FREEDOM Trial

Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease

Regional Update as of October 9, 2008

1417 patients
US - 296 Canada 295 Europe- 348 Poland 79 Spain 75 Germany 69 France - 49 Italy - 29 UK 11 Israel 11 Switzerland 6 Czech Republic 19 Brazil 234 Argentina 55 Mexico - 38 Colombia -17 Australia 59 New Zealand 26 India - 49

136 sites

US 46 sites Canada 18 sites Mexico 1 site South America - 12 sites Argentina 5 sites Brazil 4 sites Colombia 2 sites Europe 36 sites Italy 3 sites France 5 sites Spain 6 sites Switzerland 1 site Germany 7 sites Poland 6 sites UK 3 sites Israel 3 sites Czech Republic -2 sites Australia 15 sites New Zealand 3 sites India 6 sites

FREEDOM Recruitment
1417 1408
1298

2005

2006

2007

2008

Top 5 Recruiting Sites Worldwide

US
Mount Sinai Medical Center

CANADA
Vancouver Hospital and Health Sciences Center Montreal Heart Institute

SOUTH AMERICA
InCor Heart Institute Institute Dante Pazzanese of Cardiology

SUCCESSES

FREEDOM is now the largest database of diabetic subjects with multivessel coronary disease

SUCCESSES
Multidisciplinary approach to risk factor modification with oversight from the Diabetes and medical management committee has been effective
Variable (Means) Baselin 1 yr f/u e 79.3 42.2 165.6

LDL 89.5 mg/dl HDL 40.1 mg/dl TG mg/dl 192.8

SUCCESSES
Newsletters, bulletins and patient diaries well received United States/ Canada trial coordinators meeting held Provision of stents, clopidogrel and abciximab well worked out worldwide Small group conference calls with Dr. Fuster and Investigators arranged on a weekly basis to identify obstacles to recruitment or

ROOM FOR IMPROVEMENT

Variable (Means) HbA1C SBP mm/Hg DBP mm/Hg Smoking % Baseline 7.6 133.9 76.0 1 yr f/u 7.6 134 75.7

Current smoker
Waist cm

15.0%
103.6

7.6%
104.2

Baseline Demographics
Treatment Arm A B (N=593) (N=592) Age (mean) Female 63.4 28.9% 63.0 29.5%

Diabetes Mellitus: Type I

Hypertension Hyperlipidemia

4.8%
83.9% 85.1%

4.8%
84.7% 81.9%

Diabetes Complications
Treatment Arm A (N=593) Complications associated with diabetes Diabetic nephropathy Diabetic neuropathy 18.0% 4.9% 11.2% B (N=592) 18.9% 8.6% 8.8%

Diabetic foot ulcer

Diabetic retinopathy

2.8%
6.3%

0.7%
7.6%

Extremity amputation
Duration of diabetes (years) PVD above diaphragm PVD below diaphragm

1.2%
10.1 1.9% 10.0%

0.2%
10.3 3.4% 8.3%

Baseline Results
Mean Treatment Arm

A (N=593)
HbAlc % 7.9

B (N=592)
7.6

LDL mg/dL
HDL mg/dL Triglycerides mg/dL Creatinine mg/dL SPB mm/Hg

91.4
39.4 196.9 1.1 135

92.0
40.0 173.3 1.1 133

DBP mm/Hg Waist circumference

77 103.5

76 103.3

Baseline Diabetes Meds

Treatment Arm
A (N=593) Insulin Sulfonylurea Glyburide Glipizide Glimepiride Sulfonylurea other 35.3% 40.8% 17.9% 5.4% 5.4% 12.2% B (N=592) 28.9% 47.9% 22.1% 6.6% 5.8% 14.0%

Biguanides Alpha-Glucosidase inhibitor

Thiazolidinedione Rosiglitazone Pioglitazone Repaglinide Nateglinide

52.5% 2.0%
9.7% 64.9% 35.1% 1.0% 0.3%

52.3% 1.5%
10.1% 59.3% 40.7% 1.2% 0.0%

History of Present Illness

A (N=593) Stable Coronary Heart Disease 68.3% B (N=592) 71.4%

Acute Coronary Syndrome (ACS) ST elevation MI(>72 hrs prior to admission Non-ST elevation ACS

31.7% 17.1% 82.9%

28.6% 17.3% 82.7%

NYHA CHF Classification (Class III/IV excluded) Class I

74.5%

72.6%

Baseline Meds
Treatment Arm A (N=593) Lipid Lowering agents Statins 85.9% 95.9% B (N=592) 86.0% 96.8%

Fibrates
Ezetemibe Niacin Omega-3 fatty acids Others

5.7%
5.5% 0.8% 0.4% 2.2%

5.0%
5.8% 1.6% 1.0% 0.4%

Baseline Cardiac Meds

Treatment Arm A (N=593) B (N=592)

ACE Inhibitor ARB Aldosterone Antagonist Loop Diuretic Thiazide diuretic Beta Blocker Calcium Channel Blocker Nitrates

76.8% 17.8% 4.2% 14.6% 16.4% 84.4% 35.0% 46.7%

79.3% 19.0% 4.0% 11.8% 16.5% 84.2% 38.7% 44.3%

PCI Procedure Summary

PCI/DES
Staging: % unstaged procedure % staged procedure % staged procedures involving >1 hospitalization 65.9% 34.1% 67.7%

Mean total # of lesions attempted across all stages

Mean total # drug-eluting stents placed per patient (across all stages) Reopro used during index procedure (stage 1 for staged procedures) Heparin administered Bivalirudin administered

3.6 1.4
4.2 1.9 54.9% 83.1% 16.3%

Lesion Characteristics in PCI/DES Arm

Lesions Reference vessel diameter (mm): <2.5 2.5-3.0 3.0-3.5 3.5-4.0 >4.0 Chronic total occlusion Bifurcation lesion Balloon angioplasty alone Direct stenting 16.1% 47.7% 26.8% 8.4% 0.9% 4.6% 11.3% 3.6% 27.0%

Planned Treatment Strategy for CABG at Time of Qualifying Angiogram

Planned Strategy Vessels intended to graft:
LAD D1 D2 D3 RCA RAMUS CIRCUMFLEX OM1 OM2 OM3 LPDA RPDA RPLV AM 95.4% 29.8% 5.8% 0.3% 47.5% 7.0% 24.6% 42.9% 22.5% 5.3% 3.5% 28.3% 5.0% 0.8%

Qualifying Angiogram
(N=1165)

Complete revascularization anticipated

86.3%

CABG Procedure Summary

CABG Off pump LIMA to LAD 22.1% 88.2%