Abstract DP158: Cost-effectiveness of theoretical benefit of PCSK9 inhibitor use in patients with stroke due to severe intracranial atherosclerosis: A post hoc analysis of the SAMMPRIS trial

Introduction: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) can reduce low density lipoprotein (LDL) levels by approximately 60% when added to maximally tolerated statins, which leads to a decrease in atherosclerotic events. For patients with intracranial atherosclerosis >70%, who are at high risk of recurrent stroke, these agents may significantly lessen recurrent stroke events. Methods: With individual patient data from the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study, we utilized prior estimates of the LDL-lowering effect on reduction of recurrent stroke rates to estimate cost-effectiveness of PCSK9i. Using a base-case assumption of 32% relative risk reduction for recurrent stroke in this population, and cost parameters drawn from current US healthcare expenditures (with a willingness-to-pay [WTP] threshold of <$100,000/quality-adjusted life-year [QALY]), we generated 1,000 Monte Carlo simulations with parameter distributions calibrated to reflect real-world healthcare data variability. Sensitivity analyses were repeated for a WTP threshold of <$50,000/QALY, for lower and higher margins of efficacy for stroke reduction (20% and 50%, respectively), and lower and higher margins of recurrent stroke care costs (50% and 150% of base, respectively). Results: Of the 367 included patients, the median age was 59 years, with 63.8% male and 70.8% being White. At current out-of-pocket prices, the probability of cost-effectiveness of alirocumab, evolocumab, and inclisiran were 30.7%, 24.1%, and 19.2%, respectively, at a WTP threshold of <$100,000 over a 5-year horizon. PCSK9i would be >50% cost-effective at a margin of $5,000/year and a WTP threshold of <$100,000. With higher costs of recurrent stroke (150% of base), there is a 59.1% probability of cost-effectiveness for agents priced at $5,000/year; with higher treatment effectiveness (50%), the probability of cost-effectiveness increases to 74.3%. Conclusion: This theoretical framework does not demonstrate cost-effectiveness of currently available PCSK9i for the prevention of recurrent ischemic stroke in patients with severe intracranial atherosclerosis. The added benefits of PCSK9i in reducing coronary events and disability associated with lower rates of stroke or myocardial infarction may render these agents cost-effective for all atherosclerotic outcomes; however, this warrants further study.