Event-Driven Intensification and Persistent Therapeutic Inertia in LDL-C Management Among 1,033,703 Patients With...

Long-term control of low-density lipoprotein cholesterol (LDL-C) is key to reducing the risk of atherosclerotic cardiovascular disease (ASCVD), yet most large-scale evaluations have been cross-sectional.

This study aimed to characterize the long-term trends in LDL-C among patients with ASCVD and to identify factors associated with reaching LDL-C goals.

Using data from the cvMOBIUS-2 (Cardiovascular Multicenter Observational Investigation of Lipid Care in the United States-2) registry, which pools electronic health record data from 17 U.S. health systems, we identified adults with ASCVD and a baseline LDL-C ≥70 mg/dL. We used generalized estimating equations to model LDL-C trends and multivariable logistic regression to identify clinical factors associated with: 1) achieving an LDL-C <70 mg/dL at 12 months; and 2) therapeutic intensification, defined as statin initiation/increase or nonstatin addition, within 1 year.

Among 1,033,703 patients (median age 67.9 years; 49.2% women) with a median follow-up of 2.2 years (IQR: 1.1-3.8 years), LDL-C demonstrated a "drop-and-plateau" pattern: following an initial decline, mean LDL-C stalled well above 80 mg/dL and remained elevated throughout the remaining follow-up. A recurrent ASCVD event was strongly associated with both achieving LDL-C <70 mg/dL (OR: 2.18; 95% CI: 1.98-2.40) and therapeutic intensification (OR: 2.77; 95% CI: 2.34-3.27). Conversely, peripheral artery disease was associated with lower odds of goal attainment (OR: 0.70; 95% CI: 0.68-0.72) and intensification (OR: 0.73; 95% CI: 0.70-0.75).

In ASCVD patients, LDL-C levels plateau well above guideline targets following an initial decline. Because lipid management remains predominantly event-driven, proactive, system-level monitoring and timely intervention are urgently needed to reduce cumulative above-goal LDL-C exposure.