1. Clinical need for determination of vulnerable plaques
Robert L Wilensky, MD
Professor of Medicine
Hospital of the University of Pennsylvania

2. Robert L. Wilensky, MD DISCLOSURES Grants/Contracted Research
GlaxoSmithKline
Ownership Interest (Stocks, Stock Options or Other Ownership Interest)
Johnson & Johnson
I intend to reference unlabeled/ unapproved uses of drugs or devices in my presentation.
I intend to reference a darapladib which is in Phase III clinical trial evaluation.

3. Acute coronary syndromes: US prevalence and incidence 2006
7.9 million with history of Myocardial Infarction
Incidence
1.37 million hospital discharges for ACS
810,000 for Myocardial Infarction
537,000 for Unstable Angina
18,000 Myocardial Infarction and Unstable Angina
610,000 new MIs and 325,000 recurrent MIs
29%–32% STEMI
Lloyd-Jones D, et al. Circulation. 2009;119(3):e21-181

4. Mortality rate after a first MI
1-year (%)
5-year (%)
40–69 years of age
White men 8 15
White women 12 22
Black men 14 27
Black women 11 32
≥70 years of age 50 56 26 28 62
Lloyd-Jones D, et al. Circulation. 2009;119(3):e21-181

5. Rate of recurrent MI or fatal CHD
5-year (%)
40–69 years of age
White men 14
White women 18
Black men 27
Black women 29
≥70 years of age 24 30 32
Lloyd-Jones D, et al. Circulation. 2009;119(3):e21-181

6. Mortality: Fast Stats
1990–1999 in-hospital acute MI mortality declined from 11.2% to 9.4%
Annual mortality rate 16% for MI
Sudden death rate 4–6 times higher in persons with history of MI than general population
Ischemic heart disease is a leading cause of chronic congestive heart failure
Lloyd-Jones D, et al. Circulation. 2009;119(3):e21-181

7. Leading Causes of Death in the United States – 2005
(accessed May 19, 2009)
Lloyd-Jones D, et al. Circulation. 2009;119(3):e21-181

8. Younger age in women is associated with increased risk of adverse outcome in acute coronary syndromes
One-year death, MI and revascularization rates
Circulation 2004;110:III-1936.

9. Clinical studies summary: Angiography in infarct-related artery
Content Points:
In a review of coronary plaque disruption, Falk et al31 collated data from studies by Ambrose et al,33 Little et al,34 Nobuyoshi et al,35 and Giroud et al.36
The slide summarizes the number of patients with MI caused by rupture of plaques causing either > 70%, 50%-70%, or < 50% stenosis. In 68% of cases, the coronary event was caused by plaques causing < 50% stenosis.

10. Unstable angina resulting in sudden death

11. Unstable angina is associated with widespread neutrophil activation.
N Engl J Med 2002;347:5

12. VBWG

13. VBWG

14. PROVE-IT: Estimates of the HR for 2° secondary end points and the individual components of the 1° end point
Figure 4. Estimates of the Hazard Ratio for the Secondary End Points and the Individual Components of the Primary End Point in the High-Dose Atorvastatin Group, as Compared with the Standard-Dose Pravastatin Group. CI denotes confidence interval, CHD coronary heart disease, and MI myocardial infarction. Revascularization was performed at least 30 days after randomization.
Cannon C et al. N Engl J Med 2004;350:1495

15. REACH: 1-yr CV event rates as a function of number of symptomatic disease locations
Steg, P.G. et al. JAMA 2007;297:1197

16. COURAGE trial PCI+OMT OMT Death 7.6% 8.3% MI 13.2% 12.3%
ACS % %
Total: % %
4.6 year follow-up
Figure 2. Kaplan-Meier Survival Curves. In Panel A, the estimated 4.6-year rate of the composite primary outcome of death from any cause and nonfatal myocardial infarction was 19.0% in the PCI group and 18.5% in the medical-therapy group. In Panel B, the estimated 4.6-year rate of death from any cause was 7.6% in the PCI group and 8.3% in the medical-therapy group. In Panel C, the estimated 4.6-year rate of hospitalization for acute coronary syndrome (ACS) was 12.4% in the PCI group and 11.8% in the medical-therapy group. In Panel D, the estimated 4.6-year rate of acute myocardial infarction was 13.2% in the PCI group and 12.3% in the medical-therapy group.
Boden W et al. N Engl J Med 2007;356:1503

17. Braunwald, E. J Am Coll Cardiol 2006;47:C101
Proposed algorithm for the detection of plaques likely to result in acute coronary syndromes or death
Braunwald, E. J Am Coll Cardiol 2006;47:C101

18. Potential for new medications to reduce atherosclerosis risk
Numerous large pharmaceutical companies are no longer pursuing agents to reduce atherosclerosis risk.
clinical trials.gov- Atherosclerosis studies:
739
Number of novel medications being studied: 12
Number of on-going studies 14

19. Summary
A significant number of patients with coronary artery disease will suffer recurrent events despite optimal medical therapy.
No current diagnostic approach can locate the lesion with increased likelihood of rupture.
Evaluation of high-risk lesions in high risk patients will require a combination of non-invasive and focused invasive imaging.