Discontinuation of lipid-modifying agents and failure to achieve target LDL cholesterol levels across cardiovascular risk groups

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) control remains suboptimal, with limited evidence on how adherence to lipid-modifying agents (LMAs) varies by atherosclerotic cardiovascular disease (ASCVD) risk. OBJECTIVE: To examine the relationship between LDL-C levels, adherence to LMAs, and ASCVD risk. METHODS: Adults (n = 4,262) prescribed LMAs between 2013 and 2023 (median age 60 years, 49% male) were categorised into low (<5%), borderline (5% to <7.5%), intermediate (7.5% to <20%), and high (≥20%) 10-year ASCVD risk groups. Adherence was defined as having ≥1 prescription of LMA every 6 months, with adherence trajectories identified over 5 years using group-based trajectory analysis: gradual decline, rapid decline, and early discontinuation. RESULTS: Average LDL-C decreased from 3.6 ± 1.1 mmol/L (139.2 ± 42.5 mg/dL) to 2.7 ± 1.1 mmol/L (104.4 ± 42.5 mg/dL) across all risk groups, with only 23% achieving <1.8 mmol/L (69.6 mg/dL) and 18% achieving ≥50% reduction. LDL-C was highest in the early discontinuation trajectory, across all ASCVD risk groups, averaging 2.9 mmol/L (112.1 mg/dL) in the low ASCVD risk group (42%), 2.8 mmol/L (108.3 mg/dL) in the borderline (13%), 2.5 mmol/L (96.7 mg/dL) in the intermediate (33%), and 2.3 mmol/L (88.9 mg/dL) in the high-risk group (11%). Higher LDL-C was associated with younger age, being male, non-smoking status, absence of diabetes, untreated blood pressure, early LMA discontinuation, higher total cholesterol ratio, and lower high-density lipoprotein cholesterol. CONCLUSION: Long-term adherence to LMAs remains a challenge, particularly in low-risk. Target achievement was poor, highlighting gaps in therapeutic optimization, patient engagement, and monitoring.