Second Generation DES Associated with Less Late and Very Late Stent Thrombosis Compared to First Generation DES Donald E. Cutlip, MD Beth Israel Deaconess Medical Center Harvard Clinical Research Institute Harvard Medical School

Disclosures Salary support from Harvard Clinical Research Institute, an academic research organization that performs contracted research for many coronary device manufacturers Principal Investigator – Medtronic dual anti- platelet therapy after stenting trial (paid to institution) Consultant – St. Jude Medical (fellows’ course speaker)

Preliminary Considerations Impact of late and very late ST relative to early ST Differences within and between DES “generations” Is study duration of follow-up adequate to address the question? Duration of DAPT and impact on late and very late ST rates

Timing of Stent Thrombosis Academic Research Consortium Early (0-30 days) Acute (0-24 hours) Subacute (1-30 days) Late (31 days – 1 year) Very Late (> 1 year)

Timing of Stent Thrombosis Five Year Results of SES and PES RCTs

Timing of Stent Thrombosis Late Results High Risk Patients

Timing of Stent Thrombosis ACS Patients TRITON TIMI 38 ARC Definite or Probable ST HORIZONS-AMI ARC Definite or Probable ST S Wiviott et al. Lancet 2008;371:1353-63 G Stone et al. NEJM 2009;360:1946-59

Early or Late ST & 2nd Generation DES Zotarolimus-Eluting Stent Pooled Endeavor Endeavor 4 SORT-OUT III N= 2132 N= 596 N= 760 N= 756 N= 1162 N= 1170 L Mauri et al JACC Int 2010;3;1240-9 MB Leon et al JACC 2010;55;543-54 K Rasmussen et al Lancet 2010;375;1090-9

Early or Late ST & 2nd Generation DES Everolimus-Eluting Stent Pooled SPIRIT II, III, IV and COMPARE E Kedhi et al. AHA 2010

Early or Late ST & 2nd Generation DES Everolimus-Eluting Stent EES vs SES – SORT-OUT IV SES N= 1384 EES N= 1390 SES N= 1384 EES N= 1390 LO Jensen et al. TCT 2010

Very Late Stent Thrombosis Are 2nd generation DES safer? Is there increased risk after PES vs SES? Meta analysis of clinical trials, ST >6 months lower for SES vs PES (HR 0.5, 95% CI 0.3-0.8) Network meta-analysis, LST + VLST higher for PES vs BMS or SES. PES independent predictor of LST or VLST in at least 2 large registries: Western Denmark, (RR 3.8, 95% CI 2.1-7.2) Bern-Rotterdam, (HR 1.7, 95% CI 1.1-2.6) A Schömig et al. JACC 2007;50:1373 C Stettler et al. Lancet 2007;370:937-48 LO Jensen et al. Eurointerv 2010;5:898-905 P Wenaweser et al. JACC 2008;52:1134-40

Very Late Stent Thrombosis EES versus PES SPIRIT III Four Years – ARC Definite or Probable ST G Stone et al. TCT 2010

Very Late Stent Thrombosis ZES versus PES Endeavor IV– Three Year ARC Definite or Probable ST (0.1% vs. 1.6%, p=0.004) MB Leon et al JACC Intv 2010;3;1043-50

ZES Pooled Stent Thrombosis 5% 3% 0% 4% 2% 1% BMS ZES 2132 ZES pts 2 ST year 1-2; 1 ST after year 2 Cumulative Incidence of Def/Prob Thrombosis Adjusted HR = 0.50 (0.17-1.47) 1.7% Indeed with data now over 4 years – in a non randomized comparison of the ZES experiecne compared with the BMS counterpart the overall rate of ST with ZES is actually lower. Events after1 year are very infrequent in both devices with only 2 ZES ST after 1 year and 1 after 2 years in the combined experience with nearly 1200 pts now out to 5 years. 0.8% 360 720 1080 1440 1800 Time after Initial Procedure (days) L Mauri et al JACC Int 2010;3;1240-9

% Thienopyridine Usage Over Time DAPT Duration % Thienopyridine Usage Over Time SPIRIT III ENDEAVOR IV Time EES PES 12 M 71% 24 M 56% 60% 36 M 51% 48 M 49% 46% Time ZES PES 12 M 58% 57% 24 M 65% 71% 36 M 48% 52% G Stone et al. TCT 2010 M Leon et al. TCT 2009

Bioabsorbable Polymers Biolimus vs. Sirolimus-Eluting - LEADERS Trial BES 857 846 808 797 787 774 732 SES 850 841 801 792 779 758 715 P Serruys et al TCT 2010

Bioabsorbable Everolimus-Eluting Coronary Stent System (BVS) Bioabsorbable DES Bioabsorbable Everolimus-Eluting Coronary Stent System (BVS) ABSORB-A N=30 No stent thrombosis to 4 years ABSORB-B N=101 No stent thrombosis to 9M Late loss = 0.43 (recoil) Late loss = 0.19 P Serruys AHA 2010

Conclusions Early stent thrombosis remains a critical determinant of overall stent thrombosis risk (especially in high-risk lesions) EES may have slightly lower risk for early stent thrombosis compared with PES ZES appears to have the lowest risk for very late stent thrombosis but no evidence for lower early risk The optimal duration of dual anti-platelet therapy to mitigate the risk of stent thrombosis for a given DES remains unknown and must be considered in stent vs stent comparisons