Coronary Plaques Reined in With Coronary Calcium Scans in the Picture

For select risk-enhanced individuals at intermediate risk of coronary artery disease (CAD), researchers found a way to implement coronary artery calcium (CAC) scores and primary prevention statins together to slow the progression of atherosclerotic plaque.

In the CAUGHT-CAD randomized trial, measures of coronary plaque progression favored a strategy of CAC-informed lifestyle intervention with statin initiation in people with a family history of premature CAD. Compared with the CAC strategy, usual care was associated with worse plaque progression over 3 years:

• Total plaque volume: mean +24.9 mm³ vs +15.4 mm³ (P=0.009)
• Noncalcified plaque volume: mean +15.7 mm³ vs +5.6 mm³ (P=0.002)
• Fibrofatty and necrotic core plaque volume: mean +4.5 mm³ vs -0.8 mm³ (P=0.02)

While there was no between-group difference in calcified plaque volume (mean +8.9 mm³ vs +10.1 mm³, P=0.48), the larger picture still suggests that noninvasive CAC testing may benefit patients — even though the study was ultimately not designed to assess cardiac events, reported Thomas Marwick, MBBS, PhD, MPH, of Baker Heart and Diabetes Institute in Melbourne, Australia, and colleagues in JAMA.

“In individuals at intermediate risk of CAD with a family history of premature CAD, a practitioner-led, CAC score-informed lifestyle intervention with moderate-intensity statin therapy resulted in less progression of plaque parameters that are associated with future adverse cardiovascular risk,” they concluded.

The holy grail is still a trial showing proven event reductions to directly support CAC use.

The CAC score, a proxy measurement of subclinical atherosclerosis, relates to visual images that show the amount of calcium in one’s arteries. Without proof that CAC scoring really improves outcomes, guidelines moderately suggest using it as a risk arbiter in deciding whether to initiate statins in intermediate-risk patients.

“The CAUGHT-CAD trial challenges the solely risk factors-based approach to [atherosclerotic cardiovascular disease] prevention by placing subclinical coronary atherosclerosis at the center of the CVD prevention paradigm,” commented Khurram Nasir, MD, MPH, MSc, of Houston Methodist DeBakey Heart and Vascular Center, and Ron Blankstein, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston.

In an accompanying editorial, they highlighted the “upstream CAC score testing followed by targeted interventions in those with evidence of disease. This approach achieved near-universal statin initiation and high adherence, effectively bridging the gap between risk stratification and actionable care.”

CAUGHT-CAD was a randomized trial conducted in seven Australian hospitals. Participants were 365 asymptomatic adults ages 40-70 with a first-degree relative with CAD onset before age 60 (or second-degree relative with onset before age 50). Marwick’s team had statin-naive participants undergo an initial CT, and CAC scores above 0 and below 400 sent them to confirmatory coronary CT angiography.

Those randomized to the CAC-informed strategy were shown their CAC pictures during a nurse-led education session, and they were prescribed lipid-lowering therapy, namely atorvastatin (Lipitor) 40 mg. Controls, on the other hand, received standard CVD prevention education and guideline-based risk management from their general practitioners who were unaware of their CAC score.

Those with a baseline CAC of 100 or greater were especially likely to show improved plaque progression following a CAC-informed prevention intervention, according to Marwick and colleagues.

“This finding is consistent with prior research suggesting that individuals with CAC scores greater than 100 are likely to derive substantial benefit from lipid-lowering, aspirin, and emerging cardiometabolic therapeutics,” Nasir and Blankstein noted.

“Importantly, CAC testing has been shown to improve adherence and lifestyle interventions, and appears to be cost-effective,” according to the duo.

Despite its promise, widespread adoption is hindered, as CAC testing for asymptomatic individuals is not covered by Medicare and is typically not covered by private insurance. Some hospitals and medical centers have lowered their charges for CAC scans to the $50 to $100 range.

Michael Blaha, MD, MPH, of Johns Hopkins University School of Medicine in Baltimore, said he expected the next iteration of the guidelines to reflect the growing knowledge about CAC.

“Most practicing clinicians and most patients do not find an indiscriminate treat-all scenario to be compelling or realistic. In the primary prevention space, an enormous amount of time is spent discussing statins with patients, and statin skepticism remains highly prevalent and long-term adherence to therapy remains very low,” Blaha noted in his own editorial, published in JAMA Cardiology.

“CAC testing is extremely appealing as a primary prevention strategy to personalize risk assessment and individualize the intensity of preventive therapy. This is because the test is widely available, fast, highly reproducible, low radiation, directly reflective of total coronary plaque burden, and highly predictive of future atherosclerotic cardiovascular disease events,” according to Blaha.

The CAUGHT-CAD cohort averaged 58 years of age, with 57.5% men. Mean 10-year risk according to the pooled cohort equation was 6.6% in the CAC-informed group and 7.2% among controls. Baseline CAC scores were a median 35 vs 32, respectively, and about a quarter of people had CAC scores of 100 or greater.

Differences in plaque volume were independent of risk factors including baseline plaque volume, blood pressure, and lipid profile.

Although the study was not powered for secondary analyses, there was a tally of clinical events: the CAC-strategy group counted two atrial fibrillation events and two percutaneous interventions for angina throughout follow-up, whereas usual care was linked to one transient ischemic attack, one pacemaker insertion, one myocardial infarction, and two percutaneous interventions for angina.

Marwick and colleagues acknowledged CAUGHT-CAD’s open-label design. There were also plenty of CT image quality issues resulting in 13% of patients getting excluded because of them. The 365 participants were those who stayed in the study and had viable CAC images out of 449 people randomized initially.

It also remains to be seen whether CAC testing should be applied beyond intermediate-risk middle-age adults for primary prevention.

“A dilemma remains about young adults (age <40 years in men or <50 years in women). These individuals might have the most to gain from early risk factor intervention, but the least motivation to adhere to aggressive lifelong medical therapy,” Blaha wrote.

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