Coronary artery calcium testing: exploring the need for a randomized trial.

C oronary artery calcium (CAC) imaging with noncontrast cardiac computed tomography has emerged as a robust method to reclassify atherosclerotic cardiovascular disease (ASCVD) risk. 1 Rigorously conducted observational studies have consistently demonstrated marked increases in ASCVD events in those with elevated CAC. 2–4 In addition, the absence of CAC on cardiac computed tomographic imaging is common and defines a low-risk group who seem unlikely to benefit from ASCVD prevention pharmacotherapies. 5,6 There are also modest data demonstrating that CAC-based management leads to improvements in downstream risk factors (cholesterol , systolic blood pressure, and waist circumference). 7,8 Similarly, CAC may inform decision making in persons who have difficulty tolerating statin therapy or in those with personal aversion to lifelong statin therapy. 9 In this context, CAC imaging is endorsed by the American Heart Association and the American College of Cardiology to help reclassify ASCVD risk and guide statin allocation, particularly in persons in whom the patient–doctor risk discussion leads to treatment uncertainty. However, there are no adequately powered prospective clinical trials of CAC-guided ASCVD prevention therapy to inform these guideline recommendations. Indeed, there has never been a trial demonstrating that randomization to preventive therapy using a risk-based assessment (either by risk prediction equations, 11 novel biomarkers, 12 or by subclinical atherosclerosis imaging) leads to reduced ASCVD events. 13 Nonetheless, the limited data we do have suggest that CAC-based treatment allocation, specifically with statin therapy, may lead to improved clinical outcomes. 14 In the single-center St Francis Heart study, participants underwent CAC screening, and those with CAC >80th percentile for age and sex (n=1007) were randomized to placebo or atorvastatin 20 mg daily. Despite a clear trend toward benefit, the trial failed to show a statistically significant difference in the incidence of major cardiovascular events (6.9% versus 9.9%; P=0.08). 12 However, the trial was underpowered, and in an exploratory post hoc analysis, subjects with CAC score >400 obtained benefit from statin therapy (8.7% versus 15.0% event rate; P=0.046). Given that ASCVD enjoys such a large proportion of federal research funding, it is surprising that these encouraging initial results have not been confirmed in a larger, more adequately powered contemporary study. Unfortunately, despite a seemingly clear need, 15 attempts to fund a larger outcomes CAC study have been unsuccessful. The Value of Imaging In Enhancing the Wellness of Your Heart (VIEW) study proposed a multicenter CAC trial with ≤6 years of follow-up for …