CYPHER® Stent vs. Taxus Stent: Randomized Trials - Adnan Kastrati

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CYPHER® Stent vs. Taxus Stent: Randomized Trials - Adnan Kastrati

  1. 1. CYPHER ® Stent vs. Taxus Stent: Randomized Trials Kastrati A., et al., ACC 2007 Oral Presentation.
  2. 2. The ACC/AHA and ESC Guidelines <ul><li>American College of Cardiology/American Heart Association (ACC/AHA) Style </li></ul><ul><li>Classification of Evidence 1 : </li></ul><ul><li>Level of Evidence A: Data derived from multiple randomized clinical trials </li></ul><ul><li>Level of Evidence B: Data derived from a single randomized trial or nonrandomized studies </li></ul><ul><li>Level of Evidence C: Consensus opinion of experts. </li></ul>1 Smith, et al., JACC 2001; 37: 2215-38. 2 Silber S., et al., EHJ 2005; 26:804-47. <ul><li>European Society of Cardiology (ESC) Classification of Evidence 2 : </li></ul><ul><li>Level of Evidence A: Data derived from multiple randomized clinical trials or meta-analyses </li></ul><ul><li>Level of Evidence B: Data derived from a single randomized trial or large non-randomized studies </li></ul><ul><li>Level of Evidence C: Consensus opinion of experts and / or small studies, retrospective studies, registries </li></ul>
  3. 3. Keeley et al, Lancet 2003 Meta-analysis of RCTs 70 80 90 100 1 2 3 4 0 Thrombolysis PTCA time after discharge (years) survival (%) Every et al, NEJM 1996 Registry Study Randomized vs. Observational Studies: Lessons from AMI Studies Kastrati A., et al., ACC 2007 Oral Presentation.
  4. 4. Cheung et al, Br J Clin Pharmacol 2004 Simva Prava Prava Lova Prava Simva Fluva Prava Atorva Uniformity of results across RCTs is rarely achieved Kastrati A., et al., ACC 2007 Oral Presentation. Uniformity of RCT Results: Lessons from Statin Studies
  5. 5. To assess and compare long-term outcomes in randomized trials of sirolimus-eluting stents (SES) vs. paclitaxel-eluting stents (PES) Objective of the Meta-Analysis Kastrati A., et al., ACC 2007 Oral Presentation.
  6. 6. <ul><li>Randomized trial, published or presented at meetings assessing sirolimus-eluting stent (SES) vs. paclitaxel-eluting stent (PES) </li></ul>Inclusion Criteria Kastrati A., et al., ACC 2007 Oral Presentation.
  7. 7. <ul><li>Outcomes of interest : </li></ul><ul><li>- Stent thrombosis </li></ul><ul><li>- All-cause mortality </li></ul><ul><li>Composite of death or myocardial infarction (MI) </li></ul><ul><li>Composite of death, MI or reintervention (MACE) </li></ul><ul><li>during the entire available follow-up interval </li></ul>Study Endpoints Kastrati A., et al., ACC 2007 Oral Presentation.
  8. 8. <ul><li>Mantel-Cox method for calculating hazard ratios for individual trials </li></ul><ul><li>Fixed and random effect models for calculating overall harzard ratios and check for heterogeneity </li></ul><ul><li>Kaplan-Meier survival curves for all trials combined </li></ul>Statistical Methods Kastrati A., et al., ACC 2007 Oral Presentation.
  9. 9. Overall TAXI SORT-OUT II REALITY ISAR-SMART 3 ISAR-DIABETES ISAR-DESIRE CORPAL BASKET Trial LONGDES II 7,480 202 2,098 1,353 360 250 200 652 545 Total No. of patients 500 Mean Clinical FU in months 36.9 9.0 24.1 33.9 32.1 33.9 30.5 18.2 13.0 20.0 PROSIT 308 12.0 SIRTAX 1,012 24.2 Included SES vs. PES Trials Kastrati A., et al., ACC 2007 Oral Presentation.
  10. 10. Overall Trial 5,074 Total No. of patients Mean Clinical FU in months TAXI 202 36.9 REALITY 1,353 24.1 ISAR-SMART 3 360 33.9 ISAR-DIABETES 250 32.1 ISAR-DESIRE 200 33.9 CORPAL 652 30.5 BASKET 545 18.2 LONGDES II 500 13.0 25.1 SIRTAX 1,012 24.2 Trials That Provide Individual Patient Data Kastrati A., et al., ACC 2007 Oral Presentation.
  11. 11. Patients at Risk SES PES 2539 2535 2483 2457 2319 2311 2151 2121 1653 1603 573 533 Probability of Stent Thrombosis, % 0 1 2 3 4 5 0 6 12 18 24 30 Paclitaxel-eluting stent Sirolimus-eluting stent Months After Randomization Cumulative Incidence of Stent Thrombosis Kastrati A., et al., ACC 2007 Oral Presentation.
  12. 12. TAXI SIRTAX REALITY LONG-DES II ISAR-SMART 3 ISAR-DIABETES ISAR-DESIRE CORPAL BASKET Overall .1 10 1 4/264 5/281 2/331 4/321 0/100 2/100 0/125 2/125 1/180 1/180 1/250 5/250 6/684 18/669 12/503 15/509 2/102 2/100 28/2693 56/2689 Trial No. of events / Total No. of patients SES group PES group Favors SES Favors PES Hazard Ratio 0.54 (0.34, 0.85) Test for Heterogeneity: Cochran Q = 5.3 ( d.f .=9) P =.81 Test for Inconsistency: I 2 =0.0% PROSIT 0/154 2/154 SORT-OUT II NA Risk of Stent Thrombosis Kastrati A., et al., ACC 2007 Oral Presentation.
  13. 13. 0.24 0.54 0.34 0.85 1.08 BASKET CORPAL ISAR-DESIRE ISAR-DIABETES ISAR-SMART 3 LONG-DES II PROSIT REALITY SIRTAX TAXI Study ommited Meta-analysis random-effects estimates (exponential form) Influence of Individual Trials Kastrati A., et al., ACC 2007 Oral Presentation.
  14. 14. Patients at Risk SES PES 2539 2535 2498 2475 2336 2338 2170 2152 1666 1631 608 552 50 60 70 80 90 100 0 6 12 18 24 30 Paclitaxel-eluting stent Sirolimus-eluting stent Months After Randomization Probability of Survival, % Kastrati A., et al., ACC 2007 Oral Presentation. Kaplan-Meier (K/M) Curves of Survival
  15. 15. TAXI SIRTAX REALITY LONG-DES II ISAR-SMART 3 ISAR-DIABETES ISAR-DESIRE CORPAL BASKET Overall .1 10 1 10/264 11/281 18/331 22/321 8/100 6/100 21/125 22/125 10/180 13/180 2/250 0/250 23/684 23/669 25/503 25/509 7/102 3/100 148/3758 153/3722 Trial No. of events / Total No. of patients SES group PES group Favors SES Favors PES Test for Heterogeneity: Cochran Q = 5.3 ( d.f .=10) P =.87 Test for Inconsistency: I 2 =0.0% Hazard Ratio 0.93 (0.74, 1.16) PROSIT 5/154 9/154 SORT-OUT II 19/1065 19/1033 Risk of Death Kastrati A., et al., ACC 2007 Oral Presentation.
  16. 16. Patients at Risk SES PES 2539 2535 2401 2361 2236 2230 2080 2043 1596 1545 581 529 50 60 70 80 90 100 0 6 12 18 24 30 Paclitaxel-eluting stent Sirolimus-eluting stent Months After Randomization Probability of Survival Free of MI, % Kastrati A., et al., ACC 2007 Oral Presentation. K/M Curves of Survival Free of MI
  17. 17. TAXI SIRTAX REALITY LONG-DES II ISAR-SMART 3 ISAR-DIABETES ISAR-DESIRE CORPAL BASKET Overall .1 10 1 23/264 29/281 33/331 37/321 11/100 10/100 26/125 26/125 19/180 19/180 22/250 27/250 54/684 69/669 41/503 46/509 11/102 10/100 240/2539 273/2535 Trial No. of events / Total No. of patients SES group PES group Favors SES Favors PES Test for Heterogeneity: Cochran Q = 1.2 ( d.f .=8) P =.99 Test for Inconsistency: I 2 =0.0% Hazard Ratio 0.86 (0.72, 1.02) Risk of Death or MI Kastrati A., et al., ACC 2007 Oral Presentation.
  18. 18. Patients at Risk SES PES 2539 2535 2374 2313 2114 2061 1941 1855 1468 1371 527 467 50 60 70 80 90 100 0 6 12 18 24 30 Paclitaxel-eluting stent Sirolimus-eluting stent Months After Randomization Probability of Survival Free of MACE, % Kastrati A., et al., ACC 2007 Oral Presentation. K/M Curves of Survival Free of MACE
  19. 19. TAXI SIRTAX REALITY LONG-DES II ISAR-SMART 3 ISAR-DIABETES ISAR-DESIRE CORPAL BASKET Overall .1 10 1 32/264 35/281 51/331 52/321 23/100 37/100 30/125 30/125 34/180 47/180 27/250 42/250 93/684 104/669 57/503 87/509 14/102 9/100 453/3758 550/3722 Trial No. of events / Total No. of patients SES group PES group Favors SES Favors PES Test for Heterogeneity: Cochran Q = 12.2 ( d.f .=10) P =.27 Test for Inconsistency: I 2 =18.2% Hazard Ratio 0.79 (0.69, 0.91) PROSIT 9/154 18/154 SORT-OUT II 83/1065 89/1033 Kastrati A., et al., ACC 2007 Oral Presentation. Risk of MACE
  20. 20. 0.65 0.79 0.69 0.91 0.95 BASKET CORPAL ISAR-DESIRE ISAR-DIABETES ISAR-SMART 3 LONG-DES II PROSIT REALITY SIRTAX SORT-OUT II TAXI Study ommited Meta-analysis random-effects estimates (exponential form) Kastrati A., et al., ACC 2007 Oral Presentation. Influence of Individual Trials
  21. 21. <ul><li>With ~7500 patients randomized between CYPHER ® and Taxus drug-eluting stents, we are provided with the most abundant evidence of randomized stent vs. stent trials ever accumulated. </li></ul><ul><li>There is no significant heterogeneity across trials with respect to the treatment effect. </li></ul>Kastrati A., et al., ACC 2007 Oral Presentation. Conclusions I
  22. 22. <ul><li>Compared with Taxus stent, CYPHER ® stent is associated with: </li></ul><ul><ul><li>No significant difference in mortality </li></ul></ul><ul><ul><li>A significantly lower risk of stent thrombosis </li></ul></ul><ul><ul><li>A trend toward a lower combined risk of death or myocardial infarction </li></ul></ul><ul><ul><li>A significantly lower risk of death, myocardial infarction or reintervention </li></ul></ul>Kastrati A., et al., ACC 2007 Oral Presentation. Conclusions II

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