The journey to LDL-C goal in the era of combination lipid lowering therapy and why it matters for ASCVD patients: a UK perspective

Objective: We aim to explore the concept of distance and journey to goal, and consideration of these 2 elements a priori when choosing LLT.

Methods: Modelling of expected % LDL-C reductions was carried out on a range of hypothetical patients' baseline LDL-C values prior to any LLT being commenced. Therapies were then added in a stepwise manner based on the pathway demonstrated in current national guidance and compared with goal achievement on a novel LLT optimization pathway implemented in Morecambe Bay NHS Trust.

Results: Modelling of a stepwise lipid management pathway shows that high-intensity statin monotherapy is not sufficient in most modelled baseline LDL-C scenarios to achieve guideline-recommended goals. Furthermore, ezetimibe second line may preclude 3^rd line injectable prescribing and lead to "ezetimibe limbo" where the patient is now below the reimbursement threshold for injectable prescribing but still not achieving their LDL-C target. Overall goal achievement is poor across the spectrum of modelled LDL-C levels. In contrast, by following the Morecambe Bay pathway all patients on statin for the range of hypothetical baseline LDL-C levels can reach an LDL-C target of < 1.8 mmol/L.

Conclusions: This study identifies a therapeutic gap when following a stepwise approach highlighted by recent national guidance. Our proposal of a novel pathway highlights that the order in which drugs are added is important in the context of national reimbursement thresholds and allows LDL-C goal to be reached in a timely manner, regardless of the starting baseline LDL-C level.