A large clinical trial comparing two methods for identifying patients at risk of heart disease found no significant difference in preventing major cardiovascular events, but uncovered important clues about how patients actually take their medications. Researchers at Intermountain Medical Center studied whether using coronary artery calcium (CAC) measurements, a specialized CT scan that detects plaque buildup in arteries, could better guide statin therapy decisions than traditional risk factor assessment.

What Is Coronary Artery Calcium and Why Does It Matter?

Coronary artery calcium is a marker of atherosclerotic cardiovascular disease (ASCVD), the buildup of plaque in arteries that can lead to heart attacks and strokes. The CAC measurement uses a computed tomography scan to visualize and quantify the amount of calcium deposits in coronary arteries, providing a direct picture of plaque burden. This differs from traditional risk assessment, which relies on factors like age, cholesterol levels, blood pressure, smoking status, and diabetes to estimate heart disease risk.

The challenge cardiologists face is deciding which patients truly need statin therapy, medications proven to prevent atherosclerotic cardiovascular disease. For many people, especially younger individuals, the first sign of heart disease is a heart attack itself, suggesting current risk assessment tools may be missing high-risk patients.

How Did Researchers Compare These Two Approaches?

The CorCal Outcomes trial enrolled 5,772 patients with an average age of 64 years, of whom 51% were women. Participants had no known cardiovascular disease, diabetes, or prior statin therapy. Researchers randomly assigned patients to receive statin recommendations based on either the pooled cohort equations (PCE), which use traditional risk factors, or their CAC score.

After following patients for an average of 4.2 years, researchers tracked major cardiovascular events including all-cause mortality, heart attacks, strokes, and procedures to restore blood flow to arteries. The results were striking: major cardiovascular events occurred in 2.7% of patients in both groups, showing no meaningful difference between the two approaches.

What Were the Unexpected Findings About Medication Use?

While the two risk assessment methods produced similar outcomes, they revealed a dramatic difference in how patients actually used their medications. Patients assigned to the PCE group received recommendations to start statins more than three times as often as those in the CAC group. However, this higher recommendation rate did not translate to better outcomes.

The striking finding was medication adherence. Among patients who received a statin recommendation based on their CAC score, 62% actually took the medication as prescribed. In contrast, only 23% of patients recommended statins based on traditional risk factors stuck with their treatment. This suggests that when patients have a concrete, visual marker of disease, they may be more motivated to follow medical advice.

"For far too many patients, the first symptom of ASCVD is a heart attack. Statins have been shown to be highly effective in the prevention of ASCVD; however, there is a major gap in risk assessment, statin initiation and statin persistence," said Dr. Joseph B. Muhlestein, Principal Investigator of the CorCal Outcomes trial.

Dr. Joseph B. Muhlestein, Principal Investigator, CorCal Outcomes trial, Intermountain Medical Center

Why Didn't the Study Show a Clear Winner?

The researchers noted that cardiovascular events overall were lower than expected, which reduced the study's statistical power to detect a meaningful difference between the two approaches. This actually reflects good news: modern preventive care, including existing statin use and other treatments, has become more effective at preventing heart disease than in previous decades.

Despite not meeting the study's primary goal of proving noninferiority, the trial generated important insights. The data suggest that CAC scoring may be more efficient at identifying which patients truly need statins, while also improving medication adherence through the power of visual evidence of disease.

How to Use These Findings in Your Own Heart Health?

• Understand Your Risk Factors: Key modifiable risk factors for heart disease include smoking, diabetes, high blood pressure, and elevated cholesterol levels. Knowing your numbers and addressing these factors remains essential regardless of which assessment method your doctor uses.
• Ask About CAC Scoring: If you are at moderate risk for heart disease or near the threshold for statin therapy, discuss with your cardiologist whether a coronary artery calcium scan might provide additional clarity about your individual risk.
• Prioritize Medication Adherence: Whether your statin recommendation comes from traditional risk scores or a CAC scan, taking the medication as prescribed is crucial. The study showed that adherence matters more than the method used to make the initial recommendation.
• Discuss Your Concerns: If you receive a statin recommendation but feel uncertain, ask your doctor to explain your specific risk factors or consider requesting a CAC scan to visualize your coronary artery status.

The 2025 Focused Update of the European Society of Cardiology and European Atherosclerosis Society guidelines now recommend that if a CAC scan is performed, an increased score should be considered as a risk modifier in individuals at moderate risk or those near treatment decision thresholds.

"The study did provide important hypothesis-generating insights into the efficiency of statin initiation and adherence when decisions are based on CAC scoring. Taken together, our data could be used to plan an additional well-powered randomised trial comparing CAC with current risk factor-based algorithms," concluded Dr. Muhlestein.

Dr. Joseph B. Muhlestein, Principal Investigator, CorCal Outcomes trial, Intermountain Medical Center

The bottom line is that both approaches to assessing cardiovascular risk can work, but the choice between them may matter less than ensuring patients actually take their prescribed medications. The real opportunity lies in using whichever method best motivates individual patients to commit to their heart health, whether that is a concrete visual scan or a discussion of traditional risk factors. As cardiovascular disease remains the leading cause of death globally, improving both risk assessment and medication adherence remains a critical priority for preventing heart attacks and strokes.