Background: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines recommend primary prevention with statins for individuals with ≥7.5% 10-year risk for atherosclerotic cardiovascular disease (ASCVD). Everyone living long enough will become eligible for risk-based statin therapy due to age alone.

Objectives: This study sought to personalize ACC/AHA risk-based statin eligibility using noninvasive assessment of subclinical atherosclerosis.

Methods: In 5,805 BioImage participants without known ASCVD at baseline, those with ≥7.5% 10-year ASCVD risk were down-classified from statin eligible to ineligible if imaging revealed no coronary artery calcium (CAC) or carotid plaque burden (cPB). Intermediate-risk individuals were up-classified from optional to clear statin eligibility if CAC was ≥100 (or equivalent cPB).

Results: At a median follow-up of 2.7 years, 91 patients had coronary heart disease and 138 had experienced a cardiovascular disease event. Mean age of the participants was 69 years, and 86% qualified for ACC/AHA risk-based statin therapy, with high sensitivity (96%) but low specificity (15%). CAC or cPB scores of 0 were common (32% and 23%, respectively) and were associated with low event rates. With CAC-guided reclassification, specificity for coronary heart disease events improved 22% (p < 0.0001) without any significant loss in sensitivity, yielding a binary net reclassification index (NRI) of 0.20 (p < 0.0001). With cPB-guided reclassification, specificity improved 16% (p < 0.0001) with a minor loss in sensitivity (7%), yielding an NRI of 0.09 (p = 0.001). For cardiovascular disease events, the NRI was 0.14 (CAC-guided) and 0.06 (cPB-guided). The positive NRIs were driven primarily by down-classifying the large subpopulation with CAC = 0 or cPB = 0.

Conclusions: Withholding statins in individuals without CAC or carotid plaque could spare a significant proportion of elderly people from taking a pill that would benefit only a few. This individualized disease-guided approach is simple and easy to implement in routine clinical practice.