Opportunistic Genetic Testing for Familial Hypercholesterolemia in Premature Acute Coronary Syndrome

BACKGROUND: Familial hypercholesterolemia (FH) is common among patients with premature acute coronary syndrome (ACS) but remains underdiagnosed and undertreated. OBJECTIVES: The ACCURATE (Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia) study evaluated whether opportunistic genetic testing in patients with premature ACS increases FH diagnosis and lipid-lowering therapy use. METHODS: ACCURATE was a nonrandomized, prospective study that recruited 2 sequential cohorts of patients. In phase 1, patients were treated according to usual standard of care, with no genetic testing. In phase 2, patients underwent FH genetic testing with results returned to treating physicians. Eligible patients were <60 years old admitted with ACS and had low-density lipoprotein cholesterol (LDL-C) ≥4 mmol/L (≥155 mg/dL). The primary endpoint was a new diagnosis of definite FH at 15 months post-ACS. Secondary endpoints were changes in lipid-lowering therapy and lipid levels. RESULTS: Overall, 40 patients in phase 1 and 100 patients in phase 2 completed the study, with similar baseline characteristics. A diagnosis of definite FH at follow-up occurred in 10% of patients in phase 2 vs 0% in phase 1. At 15 months, patients in phase 2 were more likely to achieve an LDL-C <1.8 mmol/L (73% vs 53%, P = 0.04), had lower mean LDL-C (1.65 mmol/L vs 1.93 mmol/L [64 mg/dL vs 75 mg/dL]) (P = 0.03), and were more likely to be receiving statin therapy (95% vs 83%, P = 0.04) or statin-ezetimibe combination therapy (52% vs 30%, P = 0.02). CONCLUSIONS: Opportunistic genetic testing of young adults with ACS was associated with increased FH diagnosis, more intensive lipid-lowering treatment, and improved lipid target attainment. (Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia [ACCURATE]; NCT05218005).