Drug Eluting VS Bare Metal Stents

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Drug Eluting VS Bare Metal Stents

• Dr. Prateek Suri

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Part 1

• History
• Restenosis
• Bms vs poba
• Types of DES
• Restenosis results
• Over all trial results

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Part 2

• Overall trial results
• Registry data
• Controversies
• On vs off-label use
• Differences between DES brands
• Early vs late results
• Antiplatelet treatment

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Evolution of PCI

• 1977 Balloon Angioplasty (POBA)
• 1994 Bare Metal Stent (BMS)
• 2003 Drug Eluting Stent (DES)

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Coronary Angioplasty (PTCA) Andreas Gruntzig
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Coronary StentingJulio Palmaz
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PCI Procedural refinements Stents
Expandable metal mesh tubes that buttresses the
dilated segment, limit restenosis. Drug eluting
stents further reduce cellular proliferation in
response to the injury of dilatation.
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Restenosis

• Elastic recoil after balloon deflation, the
  large number of elastic fibers in the tunica
  media cause a mechanical collapse.
• Neointimal proliferation (NI) formation of an
  inner layer at the site of injury, composed of
  cells and ECM on the intimal surface
• Negative remodeling constriction of the vessel
  by the formation of a fibrotic scar within the
  adventitia.

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Comparing PTCA and BMS
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Acute stent-induced damage to the plaque
Fibrous cap
Necrotic core
Intima
Media
Adventitia
ANGIOPLASTY / STENT INSERTION
Embolisation of necrotic core
Intimal and medial tears
Thrombosis
Endothelial loss
Longitudinal translocation of plaque
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Processes needed to heal the plaque

• Re-endothelialisation
• Resolution of inflammation
• Thrombus reorganisation
• Smooth muscle cell proliferation
• Smooth muscle cell matrix synthesis
• Return of vasomotor regulation

Foreign body reaction due to polymers -giant
cell inflammation
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Current Drug eluting stents

• Cypher- Sirolimus(2003)
• Taxus- Paclitaxel(2004)
• Endeavor Zotarilimus(2008)
• Xience V /Promus Everolimus(2008)

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Meta analyses Lancet SEP 2007 38 TRIALS comparing
DES with BMS

• 768 DEATHS (232/4921 BMS)
• (263/6331-PES)
• (273/6771-SES)
• 850 cases of myocardial infarction
• ( 256/4891-BMS)
• (319/6300- PES)
• (275/6771-SES)
• 1926 CASES OF TLR(905/4763 BMS)
• (567/6328PES)
• (454/6621
  SES)
• 188 CASES OF STENT THROMBOSIS
  (50/4003 BMS)
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  (72/4327 PES)
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  (66/4643 SES)
• 
  

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Lancet september 2007meta analyses of 38 trials
summary

• Similar rates of overall and cardiac mortality
• Marked reduction in target lesion
  revascularisation with DES
• Use of sirolimus eluting stents is associated
  with a reduction in risk of myocardial
  infarction.
• Risk of late stent thrombosis is doubled in PES
  compared to both BMS /SES

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• End of part 1
• Come back next week!

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DES indications

• On label
• Single de novo lesion in a native coronary artery
  in patients with stable CAD
• Cypher reference vessel diameter (RVD) 2.5-3.5
  mm, length 30 mm
• Taxus RVD 2.5-3.75 mm, length 28 mm
• Endeavor RVD 2.5-3.5 mm, length 27 mm
• Xience V/Promus RVD 2.5-4.25 mm, length 28 mm.
• Off-label
• Everything else very long or very small lesions,
  bifurcations, CTOs, ISR, left main disease,
  multiple lesion or vessels, SVG, AMI

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Qusestions regarding SAFETY 2005/6

• Swedish SCAAR study
• Bavry meta analyses
• Camenzind meta analyses
• Nordmann meta analyses

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OUTCOMES

• 3887 events occurred during the course of this
  study including 2463 myocardial infarctions
  (1713-BMS and 750 DES) and 1424 deaths (999 BMS
  and 425 DES)
• At 6 months event rate in DES was lower than BMS
  but after 6 months patients with DES had a
  significantly higher event rate.
• At 3 years mortality significantly higher in
  patients with DES (RR 1.18)and from 6 months to 1
  year RR for DEATH was 1.32 in DES.

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Off-label/Real-world DES outcomeSwedish PCI
Registry

• 13,738 BMS 6033 DES implanted in 2003-2004
• Complete long-term f/up from National registry of
  MI, CABG, and death
• DES use in Sweden 62 ? 26 from Jan 06 to Oct 06

Absolute excess mortality 0.3
Wallentin. FDA Hearing 12/06
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Net Safety Outcome
Does the Benefit Outweigh the Risk?
Benefit
Risk
Stent thrombosis
Reduced restenosis
Death or Myocardial Infarction
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CREDO trial (LANCET 2002 NOV)

• Assessed the advantage of 12 month clopidogrel in
  patients with PCI
• 1053 patients received clopidogrel and 1063
  placebo 28 days after PCI and continued for 12
  months.

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Long-term Benefits of Clopidogrel in PCI Patients
1 year results
(MI, Stroke, or Death)
11.5
27 RRR p 0.02
Standard therapy including ASA JAMA, November
20, 2002 Vol 288, No 19 2411 2420
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Overall Safety Outcomes Conclusions

• No fatal bleeds or intracranial hemorrhages were
  observed
• When Clopidogrel was continued for a full year
  there was no statistically significant increase
  in major bleeding (8.8 vs. 6.7 , p0.07), and
  minor bleedings rates were approximately equal
• Approximately 2/3 of all major bleeds occurred in
  patients undergoing CABG
• CABG patients in both groups expericed a high
  incidence of major bleeds

JAMA, November 20, 2002 Vol 288, No 19 2411
2420
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Cure trial (NEJM 2001)

• Addition of clopidogrel to aspirin in patients
  with ACS continued for 12 months.
• 12562 patients out of which 6529 received
  clopidogrel and 6303 placebo

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Cost of dual antiplatelet therapy after DES

• 800- Bare metal stents
• 2400- Drug eluting stents cost of dual
  antiplatelet therapyrisk of bleeding

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SCAAR STUDY GROUP NEJM MAY 2009

• Compared the outcome in 10294 patients who
  received one drug eluting stent with 18659
  patients who received a bare metal stent
  registered between 2003 and 2006 and followed up
  for 1-5 years
• It also compared total cohort of 19681 patients
  who received at least 1 drug eluting stent and
  28286 patients who received one or more bare meta
  stents .

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Outcomes

• 2044/18659 had MI in bare metal stent group and
  1154/10294 in drug eluting group
• 1616 deaths/18659 in bare metal stent compared to
  764/10294 in drug eluting group
• In the total cohort 5565 patients had MI
  (3295-BMS and 2723 DES) and 4247 deaths (2706
  BMS and 1541 DES)
• During the first 6 months event rate was lower
  for DES but this was offset by a higher event
  rate thereafter.
• Average rate of restenosis was 3 events
  /100patient years in DES compared to 4.7 for bare
  metal stents giving a NNT 39

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SCAAR study is back May 2009 NEJM KEY POINTS

• Similar risks of death and myocardial infarction
  observed in people receiving bare metal or DES
• Clinically significant rate of restenosis
  observed in patients receivung DES.

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Reasons given for discrepancy between 2007 and
2009

• Use of primary PCI more prevalent
• Pre treatment with clopidogrel and longer
  duration of antiplatelet therapy.
• Previous study included patients with more than 1
  stent.

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Thank YOU..