity is a measure of how similar are the estimates stemming from head-to-head RCTs and the indirect comparison 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 Statisticalinconsistency (I2): 0% forbothcomparisons 1 10 0.001 0.1 IV = inverse variance SE = standard error Favors CoCr-EES Favors BMS Palmerini, Biondi-Zoccai et al, Lancet 2012

  42. Other new-degeneration DES Raberet al, JAMA 2012

  43. Othernew-degeneration DES Raberet al, JAMA 2012

  44. Prototypicalclinicalcases

  45. The Good: ↓ riskof TLRand↓ riskofbleedingwithlong-term DAPT 46-year-old ♂ witheffort angina: RCA asculprit

  46. The Bad: ↑riskof TLRbut↓ riskofbleedingwithlong-term DAPT • 61-year-old ♀with STEMI: LAD asculprit

  47. The Ugly: ↑riskof TLR and ↑ riskofbleedingwithlong-term DAPT 74-year-old ♂ with NSTEMI & AF requiringoralanticoagulants: LM-LAD asculprit

  48. Take home messages • DAPT aimstopreventtwodifferentevents: stent thrombosis and non-targetlesionthrombosis. • Long-term DAPT reduces the riskofnon-targetlesionevents. • However, thereismountinguncertainty on the impact oflong-term DAPT on stent thrombosis. • EES havea uniquesafetyprofileamongcoronarystents: • After 3 months, patientswithEES discontinuing DAPT have a riskof stent thrombosissimilartothosenotdiscontinuing;

  49. Take home messages • Accordingly, 3-month DAPT appearsadequateto reduce the riskof stent thrombosis in patientsreceivingEES; • Favorable yetmuchlessthoroughresultshavealsobeenreportedfor BES. • I personally do notrecommend 3-month DAPT in allpatients, butsurely do in carefullyselectedones. • Moreover, I can betrulyconfidentthatanyofmypatientswhohasreceived a EES and discontinue DAPT ≥3 monthsisnot put at a higherriskof stent thrombosis. • Thispropertycannot so far beinferredforanyother DES, and thusmakesEES a unique treatment opportunitytomaximizeefficacy and safety.

  50. ThankyouforyourattentionForanycorrespondence: giuseppe.biondizoccai@uniroma1.itForthese and furtherslides on thesetopicsfeel free tovisit the metcardio.org website: http://www.metcardio.org/slides.html Meta-analysis and Evidence-based medicine Training in Cardiology

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