Abstract
<jats:p>Importance Evolocumab reduces major adverse cardiovascular events (MACE) in patients with clinically evident atherosclerotic cardiovascular disease (ASCVD) and in patients at high cardiovascular (CV) risk but without a prior myocardial infarction (MI) or stroke. While evolocumab is shown to be cost–effective in clinically evident ASCVD, emerging CV outcomes evidence and newer guideline recommendations warrant assessment in patients at high CV risk without a prior MI or stroke. Objective To evaluate the cost–effectiveness of evolocumab added to standard therapy compared with standard therapy alone in patients at high CV risk without a prior MI or stroke, as represented by the VESALIUS–CV trial. Design, Setting, and Participants A previously published Markov cohort state–transition model was adapted to simulate VESALIUS–CV patients over a lifetime horizon. Health states included high–risk without a prior MI or ischemic stroke (IS), non–fatal MI, non–fatal IS, post–MI, post–IS, CV death, and non–CV death. Revascularization (RV) was modeled as a procedure with associated costs. The base case considered a US payer perspective and CV risk reduction inputs from evolocumab CV outcomes trials, including VESALIUS–CV, FOURIER, and FOURIER–OLE. Three scenario analyses were evaluated. Scenario 1 retained the US payer perspective and applied CV risk reduction estimates based on the Cholesterol Treatment Trialists' (CTT) Collaboration 2010 meta–analysis. Scenarios 2 and 3 adopted a US societal perspective, using evolocumab CV outcomes trial-based and 2010 CTT Collaboration–based risk reduction estimates, respectively. Main Outcomes and Measures The model outcomes included MACE (defined as MI, IS, or CV death), RV procedures, total costs, life–years (LYs), quality–adjusted life–years (QALYs), and incremental cost–effectiveness ratio (ICER). Results In the base case, at the current direct–to–patient price of $3,107 per year, evolocumab added to standard therapy was associated with lifetime reductions of 0.24 MACE and 0.17 RV procedures per person, incremental costs of $24,430, incremental QALYs of 0.34, and an ICER of $71,162 per QALY gained. Evolocumab remained cost–effective across all evaluated scenarios, with ICERs of $42,094, $51,160, and $20,152 per QALY in Scenarios 1, 2, and 3, respectively. Conclusions and Relevance In patients at high CV risk without a prior MI or stroke, evolocumab added to standard therapy was projected to improve CV outcomes and quality–adjusted survival. At the current direct–to–patient price of $3,107 per year, evolocumab was cost–effective in the base–case analysis, with an ICER of $71,162 per QALY gained, and remained cost–effective across scenario analyses, with ICERs ranging from $20,152 to $51,160 per QALY. These estimates were substantially below the $120,000 per QALY threshold defined in the 2025 American Heart Association/American College of Cardiology cost/value methodology statement.</jats:p>