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

Drug-Eluting Stent Mortality Meta-AnalysisDrug-Eluting Stent Mortality Meta-AnalysisDrug-Eluting Stent Mortality Meta-AnalysisDrug-Eluting Stent Mortality Meta-Analysis

Presented atPresented at

European Society of Cardiology Scientific European Society of Cardiology Scientific Congress, September 2006Congress, September 2006

Presented by Dr. Alain J. NordmannPresented by Dr. Alain J. Nordmann

www. Clinical trial results.org

Bare Metal and Drug Eluting Stent in Same Pt:Bare Metal and Drug Eluting Stent in Same Pt:DES thrombosis, BMS stays openDES thrombosis, BMS stays open

Bare Metal and Drug Eluting Stent in Same Pt:Bare Metal and Drug Eluting Stent in Same Pt:DES thrombosis, BMS stays openDES 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: 1519–21McFadden EP et al, Lancet 2004; 364: 1519–21


Potential Magnitude of the Problem from a Public Health Potential Magnitude of the Problem from a Public Health PerspectivePerspective

Potential Magnitude of the Problem from a Public Health Potential Magnitude of the Problem from a Public Health PerspectivePerspective

•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 3.1% increase in the risk of death or MI with use of drug eluting stent vs bare metal stenteluting stent vs bare metal stent

•3.1% of 1,500,000 would be 4,500 death or MIs per year 3.1% of 1,500,000 would be 4,500 death or MIs per year associated with drug eluting stent use.associated with drug eluting stent use.

Wall Street Journal, By SYLVIA PAGÁN WESTPHAL and RON WINSLOW, September 7, 2006Wall Street Journal, By SYLVIA PAGÁN WESTPHAL and RON WINSLOW, September 7, 2006


Drug-Eluting Stent Mortality Meta-Analysis: BackgroundDrug-Eluting Stent Mortality Meta-Analysis: BackgroundDrug-Eluting Stent Mortality Meta-Analysis: BackgroundDrug-Eluting Stent Mortality Meta-Analysis: Background

• Compare mortality rates of patients treated with drug-Compare mortality rates of patients treated with drug-eluting stents (DES) versus bare-metal stents (BMS) eluting stents (DES) versus bare-metal stents (BMS) among randomized DES trialsamong randomized DES trials

• Compare mortality rates of different specific drug-eluting Compare mortality rates of different specific drug-eluting stents: sirolimus-eluting stents (SES) and paclitaxel-stents: sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES)eluting stents (PES)

• Compare mortality rates of patients treated with drug-Compare mortality rates of patients treated with drug-eluting stents (DES) versus bare-metal stents (BMS) eluting stents (DES) versus bare-metal stents (BMS) among randomized DES trialsamong randomized DES trials

• Compare mortality rates of different specific drug-eluting Compare mortality rates of different specific drug-eluting stents: sirolimus-eluting stents (SES) and paclitaxel-stents: sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES)eluting stents (PES)

Presented at ESC 2006Presented at ESC 2006


Drug-Eluting Stent Mortality Meta-Analysis: Study DesignDrug-Eluting Stent Mortality Meta-Analysis: Study DesignDrug-Eluting Stent Mortality Meta-Analysis: Study DesignDrug-Eluting Stent Mortality Meta-Analysis: Study Design


Primary Endpoint: Mortality (total, cardiac, and noncardiac)Primary Endpoint: Mortality (total, cardiac, and noncardiac) Primary Endpoint: Mortality (total, cardiac, and noncardiac)Primary Endpoint: Mortality (total, cardiac, and noncardiac)

Treatment with BMSTreatment with BMS Treatment with DES: SES or PESTreatment 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 lesionsMeta-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)Follow-up > 1 year post PCI (Mean follow-up = 3-4 years)


Drug-Eluting Stent Mortality Meta-Analysis: Total MortalityDrug-Eluting Stent Mortality Meta-Analysis: Total MortalityDrug-Eluting Stent Mortality Meta-Analysis: Total MortalityDrug-Eluting Stent Mortality Meta-Analysis: Total Mortality

•Total mortality did not differ at 1 year for BMS vs DES Total mortality did not differ at 1 year for BMS vs DES (OR 0.94, 95% CI 0.66-1.34) or for individual type of (OR 0.94, 95% CI 0.66-1.34) or for individual type of stent: SES (OR 0.86, 95% CI 0.49-1.51) and PES (OR stent: SES (OR 0.86, 95% CI 0.49-1.51) and PES (OR 0.98, 95% CI 0.64-1.48)0.98, 95% CI 0.64-1.48)

•Total mortality trended toward higher, but non-Total mortality trended toward higher, but non-significant, rates for DES vs BMS (OR 1.25, 95% CI significant, rates for DES vs BMS (OR 1.25, 95% CI 0.91-1.73) as well as for SES vs BMS (OR 1.48, 95% CI 0.91-1.73) as well as for SES vs BMS (OR 1.48, 95% CI 0.91-2.42) at 3 years0.91-2.42) at 3 years



Drug-Eluting Stent Mortality Meta-Analysis: Cardiac and Drug-Eluting Stent Mortality Meta-Analysis: Cardiac and Noncardiac MortalityNoncardiac Mortality

Drug-Eluting Stent Mortality Meta-Analysis: Cardiac and Drug-Eluting Stent Mortality Meta-Analysis: Cardiac and Noncardiac MortalityNoncardiac Mortality

•Cardiac mortality at 3 years did not differ with DES Cardiac mortality at 3 years did not differ with DES treatment vs BMS treatment (OR 1.00, 95% CI 0.62-treatment vs BMS treatment (OR 1.00, 95% CI 0.62-1.60)1.60)

•Non-cardiac mortality was directionally, but non-Non-cardiac mortality was directionally, but non-significantly, higher for treatment with DES vs BMS at 3 significantly, higher for treatment with DES vs BMS at 3 years (OR 1.45, 95% Cl 0.93-2.25)years (OR 1.45, 95% Cl 0.93-2.25)

•Treatment with SES was associated with significantly Treatment with SES was associated with significantly higher non-cardiac mortality at 2 years (OR 2.74, 95% CI higher non-cardiac mortality at 2 years (OR 2.74, 95% CI 1.22-6.13, p < 0.05) and 3 years (OR 2.04, 95% CI 1.00-1.22-6.13, p < 0.05) and 3 years (OR 2.04, 95% CI 1.00-4.15, p < 0.05) as compared with BMS4.15, p < 0.05) as compared with BMS



Drug-Eluting Stent Mortality Meta-Analysis: Mortality/MI in Drug-Eluting Stent Mortality Meta-Analysis: Mortality/MI in BASKET trialBASKET trial

Drug-Eluting Stent Mortality Meta-Analysis: Mortality/MI in Drug-Eluting Stent Mortality Meta-Analysis: Mortality/MI in BASKET trialBASKET trial


• BASKET trial BASKET trial demonstrated no demonstrated no significant difference significant difference in mortality and MI in mortality and MI outcomes at 18 outcomes at 18 months between months between treatment with BMS treatment with BMS and DES (7.5% vs and DES (7.5% vs 8.4%, p = 0.63) 8.4%, p = 0.63)

7.5%8.4%

0%

5%

10%

BMS DES

Death

/MI

7.5%8.4%

0%

5%

10%

BMS DES

Death

/MI

Death/MI in BMS vs DES patients (%) after 18 months Death/MI in BMS vs DES patients (%) after 18 months n = 826, p=0.63n = 826, p=0.63


Drug-Eluting Stent Mortality Meta-Analysis: Mortality in Drug-Eluting Stent Mortality Meta-Analysis: Mortality in RAVEL trialRAVEL trial

Drug-Eluting Stent Mortality Meta-Analysis: Mortality in Drug-Eluting Stent Mortality Meta-Analysis: Mortality in RAVEL trialRAVEL trial


• RAVEL trial RAVEL trial demonstrated no demonstrated no significant difference significant difference in mortality outcomes in mortality outcomes at 5 years between at 5 years between treatment with BMS treatment with BMS and SES (freedom and SES (freedom from death 92.9% vs from death 92.9% vs 87.9%, p = 0.26)87.9%, p = 0.26)

• Trends toward higher Trends toward higher total death in SES vs total death in SES vs BMS treatmentBMS treatment

92.9% 87.9%

0%

20%

40%

60%

80%

100%

BMS SES

Fre

edo

m f

rom

Dea

th

92.9% 87.9%

0%

20%

40%

60%

80%

100%

BMS SES

Fre

edo

m f

rom

Dea

th

Freedom from death in BMS vs SES patients (%) after 5 yearsFreedom from death in BMS vs SES patients (%) after 5 years p=0.26p=0.26


Drug-Eluting Stent Mortality Meta-AnalysisDrug-Eluting Stent Mortality Meta-Analysis: Limitations: LimitationsDrug-Eluting Stent Mortality Meta-AnalysisDrug-Eluting Stent Mortality Meta-Analysis: Limitations: Limitations

• The scope of this meta-analysis was limited in that The scope of this meta-analysis was limited in that none of the randomized trials were powered to none of the randomized trials were powered to investigate harder endpoints of death or Q-wave MIinvestigate harder endpoints of death or Q-wave MI

• Longer-term follow-up and greater insight into the Longer-term follow-up and greater insight into the specific causes of death will be usefulspecific causes of death will be useful

• The scope of this meta-analysis was limited in that The scope of this meta-analysis was limited in that none of the randomized trials were powered to none of the randomized trials were powered to investigate harder endpoints of death or Q-wave MIinvestigate harder endpoints of death or Q-wave MI

• Longer-term follow-up and greater insight into the Longer-term follow-up and greater insight into the specific causes of death will be usefulspecific causes of death will be useful



Drug-Eluting Stent Mortality Meta-Analysis: SummaryDrug-Eluting Stent Mortality Meta-Analysis: SummaryDrug-Eluting Stent Mortality Meta-Analysis: SummaryDrug-Eluting Stent Mortality Meta-Analysis: Summary

• Treatment with DES was not associated with a significant Treatment with DES was not associated with a significant difference in mortality as compared to treatment with BMS difference in mortality as compared to treatment with BMS at 3 yearsat 3 years

• Treatment with SES was associated with increased Treatment with SES was associated with increased noncardiac mortality at 3 years versus treatment with BMSnoncardiac mortality at 3 years versus treatment with BMS

• Present analysis suggests a potential, but nonsignificant, Present analysis suggests a potential, but nonsignificant, hazard in late mortality with DES as compared with BMShazard in late mortality with DES as compared with BMS

• Treatment with DES was not associated with a significant Treatment with DES was not associated with a significant difference in mortality as compared to treatment with BMS difference in mortality as compared to treatment with BMS at 3 yearsat 3 years

• Treatment with SES was associated with increased Treatment with SES was associated with increased noncardiac mortality at 3 years versus treatment with BMSnoncardiac mortality at 3 years versus treatment with BMS

• Present analysis suggests a potential, but nonsignificant, Present analysis suggests a potential, but nonsignificant, hazard in late mortality with DES as compared with BMShazard in late mortality with DES as compared with BMS


Documents

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