Key takeaways
Statins are highly effective at preventing atherosclerotic cardiovascular disease but selecting which patients are most at risk and should receive statins can be challenging.
The CorCal Outcomes trial compared whether statin initiation based on the patient's coronary artery calcium measurement could reduce cardiovascular events vs. traditional risk factor-based assessment.
No difference was observed in major cardiovascular events with coronary artery calcium or risk factor assessment.
Cardiovascular events overall were lower than expected, limiting the trial's power, but insights could be used to plan further studies to improve on current risk assessment.
Munich, Germany – 31 August 2026: There was no difference in major cardiovascular events when statin initiation was based on coronary artery calcium compared with traditional risk factor assessment, according to results presented in a Hot Line session today at ESC Congress 2026.1
Cardiovascular diseases continue to be the leading cause of morbidity and mortality globally. The leading contributor to the cardiovascular disease burden is atherosclerotic cardiovascular disease (ASCVD), which includes coronary artery disease and ischaemic stroke. Key modifiable risk factors for ASCVD include smoking, diabetes, hypertension and high cholesterol levels.
"For far too many patients, the first symptom of ASCVD is a heart attack," said Doctor Joseph B Muhlestein from the Intermountain Medical Center, Murray, USA, the Principal Investigator of the CorCal Outcomes trial. "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." He noted that for a high percentage of individuals, especially younger individuals with a first heart attack, current risk assessment tools would not have identified them as being at sufficiently high risk to warrant statin therapy.
The CorCal Outcomes trial compared two methods for selecting patients to receive statin therapy to prevent a first cardiovascular event: the pooled cohort equations (PCE), which are based on traditional risk factors, and coronary artery calcium (CAC) measurement, which is an assessment of coronary plaque burden performed using a computed tomography (CT) scan.
Patients without known ASCVD, diabetes or prior statin therapy who were registered with the Canyons and Desert regions of Intermountain Health Care, USA, were invited to participate. Eligible patients were randomised (1:1) to receive guidance on statin initiation based on either their PCE risk score or their CAC score. The participants and their physicians received a protocol-directed recommendation on whether to initiate statin therapy based on the results and they made the final treatment decisions. The primary endpoint was major cardiovascular events (MACE; all-cause mortality, myocardial infarction, stroke and arterial revascularisation). The study population comprised 5,772 patients who had a mean age of 64 years and 51% were women.
After 4.2 years of follow-up, there was no difference in MACE between the groups. MACE occurred in 2.7% of patients in both groups and the noninferiority criterion was not met (hazard ratio 0.99; 95% confidence interval 0.71 to 1.38; p=0.045 for noninferiority).
The researchers found that patients randomised to the PCE group received a recommendation to initiate statins more than three times as frequently as those in the CAC group. However, patients who were recommended a statin based on their CAC score were much more adherent with their medication than those in the PCE group (62% vs. 23%).
"The power of the study to detect a difference was reduced by the lower-than-expected event rates and we did not demonstrate noninferiority between the groups," said Doctor Muhlestein, who concluded: "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."
The 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias include a recommendation that the presence of subclinical atherosclerosis by increased CAC score, if measured, should be considered as a risk modifier in individuals at moderate risk or individuals around treatment-decision thresholds.2
