Practice Point: Patients at intermediate risk of cardiovascular disease events and with a family history of premature coronary artery disease might benefit from statins and blood pressure control, without a compelling reason to add a coronary artery calcium (CAC) score (yet).
EBM Pearl: Surrogate markers such as total coronary plaque volume may not directly translate into improved clinical outcomes and shouldn’t be used in isolation to make clinical decisions.
A big debate in cardiology is when to start primary preventive medication in people with a family history of premature coronary artery disease (CAD) when they themselves have intermediate risk. Keep in mind, of course, that the NNT to prevent one additional death in someone with a 10 percent 10-year risk of cardiovascular disease (CVD) events is about 500.
The CAUGHT-CAD trial published in JAMA purports to be an assessment of whether CAC-informed care lowers the risk of atherosclerotic plaque progression in intermediate-risk patients with a family history of early CAD. The authors evaluated adults aged 40-70 years (mean age 58 years) with a CAC score of 1-399 who were statin-naïve and asymptomatic. Patients were deemed “intermediate risk” based on the AusCVD score, which is an Australian version of the Framingham risk score. (The trial was conducted across seven hospitals in Australia.) ASCVD risk was also assessed using the United States-based 10-year pooled cohort equation with a mean risk of 6.6-7.2 percent for all participants, which, when tallied with the risk-enhancing family history of premature CVD, also placed everyone in the intermediate-risk category.
Participants were randomized to either CAC score-informed care or usual care and were evaluated by coronary CT at baseline and at three years. CAC-informed care included statin therapy (initiated at 40 mg atorvastatin for everyone in this arm), blood pressure management, and a standardized nurse-based intervention with education about self-management and lifestyle, care coordination, and risk modification. Usual care included standard education on CAD prevention and risk management, and although none were initially started on lipid-lowering therapy, nine of the 186 participants eventually received statin therapy, albeit usually at a lower than 40 mg atorvastatin equivalent.
Results showed that the CAC-informed care group had decreased plaque volume, total cholesterol, and low-density lipoprotein cholesterol compared to the usual care group at three years.
One of the biggest problems with this study is that the primary outcome (change in total plaque volume) was a surrogate outcome, without any clinical outcomes such as death or CVD events reported. Surrogate markers are often cheaper, easier, and more quantifiable to study but don’t always predict clinical outcomes.
Another major problem was the layered intervention. The CAC-informed care group might as well have been called the “primary prevention group” because it consisted of statin initiation, blood pressure management, and knowledge of CAC score in addition to “usual care.” At the last check, statins and blood pressure management are usual care for people at or above intermediate risk (in the United States anyway). As far as meaningful interventions go, this one is pretty hollow.
So, while the study authors claim they aimed to evaluate the benefit of CAC scores for patients with a family history of early CAD, we wonder if the real impetus was to find a use for CAC scores, which have not been as widely embraced as perhaps some thought (hoped?) they might be. Regardless of the study’s intent, its design, execution, and results suggest there is still no clear clinical evidence of any added benefit of a CAC score to “usual” care.
For more information, see the topic Coronary Artery Calcium (CAC) Scoring and Clinical Use in DynaMedex.
Reference: JAMA. 2025 Mar 5 early online
