medwireNews: Using coronary artery calcium (CAC) scoring to inform a primary prevention program for intermediate-risk familial coronary artery disease (CAD) may help reduce atherosclerotic plaque progression compared with usual care, according to the results of a randomized controlled trial.
In the CAUGHT-CAD trial, the mean total plaque volume determined using coronary computed tomography angiography (CCTA) was similar at baseline among those who were assigned to receive a CAC score-informed primary prevention program (n=179) or to receive usual care (n=186), at a respective 116.9 and 115.7 mm3.
However, at 3 years, the total plaque volume had increased to a significantly lesser degree in the CAC score-informed than the usual care group, at a respective 132.33 mm3 and 140.6 mm3, with mean increases from baseline of 15.4 versus 24.9 mm3.
Notably, the CAC score-informed prevention program was associated with significantly less progression from baseline of both noncalcified plaques (5.6 vs 15.7 mm3), and fibrofatty and necrotic core (–0.8 vs 4.5 mm3) plaques.
“These plaque volume changes were independent of other risk factors including baseline plaque volume, blood pressure, and lipid profile,” write Thomas Marwick (Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia) and fellow investigators in JAMA.
They report significantly greater mean sustained reductions with CAC score-informed versus usual care in total cholesterol (TC, 56 vs 3 mg/dL) and low-density lipoprotein cholesterol (LDL-C, 51 vs 2 vs mg/dL). This contributed to a lower estimated 10-year cardiovascular risk of 0.5% versus 2.1%.
Marwick et al screened more than 1000 people aged between 40 and 70 years who had a first-degree relative with CAD diagnosed before the age of 60 years or a second-degree relative diagnosed with CAD before the age of 50 years. None met the standard criteria for statin use due to having TC levels below 250 mg/dL [6.5 mmol/L] and LDL-C levels below 193 mg/dL [5.0 mmol/L].
Of these individuals, 365 (mean age 58 years, 57.5% men) were deemed at intermediate risk for developing CAD (annualized rate of 0.4–3.0%), according to an Australian risk calculator, and progressed to CAC scoring. Those with scores between 0 and 400 points (mean 64.0–72.6 points) – indicating no plaque up to a moderate amount of plaque – then underwent CCTA.
CCTA with CAC scoring was subsequently performed at 6-month intervals, but the results were only shown to those in the CAC score-informed group as part of a nurse-led primary prevention program. This involved self-management education, care coordination, and risk modification, and resulted in all patients in the CAC score-informed group receiving lipid-lowering therapy (atorvastatin 40 mg) in addition to standard blood pressure control.
By contrast, participants in the usual care group received standard education on lifestyle and CAD prevention, and as-needed guideline-based risk management via their primary care practitioner, with just nine patients prescribed atorvastatin or rosuvastatin over the 3-year follow-up.
People with CAC scores below 100 points (suggesting some plaque) experienced significant benefit from CAC score-informed care in terms of the progression in noncalcified plaque volume, but it was only when the CAC score increased above this threshold that there were also significant treatment differences versus usual care in the progression of total, and fibrofatty and necrotic core plaque volumes.
With regard to safety, statin use was withdrawn in 27 people in the CAC score-informed group but there were no reports of major statin side effects such as muscle weakness or acute hepatitis, say the researchers. The most common reasons for withdrawal were myalgia, gastrointestinal discomfort, or nonadherence.
There were four reported transient adverse events of rash and hypotension reported during CCTA, although none of the patients needed hospital treatment or subsequent therapy.
Nine cardiac events were reported, including two atrial fibrillation episodes and two percutaneous interventions for angina in the CAC score-informed group, and one transient ischemic attack, one pacemaker insertion, one myocardial infarction, and two percutaneous interventions for angina in the usual care group.
In one of two editorials accompanying the publication, Michael Blaha (Johns Hopkins University School of Medicine, Baltimore, Maryland, USA) says that these data have been “long-awaited.”
He observes that “CAUGHT-CAD suggests that the best way of predicting plaque progression toward an [atherosclerotic cardiovascular disease] event is to start with a simple baseline measure of plaque burden to ‘risk enhance’ the potential treatment population, independent of risk factor values.”
In the second editorial, Khurram Nasir (Houston Methodist, Texas, USA) and Ron Blankstein (Brigham and Women’s Hospital, Boston, Massachusetts, USA) call CAUGHT-CAD “a landmark trial,” and say that the “findings challenge reliance on current risk score-based framework for [cardiovascular disease] prevention.”
They suggest that the trial “offers a compelling middle-ground alternative” between no treatment and a treat all approach, by utilizing “upstream CAC score testing followed by targeted interventions in those with evidence of disease.”
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JAMA 2025; doi:10.1001/jama.2025.0584
JAMA 2025; doi:10.1001/jamacardio.2025.0410
JAMA 2025; doi:10.1001/jama.2025.2323
