Coronary Stenting: Coronary Stenting: Drug-eluting vs Bare-metalDrug-eluting vs Bare-metal

Natalie Cleaver, PA-SNatalie Cleaver, PA-SLock Haven University PA ProgramLock Haven University PA Program

Evidence Based MedicineEvidence Based MedicineFebruary 26, 2009February 26, 2009

Coronary Artery Disease (CAD)Coronary Artery Disease (CAD)

#1 cause of death in #1 cause of death in the USthe US

10% of office visits10% of office visits

8% ER visits8% ER visits

Percutaneous Coronary Percutaneous Coronary Intervention (PCI)Intervention (PCI)

Coronary angioplasty, Angioplasty, Coronary angioplasty, Angioplasty, PTCAPTCA

1,000,000+ PCI procedures 1,000,000+ PCI procedures performed yearly in the USperformed yearly in the US

Primary vs ElectivePrimary vs Elective ‘‘door-to-balloon time’door-to-balloon time’

• <90 minutes<90 minutes

Coronary StentingCoronary Stenting Predominant form of Predominant form of

PCIPCI Used in >90% PCI Used in >90% PCI

procedures worldwideprocedures worldwide Bare-metal or drug-Bare-metal or drug-

eluting stentseluting stents Use of dual anti-Use of dual anti-

platelet therapy (DAT) platelet therapy (DAT) following stent following stent placementplacement• ASA ASA • clopidigrel (Plavix) or clopidigrel (Plavix) or

ticlopidine (Ticlid)ticlopidine (Ticlid)

Before StentingBefore Stenting

http://www.jeffersonhospital.org/kit/heartcare/article14488.html

After StentingAfter Stenting

http://www.jeffersonhospital.org/kit/heartcare/article14488.html

Bare-metal Stents (BMS)Bare-metal Stents (BMS)

1987 – first use of 1987 – first use of stents in humansstents in humans

Stainless steel or Stainless steel or cobalt-chromium alloycobalt-chromium alloy

Require DAT for Require DAT for minimum of 3 monthsminimum of 3 months• ASA indefinitelyASA indefinitely

Drug-eluting Stents (DES)Drug-eluting Stents (DES) ““coated” or “medicated” stentcoated” or “medicated” stent

Different typesDifferent types• Sirolimus-elutingSirolimus-eluting, CYPHER , CYPHER (FDA approved April 2003)(FDA approved April 2003)• Paclitaxel-elutingPaclitaxel-eluting, TAXUS , TAXUS (FDA approved March 2004)(FDA approved March 2004)• Zotarolimus-elutingZotarolimus-eluting, Endeavor , Endeavor (FDA approved February 2008)(FDA approved February 2008)• Several 2Several 2ndnd & 3 & 3rdrd generation stents in research generation stents in research

Require DAT for minimum 1 yearRequire DAT for minimum 1 year• ASA indefinitelyASA indefinitely

Drug-eluting StentsDrug-eluting Stents

2005 sampling of 140 US hospitals2005 sampling of 140 US hospitals• 94% of patients treated with coronary 94% of patients treated with coronary

stents received at least one DESstents received at least one DES Recent concern about stent Recent concern about stent

thrombosis, mandated dual-thrombosis, mandated dual-antiplatelet therapy antiplatelet therapy • DES use declined to 60-70%DES use declined to 60-70%

Considerations for Stent SelectionConsiderations for Stent Selection

Compliance with DATCompliance with DAT• Access, cost, managementAccess, cost, management

Bleeding riskBleeding risk• Upcoming non-cardiac surgery, GIB, etcUpcoming non-cardiac surgery, GIB, etc

CostCost• Drug-eluting > bare-metalDrug-eluting > bare-metal

Co-morbiditiesCo-morbidities• DM – higher risk for re-stenosisDM – higher risk for re-stenosis

Evidence Based MedicineEvidence Based Medicine

PICO QuestionPICO Question

• In adult patients requiring coronary In adult patients requiring coronary stenting, do drug-eluting stents result in stenting, do drug-eluting stents result in reduced mortality rates and reduced reduced mortality rates and reduced need for repeat revascularization need for repeat revascularization procedures, as compared to bare-metal procedures, as compared to bare-metal stents?stents?

Kastrati et al. (2007)Kastrati et al. (2007)

Analysis of 14 randomized trialsAnalysis of 14 randomized trials• Individual data on 4,958 patientsIndividual data on 4,958 patients

Sirolimus-eluting vs bare-metalSirolimus-eluting vs bare-metal Findings: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 No significant difference in overall risk of

stent thrombosisstent thrombosis Slight increase assoc. with SES after 1 yearSlight increase assoc. with SES after 1 year

Kastrati et al. (2007)Kastrati et al. (2007)

However…However…• Significant Significant

reduction in reduction in combined risk of combined risk of death/MI/ death/MI/ re-re-interventionintervention

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

Malenka et al. (2008)Malenka et al. (2008)

Observational study of 38,917 Observational study of 38,917 Medicare patientsMedicare patients• Eras before/after DES availabilityEras before/after DES availability

Findings:Findings:• DES had lower 2-year risk for repeat PCI, DES had lower 2-year risk for repeat PCI,

lower 2-year risk for CABGlower 2-year risk for CABG• After risk adjustment: repeat PCI still After risk adjustment: repeat PCI still

significant (HR 0.82), death/STEMI significant (HR 0.82), death/STEMI similar (HR 0.96)similar (HR 0.96)

Malenka et al. (2008)Malenka et al. (2008)

17.1

2.7

20.0

4.2

0

5

10

15

20

25

Repeat PCI (P<0.001) CABG (P<0.01)

2-Y

ear

Ris

k %

DES BMS

Figure A. 2-year risks for repeat PCI and CABG

2-year Risks for Repeat Percutaneous Coronary Intervention and Coronary Artery Bypass Surgery

Mauri et al. (2008)Mauri et al. (2008)

Observational study of 7,217 PCI Observational study of 7,217 PCI patients with acute MIpatients with acute MI

Findings:Findings:• 2-year risk adjusted mortality rates for 2-year risk adjusted mortality rates for

all MIs were lower for DESall MIs were lower for DES• Also true for both STEMI and NSTEMIAlso true for both STEMI and NSTEMI• 2-year rate of repeat revascularization 2-year rate of repeat revascularization

significantly lower for DESsignificantly lower for DES

Mauri et al. (2008)Mauri et al. (2008)2-year Risk Adjusted Rates for All MIs, ST-elevation MIs, Non ST-

elevation MIs, and Repeat Revascularization Procedures

10.2

8.5

12.8

9.6

12.8

11.6

15.614.5

0

2

4

6

8

10

12

14

16

18

All MI (P=0.02) STEMI (P=0.008) NSTEMI (P=0.04) RepeatRevascularization

(P<0.001)

Ris

k %

DES

BMS

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

Shishehbor et al. (2008)Shishehbor et al. (2008)

Observational study of 8,032 Observational study of 8,032 patients, all-cause mortalitypatients, all-cause mortality

Findings:Findings:• All-cause mortality significant lower with All-cause mortality significant lower with

DES, both unadjusted/adjusted Cox DES, both unadjusted/adjusted Cox proportional modelsproportional models

HR 0.62, P<0.001HR 0.62, P<0.001

• Also lower mortality with DES using Also lower mortality with DES using propensity-matched groupingpropensity-matched grouping

HR 0.54, P<0.001HR 0.54, P<0.001

Shishehbor et al. (2008)Shishehbor et al. (2008)

Use of DES Use of DES assoc. with assoc. with decrease in decrease in RR for all-RR for all-cause cause mortalitymortality

38%

Stettler et al. (2007)Stettler et al. (2007)

Meta-analysis of 38 RCT (138,023 Meta-analysis of 38 RCT (138,023 patients) with signs/symptoms of patients) with signs/symptoms of myocardial ischemia d/t CADmyocardial ischemia d/t CAD

Drug-eluting vs bare-metal, or sirolimus-Drug-eluting vs bare-metal, or sirolimus-eluting vs paclitaxel-elutingeluting vs paclitaxel-eluting

Findings:Findings:• Mortality similar among three comparison Mortality similar among three comparison

groupsgroups SES vs BMS: HR 1.00SES vs BMS: HR 1.00 PES vs BMS: HR 1.03PES vs BMS: HR 1.03 SES vs PES: HR 0.96SES vs PES: HR 0.96

Stettler et al. (2007)Stettler et al. (2007)

SES assoc. with lowest risk of MISES assoc. with lowest risk of MI

DES significantly lowered target lesion DES significantly lowered target lesion revascularization, SES > PESrevascularization, SES > PES

Risk of MI HR P-value

SES vs BMS 0.81 0.030

SES vs PES 0.83 0.045

Target Lesion Revascularization

HR P-value

SES vs BMS 0.30 <0.001

PES vs BMS 0.42 <0.001

SES vs PES 0.70 0.0021

Evidence Based MedicineEvidence Based Medicine

Another look at the PICO question…Another look at the PICO question…

• In adult patients requiring coronary In adult patients requiring coronary stenting, do drug-eluting stents result in stenting, do drug-eluting stents result in reduced mortality rates and reduced reduced mortality rates and reduced need for repeat revascularization need for repeat revascularization procedures, as compared to bare-metal procedures, as compared to bare-metal stents?stents?

ConclusionsConclusions Drug-eluting stents associated with Drug-eluting stents associated with

reduced need for repeat reduced need for repeat revascularization proceduresrevascularization procedures

ConclusionsConclusions

What about What about mortality rates???mortality rates???• Not significantly Not significantly

different in different in randomized trials randomized trials and meta-analysesand meta-analyses

• Some observational Some observational studies show studies show reduction with DESreduction with DES

BibliographyBibliography Kastrati, A., Mehilli, J., Pache, J., Kaiser, C., Valgimigli, M., Kastrati, A., Mehilli, J., Pache, J., Kaiser, C., Valgimigli, M.,

Kelbaek, H., et al. Kelbaek, H., et al. (2007). Analysis of 14 trials comparing (2007). Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents. sirolimus-eluting stents with bare-metal stents. The New England The New England Journal of MedicineJournal of Medicine. 356, 1030-39.. 356, 1030-39.

Malenka, D. J., Kaplan, A. V., Lucas, F. L., Sharp, S. M., & Skinner, Malenka, D. J., Kaplan, A. V., Lucas, F. L., Sharp, S. M., & Skinner, J. S. (2008). Outcomes following coronary stenting in the era of J. S. (2008). Outcomes following coronary stenting in the era of bare-metal vs the era of drug-eluting stents. bare-metal vs the era of drug-eluting stents. Journal of the Journal of the American Medical Association. American Medical Association. 299, 2868-76.299, 2868-76.

Mauri, L., Silbaugh, T. S., Garg, P., Wolf, R. E., Zelevinsky, K., Mauri, L., Silbaugh, T. S., Garg, P., Wolf, R. E., Zelevinsky, K., Lovett, A., et al. (2008). Drug-eluting or bare-metal stents for Lovett, A., et al. (2008). Drug-eluting or bare-metal stents for acute myocardial infarction. acute myocardial infarction. New England Journal of Medicine. New England Journal of Medicine. 359, 1330-42.359, 1330-42.

Shishehbor, M. H., Goel, S. S., Kapadia, S. R., Bhatt, D. L., Kelly, 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 P., Raymond, R. E., et al. (2008). Long-term impact of drug-eluting stents versus bare-metal stents on all-cause mortality. stents versus bare-metal stents on all-cause mortality. Journal of Journal of the American College of Cardiology. the American College of Cardiology. 52, 1041-48.52, 1041-48.

Stettler, C., Wandel, S., Allemann, S., Kastrati, A., Morice, M. C., Stettler, C., Wandel, S., Allemann, S., Kastrati, A., Morice, M. C., Schomig, A., et al. Schomig, A., et al. (2007). Outcomes associated with drug-eluting (2007). Outcomes associated with drug-eluting and bare-metal stents: A collaborative network meta-analysis. and bare-metal stents: A collaborative network meta-analysis. Lancet. Lancet. 370, 937-48.370, 937-48.

Additional ReferencesAdditional References King, S.B., Smith, S.C., Hirshfeld, J.W., Jacobs, A.K., King, S.B., Smith, S.C., Hirshfeld, J.W., Jacobs, A.K.,

Morrison, D.A., & Williams, D.O. (2008). 2007 Focused Morrison, D.A., & Williams, D.O. (2008). 2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention. Percutaneous Coronary Intervention. Journal of American Journal of American College of Cardiology. College of Cardiology. 51, 172-207.51, 172-207.

www.acc.org/qualityandscience/clinical www.acc.org/qualityandscience/clinical www.pcta.orgwww.pcta.org www.americanheart.orgwww.americanheart.org www.nhlbi.nih.govwww.nhlbi.nih.gov

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