1. The SHAPE Trial Advisory Meeting – Part II GoToMeeting Session Monday Nov 9 th, 12PM EST https://global.gotomeeting.com/join/580198429 Dial +1 (312) 757-3121 Access Code: 580-198-429 Meeting Password: SHAPE11https://global.gotomeeting.com/join/580198429 Followed by Focus Group Meeting as a satellite event in conjunction with Annual Scientific Sessions of American Heart Associations November 9, 7-9PM (Dinner), Rosen Plaza Hotel, Salon 12 Orlando, Florida

2. Comparative Effectiveness Trial Designs of Coronary Artery Calcium Screening vs. Risk Estimation Presenter: David Maron, M.D. Professor and Director, Preventive Cardiology Stanford University School of Medicine, Stanford, CA

3. Trial Designs VIEW ROBINSCA original www.robinsca.nlwww.robinsca.nl Modified ROBINSCA with a CAC zero PRECISION SCORE 1 SCORE 2

4. VIEW N=30,000

5. ROBINSCA N=39,000 at high risk for CAD based on a questionnaire and self-measured waist circumference N=13,000 MD discretionACEi + statin What about CAC =0?

6. Asymptomatic Smokers* Undergoing Low Dose CT for Early Lung Cancer Screening and CAC >400 Primary Prevention Strategy (“Usual Care”) Secondary Prevention Strategy (“Directed Care”) MD Discretion PRECISION Follow-up for outcomes MD Discretion *55-74 years old with Hx cigarette smoking >30 pack-years; if former smoker, must have quit within the previous 15 years

7. Asymptomatic Smokers Undergoing Low Dose CT for Early Lung Cancer Screening and CAC >400 or 0 Blinded to Score ASCVD Risk Estimate Unblinded Score MD Discretion Usual Care High-intensity statin and aspirin No statin or aspirin SCORE 1 Screening Calcium or Risk Estimation CAC >400 CAC = 0 Follow-up for outcomes

8. Consent all asymptomatic smokers undergoing low dose CT for early lung cancer screening and randomize only CAC >400 to aggressive Rx No Score, use ASCVD Risk Estimate Unblinded Score >400 Usual Care, annual assessment (email) High-Intensity Statin and aspirin SCORE 2 (Berman) Screening Calcium or Risk Estimation Follow-up for outcomes Perform CAC scoring at end of trial, assess >400 group

9. ROBINSCA N=39,000 at high risk for CAD based on a questionnaire and self-measured waist circumference N=13,000 MD discretionACEi + statin

10. David Maron’s Questions to ROBINSCA Investigators: 1) Is statin recommended or provided? If provided, only for group B, or for A and B? 2) Is statin dose the same regardless of calcium score? 3) Could statin be changed from simvastatin to atorvastatin (because of greater efficacy, fewer drug-drug interactions)? 4) How do you manage CAC = 0? Rx statin or withhold statin? 5) Is low dose aspirin recommended to everyone with CAC >0?

11. Questions for brainstorming at SHAPE Trial Advisory Meeting Part-2: A) if ROBINSCA is completed today and shows superiority of CAC-based risk assessment, will it be sufficient to change (AHA/ACC/ESC) guidelines, get FDA/CMS/USPTFS endorsement, and convince the payers, or will we need additional studies? B) if ROBINSCA is completed today and shows lack of superiority for CAC-based risk assessment, will it be sufficient to negate other evidence gathered so far, including HRP, MESA, HNR, etc.? C) How do we go about testing carotid and possibly femoral plaque measurement with ultrasound in these trials? is the combination of CAC and US useful as shown by HRP/BioImage? How about functional testing and monitoring response to therapy? Other questions are welcomed.

12. View discussions of SHAPE Trial Advisory Meetings Part 1 and 2 www.shapesociety.org