Cardiology Resident Dalhousie University, Nova Scotia, Canada
Background: Familial hypercholesterolemia (FH) is the most common inherited cardiovascular condition that confers higher risk of development of atherosclerotic cardiovascular disease (ASCVD). An estimated 1 in 14 patients with premature (age < 60) acute coronary syndrome (ACS) have FH. However, most patients with FH remain undiagnosed with clinical criteria. The ACCURATE Study aims to assess the diagnostic yield and clinical utility of opportunistic genetic testing for patients with premature ACS. Here we present results from the standard-of-care arm (Phase 1).
METHODS AND RESULTS: ACCURATE is a multi-site, prospective, non-randomized clinical trial that includes patients < 60 years of age admitted to a cardiac care unit with ACS and LDL-C level ≥4 mmol/L, or LDL-C level ≥2.5 mmol/L if already on a statin. Phase 1 included 40 patients recruited from January to September 2022 who were treated according to usual standard-of-care (i.e. with no genetic testing for FH). During phase 2 (October 2022 to May 2024), 100 patients met inclusion criteria and underwent genetic testing and had results returned to the provider within one month of discharge. The primary endpoint was the number of patients with a new diagnosis of FH following discharge after ACS, based on the Dutch Lipid Clinic Network Score (DLCNS) or the Canadian Definition of FH. Secondary endpoints were the number of patients that underwent lipid lowering therapy intensification, the lowest LDL-C achieved, and the proportion of patients that achieved recommended lipid targets at the one-year interval as per Canadian Cardiovascular Society (CCS) 2021 guidelines (LDL-C < 1.8 mmol/L, non-HDL-C < 2.4 mmol/L, or apoB < 0.7 g/L). Baseline patient characteristics and comorbidities as well as lipid profiles within one year of or at the time of presentation are listed in Table 1. At follow up, 5% of patients in Phase 1 had a new clinical diagnosis of FH. Lipid lowering therapy was intensified in 30% of patients, and 49% achieved an LDL-C of < 1.8 mmol/L with a mean LDL of 1.9 mmol/L (representing a 54% reduction from baseline, p < 0.01) in Phase 1 at 12 months post-ACS follow-up (Table 2).
Conclusion: Few patients with premature ACS receive a clinical diagnosis of FH. Less than half of the patients in our study in Phase 1 met guideline-recommended lipid targets at the one-year interval. The ACCURATE trial will assess whether genetic testing increases the rate of diagnosis, and if this impacts patient care and mitigates the risk of recurrent cardiovascular events.
