Statin Therapy in HIGH-Risk Individuals with NORMal Coronary Arteries: The HIGH-NORM Study

Aims: Mismatches between the risk status of a patient and coronary imaging data can lead to conflicting strategies to prevent a cardiovascular event. We evaluated whether statin use was associated with cardiovascular benefit in high-risk individuals whose coronary computed tomography angiography (CCTA) results showed normal coronary arteries. Methods: Among asymptomatic individuals whose CCTA showed normal or near normal coronary arteries, 3,389 persons with high- or very-high-risk status were included in this retrospective study. After 1:2 propensity score matching, 906 individuals (302 new statin users and 604 controls; mean age 61 years; male 58%) were analysed. The primary outcome variable was major adverse cardiovascular and cerebrovascular events (MACCEs) that consisted of cardiovascular death, nonfatal myocardial infarction, coronary revascularisation, and nonfatal ischemic stroke. Results: At a median follow-up of 5.8 years, 20 statin users and 17 controls (7.4 and 5.6 events/1,000 person-year, respectively; hazard ratio [HR) 1.04; p = 0.92) experienced MACCE. Kaplan-Meier curves showed similar MACCE rates in both groups (p = 0.91). In separate analyses for persons with normal (p = 0.29) or near normal coronary arteries (p = 0.67), MACCE rates did not differ between the groups. Age (HR 1.04; p = 0.044), male sex (HR 3.06, p = 0.018), and smoking (HR 2.87, p = 0.019) were independently associated with MACCEs. In subgroup analyses, no significant factors affected the relationship between statin use and MACCEs. Conclusions: Statin use was not associated with cardiovascular risk reduction in high-risk persons with normal or near normal coronary arteries. More individualised lipid-lowering therapy may benefit this population.