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Stent and Adjunctive Therapy Selection in 2010

Stent and Adjunctive Therapy Selection in 2010 . Ziyad Ghazzal MD, FACC, FSCAI Professor of Medicine Deputy VP/Dean; Associate Dean for Clinical Affairs American University of Beirut Adjunct Professor of Medicine Emory University School of medicine. The different types of DES on the market.

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Stent and Adjunctive Therapy Selection in 2010

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  1. Stent and Adjunctive Therapy Selection in 2010 Ziyad Ghazzal MD, FACC, FSCAIProfessor of MedicineDeputy VP/Dean; Associate Dean for Clinical AffairsAmerican University of Beirut Adjunct Professor of MedicineEmory University School of medicine

  2. The different types of DES on the market

  3. NEVO stent • Cobalt Chromium • Biodegradable polymer • Sirolimus

  4. 1st Generation 2nd Generation 3rd Generation Element™ Stent Series TAXUS™ Express™Stent TAXUS™ Liberté™ Stent Endeavor™Stent XIENCE V™Stent XIENCE™Prime™Stent Cypher™Stent DES Platform Multi-Link Vision™ Stent 0 .081 mm (0.0032” ) Cobalt Chromium Liberté™ Stent 0.096 mm(0.0038”) Stainless Steel Bx Velocity™ Stent 0.140 mm (0.0055” ) Stainless Steel Express™Stent 0.132 mm (0.0052”) Stainless Steel Element™Stent9 0.081 mm(0.0032”) Platinum Chromium Driver™ Stent 0.091 mm (0.0036”)Cobalt Chromium XIENCE Prime™ Stent 0.081 mm (0.0032”) Cobalt Chromium BMS Platform

  5. Average Stent Profile 0.043” PROMUS™ Element™ Stent 1.09mm 0.046” TAXUS™ Element™ Stent 1.17mm TAXUS™ Liberté™ Stent 0.047” 1.19mm XIENCE V™ / PROMUS™ Stent 0.042” 1.07mm XIENCE Prime™ Stent 0.044” 1.12mm Endeavor™ Resolute™ Stent 0.047” 1.19mm Cypher Select™ PlusStent 0.048” 1.22mm

  6. Platform ComparisonVessel Coverage TAXUS™ Liberté™ Stent Driver™ Stent TAXUS™Express2™ Stent Cypher™ Stent

  7. RESOLUTE All Comers Trial Euro PCR 2010 • Randomized comparison between the 2nd generation • Resolute zotarolimus-eluting stent (R-ZES) • XienceV everolimus-eluting stent (EES) • Primary non-inferiority endpoint (12-month target lesion failure) • R-ZES: 8.2% • EES: 8.3%

  8. BMS vs DES • The only advantage of DES over BMS is the reduction of restenosis (and TVR) • No difference in procedural complications • No difference in MI or mortality • DES is more expensive • The main disadvantage of DES is the reliance on DAT because of the concern about stent thrombosis

  9. BMS vs DES In clinical trials

  10. NEJM March 2007

  11. NEJM March 2007

  12. NEJM March 2007

  13. NEJM March 2007

  14. Drug Eluting Stents

  15. The risk of stent thrombosis increases for both OFF label use DES vs BMs

  16. Milan/Siegburg Experience Stent thrombosis after DES (SES or PES) occurred in 29/2229 pts (1.3%) at 9.3±5.6 mos Unstable angina Thrombus Diabetes Unprot. left main Bifurcation Renal failure Prior brachyRx Premature Plavix d/c Iakovou I. and Colombo A. et.al JAMA, May 4, 2005; 293: 2126

  17. Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents - A Science Advisory - 2007 • Discuss 12 months dual anti-platelet therapy prior to DES implantation • If surgical procedure anticipated, consider BMS or POBA • Educate patients prior to discharge on hazards of premature discontinuation of dual anti-platelet therapy • Instruct patient to call cardiologist if instructed to discontinue anti-platelets

  18. Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents – A Science Advisory - 2007 • Physicians performing invasive or surgical procedures should discuss discontinuation of therapy with patient’s cardiologist and weigh risks and benefits • Elective procedures should be delayed until 12 months of dual anti-platelet therapy is completed • If surgery cannot be delayed, ASA should be continued if at all possible and thienopyridine restarted as soon as possible

  19. Choice of oral anti-platelet therapy

  20. P2Y12 antagonists

  21. prasugrel

  22. STUDY DESIGN R Prasugrel 60 mg LD/ 10 mg MD ASA UA/NSTEMI (TIMI Risk Score ≥ 3) 12.0 month planned median & Planned PCI Double-blind treatment 6 - 15 months planned follow-up 14.5 month actual median STEMI (Primary PCI ≤ 12 hours of symptoms or post-STEMI within 14 days) ASA Clopidogrel 300 mg LD/ 75 mg MD Day 3 Day 30 Day 90 Day 450 • Primary efficacy end point: CV death, nonfatal MI or nonfatal stroke. • Key safety endpoint: TIMI major bleeding. Wiviott SD et al. New Engl J Med 2007. Wiviott SD et al. Am Heart J 2006.

  23. PRIMARY ENDPOINT 15 HR 0.77 (0.67-0.88)P<0.001 Clopidogrel 12.1(n=781) 9.9 (n=643) 10 Prasugrel CV Death/MI/Stroke (%) HR 0.81 (0.73-0.90)P<0.001ARR=2.2NNT=46 HR 0.80 (0.71-0.90)P<0.001 5 Intent To Treat: n=13,608; Lost to Follow-Up: n=14 (0.1%) 0 0 30 60 90 180 270 360 450 Days Wiviott SD et al. New Engl J Med 2007.

  24. STENT THROMBOSIS: ANY STENT 3 2 1 0 0 30 60 90 180 270 360 450 Any Stent at Index PCI n=12,844 2.35 Clopidogrel Stent Thrombosis (%) 1.13 Prasugrel HR 0.48 (0.36-0.64)P<0.0001 RRR 52% ARR 1.22% NNT=77 Days Wiviott SD et al. Lancet 2008.

  25. STENT THROMBOSIS: BMS 2.5 2.41% BMS at Index PCI n=6,461 RRR 48% 2 Clopidogrel HR 0.52 (0.35-0.77) p=0.0009 1.5 % of Subjects 1.27% Prasugrel 1 1 year: 1.22 vs 2.27% HR 0.53 (0.36-0.79)p=0.0014 0.5 0 0 50 100 150 200 250 300 350 400 450 Days Wiviott SD et al. Lancet2008.

  26. STENT THROMBOSIS: DES 2.5 DES at Index PCI n=5,743 2.31% Clopidogrel 2 RRR 64% HR 0.36 (0.22-0.58) p<0.0001 1.5 % of Subjects 1 Prasugrel 0.84% 1 year: 0.74% vs. 2.05% HR 0.35 (0.21-0.58) p<0.0001 0.5 0 450 0 50 100 150 200 250 300 350 400 Days Wiviott SD et al. Lancet2008.

  27. TRITON-TIMI 38: Life Threatening Bleeds at 15 Months (All ACS) (n=6,716) (n=6,741) P=0.01 P=0.23 1.4% End Point (%) n=85 1.1% 0.9% 0.9% n=64 P=0.002 n=56 n=51 P=0.74 0.4% 0.3% 0.3% n=21 0.1% n=19 n=17 n=5 Nonfatal Life-Threatening Fatal Intracranial Subsets of Life-threatening Bleeds Wiviott SD et al. New Engl J Med 2007;357:2001-2015 ACS=Acute Coronary Syndrome; HR=Hazard Ratio

  28. HIGH RISK POPULATIONS Subgroup

  29. ticagrelor

  30. H O N N N H H O N F O N N F S O H Ticagrelor (AZD 6140): an oral reversible P2Y12 antagonist Ticagrelor is a cyclo-pentyl-triazolo-pyrimidine (CPTP) • Direct acting • Not a prodrug; does not require metabolic activation • Rapid onset of inhibitory effect on the P2Y12 receptor • Greater inhibition of platelet aggregation than clopidogrel • Reversibly bound • Degree of inhibition reflects plasma concentration • Faster offset of effect than clopidogrel • Functional recovery of all circulating platelets

  31. Optimal clopidogrel dosing

  32. OASIS-7 CURRENT OASIS 7: A 2X2 Factorial Randomized Trial of Optimal Clopidogrel and Aspirin Dosing in Patients with ACS Undergoing an Early Invasive Strategy with Intent For PCI Shamir R. Mehta on behalf of the CURRENT Investigators Disclosures: CURRENT OASIS 7 was funded by a grant from sanofi-aventis and Bristol Myers Squibb. All data were managed independently of the sponsor at the PHRI, McMaster University and the trial was overseen by an international steering committee of experts.

  33. 25,087 ACS Patients (UA/NSTEMI 70.8%, STEMI 29.2%) • Planned Early (<24 h) Invasive Management with intended PCI • Ischemic ECG Δ (80.8%) or ↑cardiac biomarker (42%) Randomized to receive (2 X 2 factorial): CLOPIDOGREL: Double-dose(600 mg then150 mg/d x 7d then 75 mg/d) vsStandard dose (300 mg then 75 mg/d) ASA: High Dose (300-325 mg/d) vsLow dose(75-100 mg/d) Angio 24,769 (99%) PCI 17,232 (70%) No PCI 7,855 (30%) No Sig. CAD 3,616 CABG 1,809 CAD 2,430 Compliance: Clop in 1st 7d (median) 7d 7 d 2 d 7d Efficacy Outcomes: CV Death, MI or stroke at day 30 Stent Thrombosis at day 30 Safety Outcomes:Bleeding (CURRENT defined Major/Severe and TIMI Major) Key Subgroup:PCI v No PCI Complete Follow up 99.8%

  34. Clopidogrel: Double vs Standard Dose Definite Stent Thrombosis (Angio confirmed) Clopidogrel Standard Dose 0.012 42% RRR 0.008 Cumulative Hazard Clopidogrel Double Dose 0.004 HR 0.58 95% CI 0.42-0.79 P=0.001 0.0 0 3 6 9 12 15 18 21 24 27 30 Days

  35. Clopidogrel: Double vs Standard Dose Primary Outcome: PCI Patients CV Death, MI or Stroke Clopidogrel Standard 15% RRR 0.04 Clopidogrel Double 0.03 Cumulative Hazard 0.02 HR 0.85 95% CI 0.74-0.99 P=0.036 0.01 0.0 0 3 6 9 12 15 18 21 24 27 30 Days

  36. ASA Dose Comparison Death/MI/Stroke at 30 days 0.04 0.03 HR 0.96 (0.85-1.08)P = 0.489 Cumulative Hazard 0.02 0.01 ASA 81-100 mg ASA 300-325 mg 0.0 0 3 6 9 12 15 18 21 24 27 30 Days

  37. Point of care assays

  38. VerifyNow

  39. PFA-100

  40. VASP

  41. Impedance aggregometry

  42. Cone and plate analyzer

  43. Do platelet function assays predict clinical outcomes in clopidogrel pretreated patients undergoing elective PCI? POPULAR

  44. POPULAR • Light transmittance aggregometry (LTA): Peak platelet aggregation in response to 5 or 20 µmol/L ADP • VerifyNow P2Y12 assay: Aggregation based • Plateletworks: ADP stimulation-derived platelet count • Impact R: With and without ADP stimulation • PFA-100 system: Collagen/ADP stimulation • Innovance PFA P2Y: ADP, PGE1, and calcium chloride

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