Preventing ASCVD Events: Using Coronary Artery Calcification Scores to Personalize Risk and Guide Statin Therapy

The question of whether individuals undergoing LCS with LDCT who have no detectable CAC can avoid statin therapy is an unresolved issue; no contemporary studies have looked specifically at the relationship between estimated risk, a CAC score of 0, and ASCVD outcomes in individuals participating in LCS. For these reasons, we recommend moderate-intensity statin therapy when the estimated risk is intermediate because it is unclear that either an Agatston score of 0 reclassifies intermediate-risk LCS-eligible individuals to a lower risk group.

For the few borderline risk (estimated risk, 5% to < 7.5%) LCS-eligible individuals, a CAC score of 0 might confer low short-term risk but the long-term benefit of statin therapy on reducing subsequent risk, the presence of other risk factors, and the willingness to stop smoking should all be considered. For these individuals who elect to avoid statin therapy, annual re-estimation of risk at the time of repeat LDCT is recommended. In these circumstances, referral for traditional Agatston scoring is not likely to change decision making because the sensitivity of the 2 techniques is very similar.

Agatston Score of 1-99 or CAC-DRS or Visual Score of 1

In general population studies, these scores correspond to borderline risk and an estimated 10-year event rate of just under 7.5%.²⁰ In both the NELSON and NLST LCS trials, even low amounts of CAC regardless of the scoring method were associated with higher observed ASCVD mortality when adjusted for other baseline risk factors.³² Thus, in patients undergoing LCS with intermediate and borderline risk, a CAC score between 1 and 99 or a visual estimate of 1 indicates the presence of subclinical atherosclerosis, and moderate-intensity statin therapy is reasonable.

Agatston Score of 100-299 or CAC-DRS or Visual Score of 2

Across all ages, races, and sexes, CAC scores between 100 to 299 are associated with an event rate of about 15% over 10 years.²⁰ In the NELSON LCS trial, the adjusted hazard ratio for ASCVD events with a nontraditional Agatston score of 101 to 400 was 6.58.³³ Thus, in patients undergoing LCS with a CAC score of 100 to 299, regardless of the baseline risk estimate, the projected absolute event rate at 10 years would be about 20%. Moderate-intensity statin therapy is recommended to reduce the baseline LDL-C by 30% to 49%.

Agatston Score of > 300 or CAC-DRS or Visual Score of 3

Agatston CAC scores > 300 are consistent with a 10-year incidence of ASCVD events of > 15% regardless of age, sex, or race and ethnicity.²⁰ In the Calcium Consortium, a CAC > 400 was correlated with an event rate of 13.6 events/1000 person-years.¹² In a Walter Reed Military Medical Center study, a CAC score > 400 projected a cumulative incidence of ASCVD events of nearly 20% at 10 years.³⁴ In smokers eligible for LCS, a CAC score > 300 projected a 10-year ASCVD event rate of 25%.²⁹ In these patients, moderate-intensity statin therapy is recommended, although high-intensity statin therapy can be considered if there are other risk factors.

Agatston Score ≥ 1000

The 2018 consensus statement on CAC reporting categorizes all CAC scores > 300 into a single risk group because the recommended treatment options do not differ.¹⁹ However, recent data suggest this might not be the case since individuals with very high CAC scores experience high rates of events that might justify more aggressive intervention. In an analysis of individuals who participated in the CAC Consortium with a CAC score ≥ 1000, the all-cause mortality rate was 18.8 per 1000 person-years with a CV mortality rate of 8 per 1000 person-years.³⁵ Individuals with very high levels of CAC > 1000 also have a greater number of diseased coronary arteries, higher involvement of the left main coronary artery, and significantly higher event rates compared with those with a CAC of 400 to 999.³⁶ In an analysis of individuals from the NLST trial, nontraditionally measured Agatston score > 1000 was associated with a hazard ratio for coronary artery disease (CAD) mortality of 3.66 in men and 5.81 in women.¹⁷ These observed and projected levels of risk are like that seen in secondary prevention trials, and some experts have recommended the use of high-intensity statin therapy to reduce LDL-C to < 70 mg/dL.³⁷

Primary Prevention in Individuals aged 76 to 80 years

LCS can continue through age 80 years, while the PCE and primary prevention guidelines are truncated at age 75 years. Because age is a major contributor to risk, many of these individuals will already be in the intermediate- to high-risk group. However, the net clinical benefit of statin therapy for primary prevention in this age group is not well established, and the few primary prevention trials in this group have not demonstrated net clinical benefit.³⁸ As a result, current guidelines do not provide specific treatment recommendations for individuals aged > 75 years but recognize the value of shared decision making considering associated comorbidities, age-related risks of statin therapy, and the desires of the individual to avoid ASCVD-related events even if the net clinical benefit is low.

Older individuals with elevated CAC scores should be informed about the risk of ASCVD events and the potential but unproven benefit of moderate-intensity statin therapy. Older individuals with a CAC score of 0 likely have low short-term risk of ASCVD events and withholding statin therapy is not unreasonable.