1. Coronary Stenting: Drug-eluting vs Bare-metal Natalie Cleaver, PA-S Lock Haven University PA Program Evidence Based Medicine February 26, 2009

2. Coronary Artery Disease (CAD)  #1 cause of death in the US  10% of office visits  8% ER visits

3. Percutaneous Coronary Intervention (PCI)  Coronary angioplasty, Angioplasty, PTCA  1,000,000+ PCI procedures performed yearly in the US  Primary vs Elective  ‘door-to-balloon time’ <90 minutes<90 minutes

4. Coronary Stenting  Predominant form of PCI  Used in >90% PCI procedures worldwide  Bare-metal or drug- eluting stents  Use of dual anti- platelet therapy (DAT) following stent placement ASAASA clopidigrel (Plavix) or ticlopidine (Ticlid)clopidigrel (Plavix) or ticlopidine (Ticlid)

5. Before Stenting http://www.jeffersonhospital.org/kit/heartcare/article14488.html

6. After Stenting http://www.jeffersonhospital.org/kit/heartcare/article14488.html

7. Bare-metal Stents (BMS)  1987 – first use of stents in humans  Stainless steel or cobalt-chromium alloy  Require DAT for minimum of 3 months ASA indefinitelyASA indefinitely

8. Drug-eluting Stents (DES)  “coated” or “medicated” stent  Different types Sirolimus-eluting, CYPHERSirolimus-eluting, CYPHER (FDA approved April 2003) (FDA approved April 2003) Paclitaxel-eluting, TAXUSPaclitaxel-eluting, TAXUS (FDA approved March 2004) (FDA approved March 2004) Zotarolimus-eluting, EndeavorZotarolimus-eluting, Endeavor (FDA approved February 2008) (FDA approved February 2008) Several 2 nd & 3 rd generation stents in researchSeveral 2 nd & 3 rd generation stents in research  Require DAT for minimum 1 year ASA indefinitelyASA indefinitely

9. Drug-eluting Stents  2005 sampling of 140 US hospitals 94% of patients treated with coronary stents received at least one DES94% of patients treated with coronary stents received at least one DES  Recent concern about stent thrombosis, mandated dual- antiplatelet therapy DES use declined to 60-70%DES use declined to 60-70%

10. Considerations for Stent Selection  Compliance with DAT Access, cost, managementAccess, cost, management  Bleeding risk Upcoming non-cardiac surgery, GIB, etcUpcoming non-cardiac surgery, GIB, etc  Cost Drug-eluting > bare-metalDrug-eluting > bare-metal  Co-morbidities DM – higher risk for re-stenosisDM – higher risk for re-stenosis

11. Evidence Based Medicine  PICO Question In adult patients requiring coronary stenting, do drug-eluting stents result in reduced mortality rates and reduced need for repeat revascularization procedures, as compared to bare-metal stents?In adult patients requiring coronary stenting, do drug-eluting stents result in reduced mortality rates and reduced need for repeat revascularization procedures, as compared to bare-metal stents?

12. Kastrati et al. (2007)  Analysis of 14 randomized trials Individual data on 4,958 patientsIndividual data on 4,958 patients  Sirolimus-eluting vs bare-metal  Findings: No difference in mortality (5-year period)No difference in mortality (5-year period) Overall risk of death similarOverall risk of death similar Combined risk of death and MI similarCombined risk of death and MI similar No significant difference in overall risk of stent thrombosisNo significant difference in overall risk of stent thrombosis  Slight increase assoc. with SES after 1 year

13. Kastrati et al. (2007)  However… Significant reduction in combined risk of death/MI/ re-interventionSignificant reduction in combined risk of death/MI/ re-intervention Hazard Ratio Overall risk of death 1.03 Combined risk of death and MI 0.97 Combined risk of death, MI, and re-intervention 0.43 Overall risk of stent thrombosis 1.09

14. Malenka et al. (2008)  Observational study of 38,917 Medicare patients Eras before/after DES availabilityEras before/after DES availability  Findings: DES had lower 2-year risk for repeat PCI, lower 2-year risk for CABGDES had lower 2-year risk for repeat PCI, lower 2-year risk for CABG After risk adjustment: repeat PCI still significant (HR 0.82), death/STEMI similar (HR 0.96)After risk adjustment: repeat PCI still significant (HR 0.82), death/STEMI similar (HR 0.96)

15. Malenka et al. (2008) Figure A. 2-year risks for repeat PCI and CABG 2-year Risks for Repeat Percutaneous Coronary Intervention and Coronary Artery Bypass Surgery

16. Mauri et al. (2008)  Observational study of 7,217 PCI patients with acute MI  Findings: 2-year risk adjusted mortality rates for all MIs were lower for DES2-year risk adjusted mortality rates for all MIs were lower for DES Also true for both STEMI and NSTEMIAlso true for both STEMI and NSTEMI 2-year rate of repeat revascularization significantly lower for DES2-year rate of repeat revascularization significantly lower for DES

17. Mauri et al. (2008) Figure B. 2-year risk adjusted rates for all MIs, STEMIs, Non STEMIs, and repeat revascularization procedures (PCI or CABG)

18. Shishehbor et al. (2008)  Observational study of 8,032 patients, all-cause mortality  Findings: All-cause mortality significant lower with DES, both unadjusted/adjusted Cox proportional modelsAll-cause mortality significant lower with DES, both unadjusted/adjusted Cox proportional models  HR 0.62, P<0.001 Also lower mortality with DES using propensity-matched groupingAlso lower mortality with DES using propensity-matched grouping  HR 0.54, P<0.001

19. Shishehbor et al. (2008)  Use of DES assoc. with decrease in RR for all-cause mortality 38%

20. Stettler et al. (2007)  Meta-analysis of 38 RCT (138,023 patients) with signs/symptoms of myocardial ischemia d/t CAD  Drug-eluting vs bare-metal, or sirolimus- eluting vs paclitaxel-eluting  Findings: Mortality similar among three comparison groupsMortality similar among three comparison groups  SES vs BMS: HR 1.00  PES vs BMS: HR 1.03  SES vs PES: HR 0.96

21. Stettler et al. (2007)  SES assoc. with lowest risk of MI  DES significantly lowered target lesion revascularization, SES > PES Risk of MI HRP-value SES vs BMS0.810.030 SES vs PES0.830.045 Target Lesion Revascularization HRP-value SES vs BMS0.30<0.001 PES vs BMS0.42<0.001 SES vs PES0.700.0021

22. Evidence Based Medicine  Another look at the PICO question… In adult patients requiring coronary stenting, do drug-eluting stents result in reduced mortality rates and reduced need for repeat revascularization procedures, as compared to bare-metal stents?In adult patients requiring coronary stenting, do drug-eluting stents result in reduced mortality rates and reduced need for repeat revascularization procedures, as compared to bare-metal stents?

23. Conclusions  Drug-eluting stents associated with reduced need for repeat revascularization procedures

24. Conclusions  What about mortality rates??? Not significantly different in randomized trials and meta-analyses Some observational studies show reduction with DES

25. Bibliography  Kastrati, A., Mehilli, J., Pache, J., Kaiser, C., Valgimigli, M., Kelbaek, H., et al. (2007). Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents. The New England Journal of Medicine. 356, 1030-39.  Malenka, D. J., Kaplan, A. V., Lucas, F. L., Sharp, S. M., & Skinner, J. S. (2008). Outcomes following coronary stenting in the era of bare-metal vs the era of drug-eluting stents. Journal of the American Medical Association. 299, 2868-76.  Mauri, L., Silbaugh, T. S., Garg, P., Wolf, R. E., Zelevinsky, K., Lovett, A., et al. (2008). Drug-eluting or bare-metal stents for acute myocardial infarction. New England Journal of Medicine. 359, 1330-42.  Shishehbor, M. H., Goel, S. S., Kapadia, S. R., Bhatt, D. L., Kelly, P., Raymond, R. E., et al. (2008). Long-term impact of drug-eluting stents versus bare-metal stents on all-cause mortality. Journal of the American College of Cardiology. 52, 1041-48.  Stettler, C., Wandel, S., Allemann, S., Kastrati, A., Morice, M. C., Schomig, A., et al. (2007). Outcomes associated with drug-eluting and bare-metal stents: A collaborative network meta-analysis. Lancet. 370, 937-48.

26. Additional References  King, S.B., Smith, S.C., Hirshfeld, J.W., Jacobs, A.K., Morrison, D.A., & Williams, D.O. (2008). 2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention. Journal of American College of Cardiology. 51, 172-207.  www.acc.org/qualityandscience/clinical www.acc.org/qualityandscience/clinical  www.pcta.org www.pcta.org  www.americanheart.org www.americanheart.org  www.nhlbi.nih.gov www.nhlbi.nih.gov

27. Questions