1. Date of download: 9/18/2016 Copyright © The American College of Cardiology. All rights reserved. From: Next Steps in Primary Prevention of Coronary Heart Disease: Rationale for and Design of the ECAD Trial J Am Coll Cardiol. 2015;66(16):1828-1836. doi:10.1016/j.jacc.2015.08.857 Figure Legend: Reductions in CHD Annual Event Rates Achieved by Decreased Serum LDL-C Level in 4 Major Prevention Trials of Statin Therapy Results of 4 major trials of LDL-C lowering, the ARIC study of LDL-C in carriers and noncarriers of the PCSK9 gene, and an illustrative hypothetical outcome of ECAD. Each of the trials demonstrated a reduction in event rate with pharmacological lowering of LDL-C. In the ARIC study, white participants had higher annual CHD event rates than black participants. Furthermore, in both ethnic groups, carriers of nonsense mutations in the PCSK9 gene (who have substantially reduced serum LDL-C concentrations) demonstrated a greatly reduced annual CHD event rate. The greater slope of the ARIC PCSK9 data, compared with prior clinical trials, suggests that the reduction in events is greater for a particular LDL-C level when that lower LDL-C is present throughout life than if it is effected much later, as occurred in the completed primary prevention trials. The hypothesized outcome of the ECAD trial would be interpreted as having started LDL-C lowering early enough to have gained most of the event-lowering effect that would have been achieved by maintaining similarly low levels from birth. Adapted with permission from Domanski et al. (1).

2. Date of download: 9/18/2016 Copyright © The American College of Cardiology. All rights reserved. From: Next Steps in Primary Prevention of Coronary Heart Disease: Rationale for and Design of the ECAD Trial J Am Coll Cardiol. 2015;66(16):1828-1836. doi:10.1016/j.jacc.2015.08.857 Figure Legend: Prevention of Coronary Heart Disease: ECAD Trial Flow diagram showing the design of the ECAD (Eliminate Coronary Artery Disease) trial. BP = blood pressure; CHD = coronary heart disease; LDL = low-density lipoprotein; MI = myocardial infarction.

3. Date of download: 9/18/2016 Copyright © The American College of Cardiology. All rights reserved. From: Next Steps in Primary Prevention of Coronary Heart Disease: Rationale for and Design of the ECAD Trial J Am Coll Cardiol. 2015;66(16):1828-1836. doi:10.1016/j.jacc.2015.08.857 Figure Legend: Estimation of the Additional Number of Patients Who Would Receive Statin Treatment if ECAD Shows an Advantage of Treating Younger Patients With Statins NHANES data were used for the calculations. ALT = alanine transaminase; ASCVD = atherosclerotic cardiovascular disease; AST = aspartate transaminase; CVD = cardiovascular death; DM = diabetes mellitus; GFR = glomerular filtration rate; HTN = hypertension; LR = likelihood ratio; NHANES = National Health and Nutrition Examination Survey; RF = risk factor; other abbreviations as in Figure 1.