Drug-Eluting Stent Mortality Meta-Analysis Presented at European Society of Cardiology Scientific Congress, September 2006 Presented by Dr. Alain J. Nordmann

www. Clinical trial results.org Bare Metal and Drug Eluting Stent in Same Pt: DES thrombosis, BMS stays open “We report four cases of angiographically-confirmed stent thrombosis that occurred late after elective implantation of polymer-based paxlitaxel-eluting (343 and 442 days) or sirolimuseluting (335 and 375 days) stents, and resulted in myocardial infarction. All cases arose soon after antiplatelet therapy was interrupted. If confirmed in systematic long-term follow-up studies, our findings have potentially serious clinical implications.” “We report four cases of angiographically-confirmed stent thrombosis that occurred late after elective implantation of polymer-based paxlitaxel-eluting (343 and 442 days) or sirolimuseluting (335 and 375 days) stents, and resulted in myocardial infarction. All cases arose soon after antiplatelet therapy was interrupted. If confirmed in systematic long-term follow-up studies, our findings have potentially serious clinical implications.” McFadden EP et al, Lancet 2004; 364: 1519–21

www. Clinical trial results.org Potential Magnitude of the Problem from a Public Health Perspective 1,500,000 stents placed per year in the US1,500,000 stents placed per year in the US 3.1% increase in the risk of death or MI with use of drug eluting stent vs bare metal stent3.1% increase in the risk of death or MI with use of drug eluting stent vs bare metal stent 3.1% of 1,500,000 would be 4,500 death or MIs per year associated with drug eluting stent use.3.1% of 1,500,000 would be 4,500 death or MIs per year associated with drug eluting stent use. Wall Street Journal, By SYLVIA PAGÁN WESTPHAL and RON WINSLOW, September 7, 2006

www. Clinical trial results.org Drug-Eluting Stent Mortality Meta-Analysis: Background Compare mortality rates of patients treated with drug- eluting stents (DES) versus bare-metal stents (BMS) among randomized DES trialsCompare mortality rates of patients treated with drug- eluting stents (DES) versus bare-metal stents (BMS) among randomized DES trials Compare mortality rates of different specific drug-eluting stents: sirolimus-eluting stents (SES) and paclitaxel- eluting stents (PES)Compare mortality rates of different specific drug-eluting stents: sirolimus-eluting stents (SES) and paclitaxel- eluting stents (PES) Compare mortality rates of patients treated with drug- eluting stents (DES) versus bare-metal stents (BMS) among randomized DES trialsCompare mortality rates of patients treated with drug- eluting stents (DES) versus bare-metal stents (BMS) among randomized DES trials Compare mortality rates of different specific drug-eluting stents: sirolimus-eluting stents (SES) and paclitaxel- eluting stents (PES)Compare mortality rates of different specific drug-eluting stents: sirolimus-eluting stents (SES) and paclitaxel- eluting stents (PES) Presented at ESC 2006

www. Clinical trial results.org Drug-Eluting Stent Mortality Meta-Analysis: Study Design Presented at ESC 2006  Primary Endpoint: Mortality (total, cardiac, and noncardiac) Treatment with BMS Treatment with DES: SES or PES Meta-analysis of 17 randomized trials of treatment with DES versus BMS in patients undergoing percutaneous coronary intervention (PCI) for de novo coronary lesions Follow-up > 1 year post PCI (Mean follow-up = 3-4 years)

www. Clinical trial results.org Drug-Eluting Stent Mortality Meta-Analysis: Total Mortality Total mortality did not differ at 1 year for BMS vs DES (OR 0.94, 95% CI ) or for individual type of stent: SES (OR 0.86, 95% CI ) and PES (OR 0.98, 95% CI )Total mortality did not differ at 1 year for BMS vs DES (OR 0.94, 95% CI ) or for individual type of stent: SES (OR 0.86, 95% CI ) and PES (OR 0.98, 95% CI ) Total mortality trended toward higher, but non- significant, rates for DES vs BMS (OR 1.25, 95% CI ) as well as for SES vs BMS (OR 1.48, 95% CI ) at 3 yearsTotal mortality trended toward higher, but non- significant, rates for DES vs BMS (OR 1.25, 95% CI ) as well as for SES vs BMS (OR 1.48, 95% CI ) at 3 years Presented at ESC 2006

www. Clinical trial results.org Drug-Eluting Stent Mortality Meta-Analysis: Cardiac and Noncardiac Mortality Cardiac mortality at 3 years did not differ with DES treatment vs BMS treatment (OR 1.00, 95% CI )Cardiac mortality at 3 years did not differ with DES treatment vs BMS treatment (OR 1.00, 95% CI ) Non-cardiac mortality was directionally, but non- significantly, higher for treatment with DES vs BMS at 3 years (OR 1.45, 95% Cl )Non-cardiac mortality was directionally, but non- significantly, higher for treatment with DES vs BMS at 3 years (OR 1.45, 95% Cl ) Treatment with SES was associated with significantly higher non-cardiac mortality at 2 years (OR 2.74, 95% CI , p < 0.05) and 3 years (OR 2.04, 95% CI , p < 0.05) as compared with BMSTreatment with SES was associated with significantly higher non-cardiac mortality at 2 years (OR 2.74, 95% CI , p < 0.05) and 3 years (OR 2.04, 95% CI , p < 0.05) as compared with BMS Presented at ESC 2006

www. Clinical trial results.org Drug-Eluting Stent Mortality Meta-Analysis: Mortality/MI in BASKET trial Drug-Eluting Stent Mortality Meta-Analysis: Mortality/MI in BASKET trial Presented at ESC 2006 BASKET trial demonstrated no significant difference in mortality and MI outcomes at 18 months between treatment with BMS and DES (7.5% vs 8.4%, p = 0.63)BASKET trial demonstrated no significant difference in mortality and MI outcomes at 18 months between treatment with BMS and DES (7.5% vs 8.4%, p = 0.63) Death/MI in BMS vs DES patients (%) after 18 months n = 826, p=0.63

www. Clinical trial results.org Drug-Eluting Stent Mortality Meta-Analysis: Mortality in RAVEL trial Drug-Eluting Stent Mortality Meta-Analysis: Mortality in RAVEL trial Presented at ESC 2006 RAVEL trial demonstrated no significant difference in mortality outcomes at 5 years between treatment with BMS and SES (freedom from death 92.9% vs 87.9%, p = 0.26)RAVEL trial demonstrated no significant difference in mortality outcomes at 5 years between treatment with BMS and SES (freedom from death 92.9% vs 87.9%, p = 0.26) Trends toward higher total death in SES vs BMS treatmentTrends toward higher total death in SES vs BMS treatment Freedom from death in BMS vs SES patients (%) after 5 years p=0.26 p=0.26

www. Clinical trial results.org Drug-Eluting Stent Mortality Meta-Analysis : Limitations The scope of this meta-analysis was limited in that none of the randomized trials were powered to investigate harder endpoints of death or Q-wave MIThe scope of this meta-analysis was limited in that none of the randomized trials were powered to investigate harder endpoints of death or Q-wave MI Longer-term follow-up and greater insight into the specific causes of death will be usefulLonger-term follow-up and greater insight into the specific causes of death will be useful The scope of this meta-analysis was limited in that none of the randomized trials were powered to investigate harder endpoints of death or Q-wave MIThe scope of this meta-analysis was limited in that none of the randomized trials were powered to investigate harder endpoints of death or Q-wave MI Longer-term follow-up and greater insight into the specific causes of death will be usefulLonger-term follow-up and greater insight into the specific causes of death will be useful Presented at ESC 2006

www. Clinical trial results.org Drug-Eluting Stent Mortality Meta-Analysis: Summary Treatment with DES was not associated with a significant difference in mortality as compared to treatment with BMS at 3 yearsTreatment with DES was not associated with a significant difference in mortality as compared to treatment with BMS at 3 years Treatment with SES was associated with increased noncardiac mortality at 3 years versus treatment with BMSTreatment with SES was associated with increased noncardiac mortality at 3 years versus treatment with BMS Present analysis suggests a potential, but nonsignificant, hazard in late mortality with DES as compared with BMSPresent analysis suggests a potential, but nonsignificant, hazard in late mortality with DES as compared with BMS Treatment with DES was not associated with a significant difference in mortality as compared to treatment with BMS at 3 yearsTreatment with DES was not associated with a significant difference in mortality as compared to treatment with BMS at 3 years Treatment with SES was associated with increased noncardiac mortality at 3 years versus treatment with BMSTreatment with SES was associated with increased noncardiac mortality at 3 years versus treatment with BMS Present analysis suggests a potential, but nonsignificant, hazard in late mortality with DES as compared with BMSPresent analysis suggests a potential, but nonsignificant, hazard in late mortality with DES as compared with BMS Presented at ESC 2006