Repairing Coronary ArteriesRepairing Coronary Arteries

Neal KleimanDirector Cardiac Catheterization Laboratory

Methodist DeBakey Heart CenterProfessor of Medicine

Weill Medical College of Cornell University

Neal KleimanDirector Cardiac Catheterization Laboratory

Methodist DeBakey Heart CenterProfessor of Medicine

Weill Medical College of Cornell University

Courtesy of Dr. Paul Tierstein

Courtesy of Dr. Paul Tierstein

Angioplasty: The Thirtieth

Anniversary

Angioplasty: The Thirtieth

Anniversary

Gruntzig

Patient

Balloon Angioplasty: The Initial Concept

Balloon Angioplasty: The Initial Concept

“Footprints in the snow”

Mechanism of AngioplastyMechanism of Angioplasty

Landau C et al. N Engl J Med 1994;330:981-993

Angioplasty: Issues Seeking Solutions

Angioplasty: Issues Seeking Solutions

The atheromatous plaque is part of the arterial wall, not simply a harmful deposit on a normal structure

Blood vessels rarely follow linear courses The artery is reactive and blood is reactive!

– All intra-arterial procedures injure the wall and provoke scar formation (“restenosis”)

– Blood is a substance that when provoked, turns from a viscous fluid into a solid (clot)

How are these problems manifest following angioplasty?

How are these problems manifest following angioplasty?

Failed procedure: 5% (vessel just can’t be dilated)

Abrupt closure: 5% Periprocedural heart attack: 10% (3/4 of

these are very small) Renarrowing or restenosis: 30% - 40%,

particularly in long areas of blockage, and patients with diabetes.

Angioplasty – The major issue for the last thirty years

Angioplasty – The major issue for the last thirty years

How to modulate the vascular and blood reactivity to the barotrauma caused by balloon injury.– Preventing vascular smooth muscle cells from

forming “scars” inside blood vessels– Preventing platelets from forming clots on the

injured areas

Chung, I.-M. o et al. J Am Coll Cardiol 2002;40:2072-2081

Restenosis Or “Scar Formation” After Angioplasty – The Role Of Tissue Ingrowth

Why not Scoop out the plaque?Why not Scoop out the plaque?

DCA picture

Why not grind it up?Why not grind it up?

Why not vaporize it?Why not vaporize it?

316 L Stainless Steel 130-140 strut) or Co-Cr Alloy (80-90 strut)

Stents vs POBAStents vs POBA

Improved arterial lumen– Reduces recoil– Scaffolds tears and dissections

Reduces abrupt vessel closure Restenosis reduced from 40% 20% No documented reduction the rates of

death or heart attack

Drug Eluting StentsDrug Eluting Stents

Stent + Drug + Polymer The drug prevents cell replication by

interfering with cellular reproduction. Reduces in-stent renarrowing 20% <5%

and the need for repeat procedures In 2006, accounted for 90% of stent use in

the US and 30%-50% in Europe In 2007, use is approx 70% in US and

20% in Europe

Drug Eluting StentsDrug Eluting Stents

Polymer controls the release of drug at the appropriate rate (currently 2-4 weeks)

Strut separation and contact with the arterial wall influence the rate of drug delivery and possibly the clinical outcome.

The stent thus becomes both a scaffold and a platform

Paclitaxel Drug Eluting Stent System (Taxus)Paclitaxel Drug Eluting Stent System (Taxus)

Elastomeric, Polyolefin Derivate

Sirolimus Drug Eluting Stent System (Cypher)Sirolimus Drug Eluting Stent System (Cypher)

PBMA / EVA

Heterogeneity of Re-Endothelializaiton in a Drug-Eluting

Stent

Heterogeneity of Re-Endothelializaiton in a Drug-Eluting

Stent

Finn, Circulation: 2007

Cumulative Incidence of DES Thrombosis in the Rotterdam-Bern Registry

Cumulative Incidence of DES Thrombosis in the Rotterdam-Bern Registry

0.6%/year late thrombosis

Daemen: Lancet: 2007:369: 667

Accumulated early and midterm implantation experience

8,146 Patients initially 981 at f/u

24% of patients with thrombosis were on clopidogrel and aspirin

16 RCTs; 8,695 Patients

Follow-up to 4 Years

Reduced Risks of Re-intervention: HR = 0.74 (0.63-0.87) and

Stent Thrombosis: HR = 0.66 (.46-.94)

No in Risk of MI: HR = 0.84 (0.69-1.03)

16 RCTs; 8,695 Patients

Follow-up to 4 Years

Reduced Risks of Re-intervention: HR = 0.74 (0.63-0.87) and

Stent Thrombosis: HR = 0.66 (.46-.94)

No in Risk of MI: HR = 0.84 (0.69-1.03)

New Approaches to Stenting Coronary Arteries

New Approaches to Stenting Coronary Arteries

Thinner stent struts New polymers

– Phosphorylcholine (PC) – mimics the outer layer of a normal cell membrane

– Bioabsorbable polymers – elute the appropriate medication and then disappear

Bioabsorbable stents– Entire stent itself is reabsorbed over a period of six

months

Endothlial Precursor Cell (EPC) Capture

Innovations over time

0

10

20

30

40

POBA early POBA late Stent early Stent late DES

Even

t Rat

e %

1977 1985 19971994 2003-present

Evolution of PCI: The Dominant Coronary Revascularization Therapy

Evolution of PCI: The Dominant Coronary Revascularization Therapy

FailureEm CABGRestenosisStent thrombosisVLST

Dr. Don Baim, FDA Panel Meeting December 2006

Progressive improvements in success, safety, and durability, as serial new technologies have been launched.