CORE Conference, October 26, 2009

Brief assessment of the physiology of CAD

Management options
Stent Controversy Drugs or Bare

What does it mean to the clinician

Future ?

 Atherosclerotic process

Thrombosis and platelets

Atherothrombosis: A Generalized and Progressive Process

Thrombosis
Unstable angina ACS MI Ischemic stroke/TIA

Atherosclerosis

Critical leg ischemia

Intermitent claudication CV death

Stable angina/ Intermittent claudication

Adapted from Libby P. Circulation. 2001;104:365-372.

C C
Soft Lipid Core

D
Ulceration

C
B A B D

Courtesy of Steven E. Nissen, MD, Cleveland Clinic.

Mechanisms of Platelet Activation and Inhibition

Kereiakes, D. J. et al. J Am Coll Cardiol Intv 2008;1:111-121

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

Vulnerable Plaque
Vulnerable Blood

Vulnerable Myocardium

Vulnerable Patient
Naghavi, Circulation. 2003;108:1664-72

Culprit lesion stented

Evidence of multiple plaques

Endothelial area stented = 0.0002 m2

Total endothelial area = 1000 m2

1/5,000,000

 Management options
Medical
CABG PTCA Stents BMS DES

Imputed Effect of Drug-Eluting Stents in the COURAGE Trial

Diamond, G. A. et al. J Am Coll Cardiol 2007;50:1604-1609

Copyright 2007 American College of Cardiology Foundation. Restrictions may apply.

Odds Ratios for Nonfatal Myocardial Infarction in Individual Trials Comparing the PCIBased Strategy With Medical Treatment Strategy

Schomig, A. et al. J Am Coll Cardiol 2008;52:894-904

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

Odds Ratios for Cardiac Death in Individual Trials Comparing the PCI-Based Strategy With Medical Treatment Strategy

Schomig, A. et al. J Am Coll Cardiol 2008;52:894-904

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

Odds Ratios for Mortality in Individual Trials Comparing the PCI-Based Strategy With Medical Treatment Strategy

Schomig, A. et al. J Am Coll Cardiol 2008;52:894-904

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

 PTCA

BMS
DES

60 50 40 30 20 10 0 POBA BMS
1982 -1993 1992 -2003

High Median Low SAT

Histologic Sections of the Iliac Arteries 42 Days After Stent Implantation and Bar Graph of Percent Stenosis

Ribichini, F. et al. J Am Coll Cardiol 2007;50:176-185

Copyright 2007 American College of Cardiology Foundation. Restrictions may apply.

 General review of trails thrombosis, death

The diabetic - comment

Acute ischemic syndromes a spectrum issue On vs Off label ideal vs real world

Pooled Analysis of RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS Trials

Kaul, S. et al. J Am Coll Cardiol 2007;50:128-137

Copyright 2007 American College of Cardiology Foundation. Restrictions may apply.

RRs for Stent Thrombosis in 17 Randomized Trials Comparing SES With BMS

Kastrati, A. et al. J Am Coll Cardiol 2007;50:146-148

Copyright 2007 American College of Cardiology Foundation. Restrictions may apply.

RRs for Death in 17 Randomized Trials Comparing SES With BMS

Kastrati, A. et al. J Am Coll Cardiol 2007;50:146-148

Copyright 2007 American College of Cardiology Foundation. Restrictions may apply.

Indications for DES use "On-label" or FDA-approved use

CYPHER Sirolimus-eluting Coronary Stent (5) For improving coronary luminal diameter in patients with symptomatic ischemic disease due to discrete de novo lesions in native coronary arteries 30 mm in length 2.53.5 mm in diameter 50%99% stenosis TAXUS Express 2 Paclitaxel-Eluting Coronary Stent System (6) For improving luminal diameter for the treatment of de novo lesions in native coronary arteries 28 mm in length 2.53.75 mm in diameter 50%99% stenosis

Indications for DES use "Off-label" or beyond FDA-approved use

Lesion subsets Multivessel disease Left main disease Bifurcation lesions Chronic total occlusions (CTO) In-stent restenosis (ISR) Small vessels (<2.5 mm in diameter) or large vessels (>3.75 mm in diameter) Long lesions requiring multiple or overlapping stents Saphenous vein grafts (SVG) Thrombus containing lesions (acute MI) High-risk patient subsets Diabetics Renal dysfunction

Repeat Revascularization Event Rates

Mulukutla, S. R. et al. J Am Coll Cardiol Intv 2008;1:139-147

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

Death or Myocardial Infarction Event Rates

Mulukutla, S. R. et al. J Am Coll Cardiol Intv 2008;1:139-147

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

Relative Benefit of DES Over BMS for Safety and Efficacy

Mulukutla, S. R. et al. J Am Coll Cardiol Intv 2008;1:139-147

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

Short-Term Outcomes for STEMI Patients Undergoing Stent Placement in New York from October 2003 to December 2004

Outcome
Observed in-hospital mortality rate (%) Risk-adjusted inhospital mortality rate (%) Observed same-stay CABG rate (%) Risk-adjusted samestay CABG rate (%)

BMS (n = 772) 2.46 2.39

DES (n = 1,154) 1.39 1.42

p Value
0.12 0.14

1.04

0.52

0.27

1.02

0.53

0.35

Adjusted Rates of Subsequent PCI in Target Vessel

Hannan, E. L. et al. J Am Coll Cardiol Intv 2008;1:129-135

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

Adjusted Rates of Subsequent CABG

Hannan, E. L. et al. J Am Coll Cardiol Intv 2008;1:129-135

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

Risk-Adjusted Mortality

Hannan, E. L. et al. J Am Coll Cardiol Intv 2008;1:129-135

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

Hazard Ratios (BMS/DES) for STEMI Patients Undergoing Stent Placement in New York

Outcome Mortality CABG revascularization Target vessel revascularization

Unadjusted HR for Adjusted* HR for Primary Primary Angioplasty Angioplasty Cases Cases BMS/DES (95% CI) BMS/DES (95% CI) 1.53 (1.022.29) 1.74 (1.122.71) 1.25 (0.841.88) 2.01 (1.213.34) 2.33 (1.314.16) 1.15 (0.741.78)

Adjusted for individual hospital, IV GPIIb/IIIa platelet inhibitors given prior to the operation, number of vessels diseased, region of disease (LAD involvement or proximal LAD involvement), age, female gender, ejection fraction, peripheral vascular disease, cerebrovascular disease, hemodynamic instability, shock, diabetes, and renal failure. HR = hazard ratio.

 Definition

Perspective

Stent Thrombosis Definitions and Classification

"Academic Research Consortium" definitions (4) Definite ST Probable ST Acute coronary syndrome with angiographic or autopsy evidence of thrombus or occlusion 1 Unexplained deaths within 30 days following PCI 2 Acute myocardial infarction involving the targetvessel territory without angiographic confirmation

Possible stent thrombosis Temporal classification Acute ST Subacute ST Late ST Very late ST

All unexplained deaths occurring at least 30 days following PCI During PCI or within the following 24 h Between 1 and 30 days following PCI Between 1 month and 1 yr following PCI More than 1 yr following PCI

PCI = percutaneous coronary intervention; ST = stent thrombosis.

Suggested Risk Factors For Late and Very Late Stent Thrombosis
Patient characteristics Diabetes, acute coronary syndrome, renal failure, advanced age, reduced ejection fraction, major adverse cardiac event within 30 days of the original procedure, previous myocardial infarct

Coronary anatomy

Type C lesion, bifurcation, in-stent restenosis, multivessel disease, calcification, total occlusion, stent length, bypass graft
Reduced coronary flow after stenting, stent underexpansion, residual dissection, "crush" technique, side branch occlusion, need for glycoprotein IIb/IIIa inhibitor

Procedural characteristics

Discontinuation of dual antiplatelet therapy Clopidogrel resistance Hypersensitivity reaction Delayed arterial healing

 How long to treat with clopidogrel

What else and how much

When can I have surgery How should the stent be treated in prep for surgery

Oops !

Cumulative Incidence of Definite ST in 8,146 Patients During a 4-Year Follow-Up Period

Wenaweser, P. et al. J Am Coll Cardiol 2008;52:1134-1140

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

Cumulative Incidence of Ischemic Adverse Events in 8,146 Patients During 4 Years of Follow-Up

Wenaweser, P. et al. J Am Coll Cardiol 2008;52:1134-1140

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

Table 1 Clinical and Procedural Characteristics of Patients With and Without Definite ST Overall Population ST No ST
(n = 8,146) Age (yrs), mean SD Male gender, % Hypertension, % Current smoking, % Family history of CAD, % Dyslipidemia, % Diabetes, % LVEF (%), mean SD Renal impairment, % ACS at presentation, % Bifurcation treatment, % Sirolimus-eluting stent, % Total stent length/patient (mm), mean SD Number of stents/patient, mean SD Average stent diameter/patient (mm), mean SD 62.8 11.5 74.5 46.5 36.8 28.1 50.9 16.3 55 12 4.1 55.2 11.8 47.9 36.3 25.9 1.96 1.23 2.94 0.38 (n = 192) 59.4 12.1 75.0 42.2 41.7 29.2 50.0 20.8 52 12 2.6 67.7 17.9 43.2 (n = 7,954) 62.9 11.5 74.5 46.6 36.7 28.1 50.9 16.2 55 12 4.2 54.9 11.6 48.0 p Value <0.001 0.88 0.23 0.16 0.75 0.81 0.09 0.035 0.48 <0.001 0.06 0.19 <0.001 <0.001 0.048

44.0 38.8 36.1 25.5 2.33 1.71 1.95 1.21 2.88 0.32 2.94 0.38

Interindividual Variability in Platelet Aggregation

Angiolillo, D. J. et al. J Am Coll Cardiol 2007;49:1505-1516

Copyright 2007 American College of Cardiology Foundation. Restrictions may apply.

Guideline Recommendations 12 months dual antiplatelet therapy post DES 1 month dual antiplatelet therapy post BMS

This is a guideline which is neither absolute nor binding. It is best to place these recommendations in light of the clinical circumstances and the particulars of the history. Given the current rate of change of the clinical data and assumptions made to date they probably reflect a minimum standard of care.

ACC / AHA recommendations due to the extended risk of SAT advise continuation of the Plavix for a minimum of 1 year in patients managed with DES

Many interventionalists are advocating continuation for up to 2 years depending on the complexity of the anatomy

Perioperative Stent Thrombosis Prevention Strategies

Brilakis, E. S. et al. J Am Coll Cardiol 2007;49:2145-2150

What about emergencies

You can wait 5 days for the plavix effect to dissipate

Then you can contact your attorney..

You really can t wait 5 days for the plavix effect to dissipate

You can be aware of the effects of the drug and treat accordingly intraoperatively and post operatively.

Schematic of a Kinetic Model of Restenosis, Thrombosis, and Adverse Events Post-Stenting

Kaul, S. et al. J Am Coll Cardiol 2007;50:128-137

Copyright 2007 American College of Cardiology Foundation. Restrictions may apply.

Remember, the next time you wish to comment upon the size of boots a cardiologists mother wears As we ply our trade and experience success,
You then have opportunity to experience yours