Repairing Coronary Arteries, pumpsandpipesmdhc

Repairing Coronary Arteries Neal Kleiman Director Cardiac Catheterization Laboratory Methodist DeBakey Heart Center Professor of Medicine Weill Medical College of Cornell University

Courtesy of Dr. Paul Tierstein

Angioplasty: The Thirtieth Anniversary Gruntzig Patient

Balloon Angioplasty: The Initial Concept “ Footprints in the snow”

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

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?

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

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? DCA picture

Why not grind it up?

Why not vaporize it?

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

Stents 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 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 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) Elastomeric, Polyolefin Derivate

Sirolimus Drug Eluting Stent System (Cypher) PBMA / EVA

Heterogeneity of Re-Endothelializaiton in a Drug-Eluting Stent Finn, Circulation: 2007

Cumulative Incidence of DES Thrombosis in the Rotterdam-Bern Registry 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

0.6%/year late thrombosis

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

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

Evolution of PCI: The Dominant Coronary Revascularization Therapy Dr. Don Baim, FDA Panel Meeting December 2006 Progressive improvements in success, safety, and durability, as serial new technologies have been launched. Innovations over time 0 10 20 30 40 POBA early POBA late Stent early Stent late DES Event Rate % 1977 1985 1997 1994 2003-present Failure Em CABG Restenosis Stent thrombosis VLST