Presentation (CTI)

OBJECTIVES: In Denmark, patients at risk for or diagnosed with atherosclerotic cardiovascular disease (ASCVD) are primarily treated with statins due to strict PCSK9i eligibility criteria and limited use of other lipid-lowering therapies, leaving many patients above LDL-C goals. This research evaluates the health impact of adding oral PCSK9i treatment, enlicitide, to maximally tolerated statins in patients not achieving LDL-C goals.
METHODS: A Markov model informed by phase 3 enlicitide trials (CORALreef Lipids, HeFH, and AddOn) was adapted to reflect Danish clinical practice. Patients at high or very high risk of ASCVD and patients diagnosed with ASCVD not reaching LDL-C goals (<2.6 mmol/L, <1.8 mmol/L, and <1.4 mmol/L, respectively) were modeled to receive enlicitide on top of statins or statins alone over a lifetime horizon. Outcomes included ischemic stroke (IS), myocardial infarction (MI), urgent arterial revascularization for unstable angina (UR), elective arterial revascularization (ER), acute limb ischemia (ALI), and cardiovascular death (CV death). Transition probabilities were based on real-world ASCVD data from the Clinical Practice Research Datalink. The LDL-C efficacy data for enlicitide was estimated through an indirect treatment comparison. Event-risk reductions were based on Cholesterol Treatment Trialists data.
RESULTS: Compared with statins alone, treatment intensification with enlicitide plus statins was estimated to prevent 3.9 CV deaths and 8.7 non-fatal cardiovascular events per 100 patients treated, including 2.3 IS, 3.4 MI, 1.2 UR, 1.0 ER, and 0.8 ALI. Among patients at risk of ASCVD, treatment intensification was estimated to prevent 4.3 CV death and 8.5 non-fatal CV events per 100 patients treated. Corresponding estimates were 2.9 CV deaths and 8.9 non-fatal ASCVD events per 100 patients treated among patients diagnosed with ASCVD.
CONCLUSIONS: For patients at risk for or diagnosed with ASCVD not achieving LDL-C goals, intensification of lipid-lowering therapy with enlicitide plus statins may substantially reduce cardiovascular morbidity and mortality.