SIRIUS: Purpose <ul><li>To assess the safety and effectiveness of the  sirolimus-eluting Bx VELOCITY™ in reducing target v...
SIRIUS Study design
SIRIUS: Endpoints <ul><li>Primary: </li></ul><ul><ul><li>9m Target Vessel Failure  (cardiac death, MI, or TVR). </li></ul>...
SIRIUS: Study Design <ul><li>Principal investigators: Martin Leon and Jeffrey Moses,  Lenox Hill  </li></ul><ul><li>Study ...
SIRIUS: Study Design De Novo  Coronary Lesions  Diameter: 2.5-3.5 mm Length: 15-30 mm Control  Bx VELOCITY TM n = 556 CYPH...
SIRIUS: Pharmacologic Regimen <ul><li>Pre-procedure </li></ul><ul><ul><li>Aspirin (325mg) > 24 hrs. </li></ul></ul><ul><ul...
SIRIUS: Inclusion Criteria <ul><li>Single  de novo  coronary lesion </li></ul><ul><li>Reference vessel  >  2.5mm and  >  3...
SIRIUS: Exclusion Criteria <ul><li>Recent MI ( <  24 hours) </li></ul><ul><li>Unprotected left main disease </li></ul><ul>...
SIRIUS: Study Procedure n = 1100 pts Single  de novo  native coronary lesion Pre-dilation (balloons only) Post-dilation (h...
SIRIUS: Study Flow All Randomised Patients n = 1101 CYPHER n = 533 Control  Bx VELOCITY TM n = 525 Angio FU at 8 Months = ...
SIRIUS: Patient Demographics 32.9 28.2 Prior MI 23.1 26.3 Prior PCI 22.4 17.7 Current Smoker 67.8 67.6 Hypertension 74.6 7...
SIRIUS: Baseline Lesion Characteristics 32.4 30.0 RCA 0.6 0.6 Other 20.6 26.0 C 33.5 32.6 B2 38.1 34.0 B1 7.8 7.4 AHA/ACC ...
SIRIUS: Baseline Lesion Characteristics (2) 13.7 15.4 3 14.4  ±  5.8 14.4  ±  5.7 Mean Lesion length 13.4 15.2 >20mm 66.2 ...
SIRIUS: Stents Implanted 26.9 28.5 Patients with overlapping stents 1.4  ± 0.6 1.4  ± 0.7 Mean stents per patient (n) 21.2...
SIRIUS: Other Procedural 59.2 60.4 IIbIIIa during procedures (%) 1.2  ± 0.6 1.2  ± 0.9 Mean hospital stay (days) Control C...
SIRIUS: Control Group <ul><li>From 9,000 patient HCRI stent database, adjusting for SIRIUS case mix (vessel size, lesion l...
SIRIUS:  QCA  Definitions <ul><li>In-stent  QCA   =   within the margins of the stent. </li></ul><ul><li>In-segment  QCA =...
SIRIUS: QCA Late Loss Analysis   (9-month) Margins = 5mm either side of stent P < 0.001 P < 0.001 P < 0.001
SIRIUS  12 -month Results
SIRIUS: Clinical events (all events to 360 days) Events 24.8 (130) 22.3 (117) 6.7 (35) 1.3 (7) 5.5 (29) 19.2 (101) 3.0 (16...
SIRIUS: Clinical events (diabetics only to 360 days) Note that TLR & TVR rates are  clinically driven only  and do not inc...
Reduction in TLR by Patient Characteristics Lesion Length Reference Vessel Diameter 72.8 74.8 76.5 75.3 76.6 77.6 12mm - 1...
CP1104360-1 Freedom from events (%) Post  procedure (days) Cypher  TLR Control TLR Cypher  MACE Control MACE Cypher  TVF C...
SIRIUS: TLR Events Overall 4. 9 20.0 0.0001 1 5 2 M ale 5.2 20.5 0.0001 1 53 Female 4 .1 1 9.0 0.000 2 1 49 Diabetes 8 . 4...
SIRIUS: Stent Thrombosis * 234 days post-procedure ** 40, 150 and 181 days post-procedure 0 0 Acute (   24 hours) 0.8 (4)...
SIRIUS:  12 -month summary <ul><li>Safety </li></ul><ul><ul><li>Death & MI rates equivalent to control group. </li></ul></...
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Cypher Stent - SIRIUS Trial

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  • Cypher Stent - SIRIUS Trial

    1. 2. SIRIUS: Purpose <ul><li>To assess the safety and effectiveness of the sirolimus-eluting Bx VELOCITY™ in reducing target vessel failure in de novo native coronary artery lesions compared with the uncoated Bx stent. </li></ul><ul><li>SIRIUS was a USA-based trial. </li></ul>
    2. 3. SIRIUS Study design
    3. 4. SIRIUS: Endpoints <ul><li>Primary: </li></ul><ul><ul><li>9m Target Vessel Failure (cardiac death, MI, or TVR). </li></ul></ul><ul><li>Secondary: </li></ul><ul><ul><li>MACE at 1, 6, 9, 12m, and annually to 5 years . </li></ul></ul><ul><ul><li>Angiographic binary restenosis (  50% DS) at 8 months. </li></ul></ul><ul><ul><li>In-stent and in-lesion MLD at 8 months. </li></ul></ul><ul><ul><li>TLR and TVR at 9 months. </li></ul></ul><ul><ul><li>Device success, lesion success, and procedure success (in-hospital). </li></ul></ul><ul><ul><li>Economic factors – index hospitalisation costs, length of stay, and repeat hospitalisations (for up to 12 months). </li></ul></ul>
    4. 5. SIRIUS: Study Design <ul><li>Principal investigators: Martin Leon and Jeffrey Moses, Lenox Hill </li></ul><ul><li>Study coordination: Richard Kuntz, Brigham & Women’s Hospital. </li></ul><ul><li>Angiographic core lab: Jeffrey Popma, Brigham & Women’s Hospital. </li></ul><ul><li>IVUS core lab: Peter Fitzgerald, Stanford (Palo Alto) </li></ul><ul><li>Economic core lab: David Cohen, Beth Israel (Boston) </li></ul><ul><li>Industry sponsor: Cordis. </li></ul>
    5. 6. SIRIUS: Study Design De Novo Coronary Lesions Diameter: 2.5-3.5 mm Length: 15-30 mm Control Bx VELOCITY TM n = 556 CYPHER TM n = 545 n = 1101 patients Angiographic Sub-study: first 850 pts (FU at 8 months) IVUS Substudy: 250 pts at selected sites (FU at 8 months)
    6. 7. SIRIUS: Pharmacologic Regimen <ul><li>Pre-procedure </li></ul><ul><ul><li>Aspirin (325mg) > 24 hrs. </li></ul></ul><ul><ul><li>Clopidogrel (loading dose, 75mg/day) or Ticlopidine (loading dose, 250mg/2x day) </li></ul></ul><ul><li>During procedure </li></ul><ul><ul><li>Heparin (bolus and additional to maintain ACT > 250 secs) </li></ul></ul><ul><ul><li>IIb/IIIa inhibitors – operator discretion </li></ul></ul><ul><li>Post-procedure </li></ul><ul><ul><li>Aspirin (325mg/day) – indefinitely </li></ul></ul><ul><ul><li>Clopidogrel (75mg/day) or Ticlopidine (250mg/2x day) </li></ul></ul>} > 24hrs } 3 months
    7. 8. SIRIUS: Inclusion Criteria <ul><li>Single de novo coronary lesion </li></ul><ul><li>Reference vessel > 2.5mm and > 3.5 mm * </li></ul><ul><li>Lesion length: > 15mm and < 30mm * </li></ul><ul><li>Diameter Stenosis: > 50% and < 100% </li></ul><ul><li>CCS angina or unstable angina (Braunwald B&C, I-II) or documented silent ischaemia </li></ul>* Visual estimate
    8. 9. SIRIUS: Exclusion Criteria <ul><li>Recent MI ( < 24 hours) </li></ul><ul><li>Unprotected left main disease </li></ul><ul><li>Ostial location </li></ul><ul><li>Total occlusion (TIMI 0 flow) </li></ul><ul><li>Angiographic evidence of thrombus </li></ul><ul><li>Calcified lesion which cannot be predilated </li></ul><ul><li>LV ejection fraction < 25% </li></ul><ul><li>Impaired renal function </li></ul><ul><li>Pretreatment with devices other than balloon angioplasty </li></ul><ul><li>Allergy to aspirin or clopidogrel (ticlopidine) </li></ul><ul><li>Prior or planned intervention within 30 days </li></ul>
    9. 10. SIRIUS: Study Procedure n = 1100 pts Single de novo native coronary lesion Pre-dilation (balloons only) Post-dilation (high pressure balloons) Bx – Sirolimus vs. non-coated
    10. 11. SIRIUS: Study Flow All Randomised Patients n = 1101 CYPHER n = 533 Control Bx VELOCITY TM n = 525 Angio FU at 8 Months = 85.4% Clinical FU at 9 Months = 95.7% Angio FU at 8 Months = 84.7% Clinical FU at 9 Months = 95.8% De-registered CYPHER (n=23) De-registered Control Bx VELOCITY TM (n=20)
    11. 12. SIRIUS: Patient Demographics 32.9 28.2 Prior MI 23.1 26.3 Prior PCI 22.4 17.7 Current Smoker 67.8 67.6 Hypertension 74.6 72.6 Hyperlipidaemia 28.2 24.6 Diabetes Mellitus 62.4 62.1 Mean age (years) 69.7 72.6 Male Control (%) (n=525) CYPHER (%) (n=533)
    12. 13. SIRIUS: Baseline Lesion Characteristics 32.4 30.0 RCA 0.6 0.6 Other 20.6 26.0 C 33.5 32.6 B2 38.1 34.0 B1 7.8 7.4 AHA/ACC A 23.9 25.3 LCx 43.2 44.2 LAD Control (%) (n=525) CYPHER (%) (n=533)
    13. 14. SIRIUS: Baseline Lesion Characteristics (2) 13.7 15.4 3 14.4 ± 5.8 14.4 ± 5.7 Mean Lesion length 13.4 15.2 >20mm 66.2 64.8 10-20mm 20.4 20.0 Lesion length <10mm 28.8 25.3 2 57.5 59.3 No. of diseased coronaries 1 Control (%) (n=525) CYPHER (%) (n=533)
    14. 15. SIRIUS: Stents Implanted 26.9 28.5 Patients with overlapping stents 1.4 ± 0.6 1.4 ± 0.7 Mean stents per patient (n) 21.2 ± 6.8 21.5 ± 6.7 Stent length (mm) 0.8 1.5  4 4.6 4.9 3 29.5 28.6 2 37.0 35.1 3.5 64.9 65.0 Number of stents per patient 1 45.8 45.6 3.0 17.2 19.3 Diameter 2.5 Control (%) CYPHER (%)
    15. 16. SIRIUS: Other Procedural 59.2 60.4 IIbIIIa during procedures (%) 1.2 ± 0.6 1.2 ± 0.9 Mean hospital stay (days) Control CYPHER
    16. 17. SIRIUS: Control Group <ul><li>From 9,000 patient HCRI stent database, adjusting for SIRIUS case mix (vessel size, lesion length, % diabetes) </li></ul><ul><li>Predicted in-segment restenosis = 31% </li></ul>
    17. 18. SIRIUS: QCA Definitions <ul><li>In-stent QCA = within the margins of the stent. </li></ul><ul><li>In-segment QCA = in-stent + 5mm prox & distal margins . </li></ul>5 mm 5 mm 5 mm In-segment in-stent proximal distal
    18. 19. SIRIUS: QCA Late Loss Analysis (9-month) Margins = 5mm either side of stent P < 0.001 P < 0.001 P < 0.001
    19. 20. SIRIUS 12 -month Results
    20. 21. SIRIUS: Clinical events (all events to 360 days) Events 24.8 (130) 22.3 (117) 6.7 (35) 1.3 (7) 5.5 (29) 19.2 (101) 3.0 (16) 20.0 (105) 1.7 (9) 3.4 (18) 0.8 (4) Control % n = 525 0.449 <0.001 0.295 2.3 (12) 4.9 (26) 0.9 (5) Non Q-wave TLR TLR-CABG <0.001 4.3 (23) TLR-PCI <0.001 9.8 (52) TVF <0.001 8.3 (44) MACE <0.001 3.6 (19) 0.6 (3) 3.2 (17) TVR (non TLR) TVR-CABG TVR-PCI 0.723 3.0 (16) MI (all) 0.547 1.3 (7) Death P-value CYPHER % n = 533
    21. 22. SIRIUS: Clinical events (diabetics only to 360 days) Note that TLR & TVR rates are clinically driven only and do not include angiographically driven procedures Events 29.1 (43) 8.1 (12) 0.0 (0) 8.1 (12) 25.0 (37) 4.1 (6) 26.4 (39) 2.0 (3) 4.1 (6) 0.7 (1) Control % n = 148 1.5 (2) 8.4 (11) 0.8 (1) Non Q-wave TLR TLR-CABG 8.4 (11) TLR-PCI 11.5 (15) MACE 5.3 (7) 0.0 (0) 5.3 (7) TVR (non TLR) TVR-CABG TVR-PCI 2.3 (3) MI (all) 1.5 (2) Death CYPHER % n = 131
    22. 23. Reduction in TLR by Patient Characteristics Lesion Length Reference Vessel Diameter 72.8 74.8 76.5 75.3 76.6 77.6 12mm - 15mm 75.7 77.0 2.5mm < RVD < 3.0mm 74.1 75.9 RVD < 2.5mm 70.8 73.8 RVD < 2.5mm 73.4 75.5 2.5mm < RVD < 3.0mm 75.6 76.9 RVD > 3.0mm Diabetics 77.0 77.8 RVD > 3.0mm Non-Diabetics > 15mm < 12mm
    23. 24. CP1104360-1 Freedom from events (%) Post procedure (days) Cypher TLR Control TLR Cypher MACE Control MACE Cypher TVF Control TVF Event-free survival at 1 year for TLR, MACE & TVF
    24. 25. SIRIUS: TLR Events Overall 4. 9 20.0 0.0001 1 5 2 M ale 5.2 20.5 0.0001 1 53 Female 4 .1 1 9.0 0.000 2 1 49 Diabetes 8 . 4 2 6.4 0.000 2 1 80 No Diabetes 3. 7 1 7.6 0.0001 1 38 LAD 6 . 0 23.0 0.0001 17 0 Non-LAD 4 .1 18.0 0.0001 1 4 0 Small Vessel (<2.75) 6. 6 22 . 3 0.0001 15 7 Large Vessel 3.1 18.2 0.0001 1 51 Short Lesion 4.0 1 8.6 0.0001 1 46 Long Lesion (>13.5) 6.0 2 1 .9 0.0001 1 58 Overlap 5 .7 23 . 2 0.000 1 1 75 No Overlap 4.5 1 8.6 0.0001 1 4 1 Hazards Ratio 95% CI 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0.7 0.8 0.9 CYPHER Control P-value CYPHER better # events prevented per 1,000 patients
    25. 26. SIRIUS: Stent Thrombosis * 234 days post-procedure ** 40, 150 and 181 days post-procedure 0 0 Acute (  24 hours) 0.8 (4) 0.6 (3)** 0.2 (1) Control n=525 % (n) 0.4 (2) Total 0.2 (1)* Late (31- 36 0 days) 0.2 (1) Sub-acute (1-30 days) CYPHER n=533 % (n)
    26. 27. SIRIUS: 12 -month summary <ul><li>Safety </li></ul><ul><ul><li>Death & MI rates equivalent to control group. </li></ul></ul><ul><ul><li>Low Thrombosis rate despite only 3-months anti-platelet therapy. </li></ul></ul><ul><ul><li>Cypher overlap continues to be safe. </li></ul></ul><ul><li>Clinical </li></ul><ul><ul><li>Reduction in TLR rates from 20% to 4.9% for overall study group. </li></ul></ul><ul><ul><li>Diabetic TLR reduced from 26.4% to 8.4%. </li></ul></ul><ul><ul><li>70-80% relative reduction in TLR in high risk sub-groups. </li></ul></ul>

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