OBJECTIVES: This study aimed to assess if information on CAD severity from coronary computed tomography angiography (CTA) can identify patients that benefit most from treating low-density lipoprotein-cholesterol (LDL-C) to American Heart Association/American College of Cardiology (ACC/AHA) and European Society of Cardiology (ESC) guidelines targets. BACKGROUND: Current treatment guidelines for secondary prevention of atherosclerotic cardiovascular disease (ASCVD) disregard severity of coronary artery disease (CAD) for treatment choices. It is unclear whether severity of CAD should be considered in treatment recommendations. METHODS: Among 20,241 symptomatic patients undergoing diagnostic CTA from the Western Denmark Heart Registry, we assessed the number needed to treat (NNT) in 6 years to prevent 1 ASCVD event as well as the proportion of all events that could be prevented by treating LDL-C to targets. We assumed a 22% relative reduction of ASCVD events per 1 mmol/l reduction in LDL-C. RESULTS: In multivariable analysis with no CAD as the reference, the subdistribution hazard ratio for ASCVD events was 4.0 (95% confidence interval [CI]: 3.3 to 4.9) for 1-vessel disease, 4.6 (3.5 to 6.0) for 2-vessel disease, and 5.6 (4.0 to 8.0) for 3-vessel disease. Consequently, the NNT to prevent 1 ASCVD event in 6 years by treating LDL-C to targets varied greatly from 233 (ESC) and 110 (ACC/AHA) for patients with no CAD to 8-9 for patients with 3-vessel disease (both ACC/AHA and ESC). The estimated percentage of ASCVD events that could be prevented by achieving guideline targets was 30% to 36% for patients with obstructive disease. However, <20% of patients achieved targets. CONCLUSIONS: An individualized approach based on CAD severity can identify symptomatic patients that are likely to derive most and least benefit from treating LDL-C to ACC/AHA and ESC treatment targets.