Coronary Artery Calcium Score to Refine the Use of PCSK9i in Asymptomatic Individuals: A Multicohort Study

BACKGROUND: The value of coronary artery calcium (CAC) in the allocation of PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitors) among individuals without clinically evident atherosclerotic cardiovascular disease (ASCVD) is unknown for indications that do not require confirmed familial hypercholesterolemia. We aimed to assess the ability of CAC to stratify ASCVD risk under 3 non–familial hypercholesterolemia PCSK9i allocation paradigms. METHODS AND RESULTS: We included participants without clinically evident ASCVD from MESA (Multi‐Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults) study, DHS (Dallas Heart Study), and HNR (Heinz Nixdorf Recall) study. Three PCSK9i eligibility scenarios were defined: a broad scenario informed only by high low‐density lipoprotein cholesterol levels (N=567), a restrictive one combining higher low‐density lipoprotein cholesterol levels and presence of ≥2 additional risk factors (N=127), and a high‐risk scenario where individuals with subclinical organ damage or high estimated risk would be treated to achieve low‐density lipoprotein cholesterol <55 mg/dL (N=471). The high‐risk scenario had the highest ASCVD event rates (27.8% at 10 years). CAC=0 was observed in 35% participants in the broad scenario, 25% in the restrictive scenario, and 16% in the high‐risk scenario. In all, CAC=0 was associated with the lowest incident ASCVD rates at 5 and 10 years, and CAC burden was independently associated with ASCVD events adjusting for traditional risk factors. CONCLUSIONS: CAC may be used to refine the allocation of PCSK9i, potentially leading to a more conservative use if CAC=0. The value of CAC testing is greater in scenarios that use low‐density lipoprotein cholesterol levels and/or traditional risk factors to define PCSK9i eligibility (CAC=0 present in 1 of 3–4 patients), whereas its prevalence is lower when allocation is informed by presence of noncoronary subclinical organ damage.