1. Regional and Practice Variation in Adherence to Guideline Recommendations for Secondary and Primary Prevention Among Outpatients with Atherothrombosis or Risk Factors in the US: A Report From the REACH Registry Amit Kumar, Gregg C. Fonarow, Kim A. Eagle, Alan T. Hirsch, Robert M. Califf, Mark J. Alberts, William E. Boden, P. Gabriel Steg, Mingyuan Shao, Deepak L. Bhatt, Christopher P. Cannon, on behalf of the REACH Registry Investigators

2. Global REACH Registry: Study Design

3. Primary Objective: To explore the impact of both classic and new risk factors on the prevalence of cardiovascular (CV) ischemic events among patients with, or at high risk for, atherothrombotic disease, on an international basis Global REACH Registry Objectives Additional Aims: Assess use of risk management strategies and 1-, 2-, 3- and 4-year outcomes in a broad outpatient population encompassing various geographic regions and physician specialties 1. Ohman EM et al, on behalf of the REACH Registry Investigators. Am Heart J 2006;151(4):786.e1-10.

4. Must include: Signed written informed consent Patients aged ≥45 years At least of four criteria 1 1.Documented cerebrovascular disease Ischemic stroke or TIA (CVD) 2.Documented coronary disease Angina, MI, angioplasty/ stent/bypass (CAD) 3.Documented historical or current intermittent claudication associated with ABI <0.9 (PAD) At least atherothrombotic risk factors 3 1.Male aged  65 years or female aged  70 years 2.Current smoking >15 cigarettes/day 3.Type 1 or 2 diabetes 4.Hypercholesterolemia 5.Diabetic nephropathy 6.Hypertension 7.ABI <0.9 in either leg at rest 8.Asymptomatic carotid stenosis  70% 9.Presence of at least one carotid plaque Global REACH Registry Inclusion Criteria 1. Ohman EM et al, on behalf of the REACH Registry Investigators. Am Heart J 2006;151(4):786.e1-10. ABI, ankle-brachial index; MI, myocardial infarction; TIA, transient ischemic attack.

5. Global REACH Registry Exclusion Criteria Anticipated difficulty in patient returning for follow-up visit Patient is currently hospitalized Patient is currently participating in a clinical trial 1. Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.

6. *Timelines are for worldwide participation; local timelines will be shorter Global REACH Registry Timeline BaselineFollow-up at 12  3 months Follow-up at 24  3 months Follow-up at 33  3 months Follow-up at 45  3 months Timing*Dec 2003 to June 2004 From baseline time Last follow-up March 2006 June 2006 to June 2007 June 2007 to June 2008 Required Data Subject Data Form: Section 1 Subject Data Form: Section 2 (progression since baseline) Subject Data Form: Section 3 (progression since last follow-up) Subject Data Form: Section 4 (progression since last follow-up) Subject Data Form: Section 5 (progression since last follow-up) Patient details, history and clinical examination Regular medications Employment status Clinical outcomes Vascular interventions Regular medications Employment status

7. Participating physicians Pre-defined at start of Registry Based on local practice population General practitioners, specialists Mainly office-based, some hospital representation Representative of: Local environment Country geography Global Physician Selection How were they selected? What is their profile? 1. Ohman EM et al, on behalf of the REACH Registry Investigators. Am Heart J 2006;151(4):786.e1-10.

8. Main Specialty Breakdown of US Practitioner Involvement (n=1,599) GP or Internist Cardiologist Endocrinologist, Neurologist, Vascular Surgeon, Angiologist, Other 1.Eagle KA et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(2):91-97. 86.8% 9.7% 3.5%

9. Patients Recruitment at each site Maximum 20 per site Within overall Registry timelines Patient inclusion criteria Documented atherothrombotic disease, or with ≥3 atherothrombotic risk factors Real-life setting Global Patient Selection: Patients Fitting Inclusion Criteria How were they selected? What is their profile? 1. Ohman EM et al, on behalf of the REACH Registry Investigators. Am Heart J 2006;151(4):786.e1-10.

10. REACH Registry: Adherence to Primary and Secondary Prevention Guidelines in the US

11. Background and Objectives Proven risk-reducing therapies for patients with or at risk for atherothrombotic events include antihypertensive, antiplatelet, antidiabetic, and lipid- lowering agents Hospital-based studies have shown that better adherence to guideline-recommended risk-reducing therapies improves clinical outcomes This analysis of the US cohort of the REACH Registry was undertaken to analyze the use of risk-reducing therapies for both primary and secondary atherothrombosis prevention, stratified by US Census Region and physician specialty 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3).

12. Patient Characteristics at Baseline – Stratified by US Census Region 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3). Total (N = 25,686) Northeast (n = 4775) Midwest (n = 6267) South (n = 9865) West (n = 4507) Symptomatic, %74.272.576.474.572.5 Asymptomatic, %25.827.523.625.527.5 Men, %57.057.956.055.760.3 ≥65 years of age, %69.171.469.566.072.4 Caucasian, %80.283.887.276.674.4 African American, %10.89.89.614.84.8 Hispanic, %5.53.31.66.211.7 Asian, %2.82.61.31.78.0 Diabetes, %51.749.650.852.553.2 Hypertension, %87.587.687.988.085.9 Hypercholesterolemia, %82.685.182.681.482.6 Obesity, %42.143.445.342.136.9 Overweight, %35.834.435.536.036.7 Former smoker, %43.141.543.442.545.3 Current smoker, %14.413.514.515.811.8

13. US Patient Characteristics at Baseline – Stratified by Physician Specialty 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3). General Practitioner (N = 11,662) Internist (n = 11,711) Cardiologist (n = 2401) Endocrin- ologist (n = 840) Other (n = 1249) Symptomatic,%71.673.693.963.076.1 Asymptomatic, %28.426.46.137.023.9 Men, %55.456.866.760.153.4 ≥65 years old, %66.472.867.864.670.4 Caucasian, %80.178.884.184.073.5 African American, %10.311.87.35.913.8 Hispanic, %6.25.24.94.78.7 Asian, %2.73.62.84.43.0 Diabetes, %52.252.036.189.253.2 Hypertension, %88.188.681.787.889.2 Hypercholesterolemia, %81.483.487.088.177.4 Obesity, % (BMI ≥30 kg/m 2 ) 44.440.734.550.739.9 Overweight, % (BMI 25 to <30 kg/m 2 ) 34.636.640.932.134.5 Former smoker, %41.343.651.742.539.1 Current smoker, %16.812.810.411.413.3

14. Use of Risk-Reducing Medications at Baseline in US Patients – Total Population 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3).

15. Antidiabetes Medication Use at Baseline Among US Patients with Diabetes or Elevated Glucose – Stratified by Physician Specialty 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3). General Pract. (n = 6051) Internist (n = 6058) Cardiol- ogist (n = 862) Endocrin- ologist (n = 748) Other (n = 646) Total ≥1 Antidiabetic, %91.990.690.397.191.491.6 Insulin,%26.027.729.153.436.428.6 Biguanide, %45.541.235.542.032.742.6 Sulfonylurea, %47.445.042.039.639.545.4 Thiazolidinedione, %33.631.127.532.628.332.1 Other Antidiabetic, %8.18.89.77.910.88.3

16. Antihypertensive Medication Use at Baseline Among US Patients with Diagnosed Hypertension or Elevated BP at Enrollment – Stratified by Physician Specialty 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3). General Pract. (n = 10,255) Internist (n = 10,350) Cardiol- ogist (n = 1955) Endocrin- ologist (n = 732) Other (n = 1106) Total ≥1 Antihypertensive, %99.1 98.9 99.099.1 ACE Inhibitor,%51.347.850.951.643.649.6 ARB, %27.030.725.232.728.128.3 β-Blocker, %50.352.370.546.249.652.6 Ca 2+ Channel Blocker, %35.537.932.027.638.836.0 Diuretic, %52.753.448.950.852.352.9 Other Antihypertensive, %12.413.614.315.619.013.2

17. Use of Risk-Reducing Medications in the US – Overall Population Antiplatelet Agent StatinACE-I/ARBβ-Blocker ≥ 3 of 4 (2° Prev) Patients (%) 76.5 76.7 81.7 76.577.1 67.9 65.3 50.4 57.4 65.6 75.3 79.1 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3). ≥ 2 of 3 (1° Prev) Total (N = 25,686) Secondary Prevention (n = 19,069) Primary Prevention (n = 6617) 61.6

18. Use of Risk-Reducing Medications in the Secondary Prevention Population – Stratified by US Census Region Antiplatelet Agent StatinACE-I/ARBβ-Blocker ≥ 3 of 4 (2° Prev) Patients (%) 82.3 81.1 83.0 80.6 75.0 77.4 64.7 66.4 52.9 64.7 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3). 81.0 63.4 55.2 75.2 64.7 58.9 65.6 70.7 63.7 66.4 Northeast (n = 3462) Midwest (n = 4786) South (n = 7353) West (n = 3267)

19. Use of Risk-Reducing Medications in the Primary Prevention Population – Stratified by US Census Region Antiplatelet Agent StatinACE-I/ARB ≥ 2 of 3 (1° Prev) Patients (%) 62.4 59.1 62.1 79.7 74.9 77.5 76.0 75.0 77.3 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3). 62.2 78.978.2 74.7 79.7 80.5 75.4 Northeast (n = 1313) Midwest (n = 1481) South (n = 2512) West (n = 1240)

20. Use of Risk-Reducing Medications in the Secondary Prevention Population – Stratified by Physician Specialty Antiplatelet Agent StatinACE-I/ARB ≥ 3 of 4 (2° Prev) Patients (%) 81.8 79.1 84.2 82.6 70.0 66.0 52.5 51.6 56.0 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3). 78.8 70.2 73.9 68.3 74.2 66.2 56.7 β-Blocker General Practitioner (n = 8352) Internist (n = 8615) Cardiologist (n = 2254) Endocrinologist (n = 529) Other (n = 951) 83.7 57.5 66.7 77.1 81.0 74.3 64.3 55.2 62.9

21. Use of Risk-Reducing Medications in the Primary Prevention Population – Stratified by Physician Specialty Antiplatelet Agent StatinACE-I/ARB ≥ 2 of 3 (1° Prev) Patients (%) 61.9 60.2 61.2 79.6 75.5 71.3 78.979.5 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3). 57.1 76.8 74.5 83.0 General Practitioner (n = 3310) Internist (n = 3096) Cardiologist (n = 147) Endocrinologist (n = 311) Other (n = 298) 74.4 80.4 78.1 61.5 76.3 82.8 79.7 76.3

22. Baseline Predictors for Use of ≥ 3 of 4 Medication Classes in the US Secondary Prevention Population 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3). OR, 4.59; P < 0.0001 OR, 1.76; P < 0.0001 OR, 1.62; P < 0.0001 OR, 1.55; P < 0.0001 OR, 1.40; P < 0.0001 OR, 1.27; P < 0.0001 OR, 1.22; P = 0.0029 OR, 1.22; P = 0.0072 OR, 1.19; P < 0.0001 OR, 1.14; P = 0.0063 OR, 1.13; P = 0.0044 OR, 0.79; P = 0.0095 OR, 0.86; P = 0.0014 OR, 0.86; P = 0.0001 OR, 0.82; P < 0.0001 OR, 0.81; P < 0.0001 OR, 0.78; P = 0.0060 OR, 0.71; P < 0.0001 OR, 0.68; P < 0.0001 OR, 0.60; P < 0.0001

23. Conclusions Guideline-recommended primary and secondary preventive therapies were underused across US census regions and physician specialties Among US Census regions, patients in the Northeast showed the highest use of preventive medication use, the South the lowest Among physician specialties, cardiologists showed the highest prescription of preventive medication use To improve use of guideline-recommended primary and secondary prevention, novel physician- and patient-centered approaches may be necessary 1.Kumar A et al, on behalf of the REACH Registry Investigators. Crit Pathw Cardiol 2009;8(3).

24. Participating organizations The REACH Registry is sponsored jointly by and endorsed by

25. For further information on the REACH Registry go to: http://www.REACHRegistry.org