{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:49:20Z","timestamp":1791510560667,"version":"4.3.4"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi260325-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Given the high costs of treatment with proprotein convertase subtilisin\/kexin type 9 inhibitors (PCSK9i) and the limited US Food and Drug Administration label for these treatments in patients with stroke due to atherosclerotic disease, it is unknown whether these agents are cost-effective for reducing recurrent stroke events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260325-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To estimate the theoretical cost-effectiveness of currently available PCSK9i for the prevention of recurrent stroke in patients with high-risk intracranial arterial stenosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260325-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This economic evaluation was a post hoc trial-based cost-effectiveness analysis of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial from a health care sector perspective. Adult patients with stroke due to intracranial arterial stenosis were included in SAMMPRIS and randomized to aggressive medical management with or without intracranial arterial stenting. Patients from the SAMMPRIS trial with complete covariate data were included in this secondary analysis. Data were analyzed from January to December 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260325-7\">\n                    <jats:title>Exposure<\/jats:title>\n                    <jats:p>A base-case assumption of 32% relative risk reduction for stroke among PCSK9i based on its low-density lipoprotein\u2013lowering effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260325-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Based on trial-estimated transition probabilities, annual direct-to-consumer prices for 3 PCSK9i (alirocumab: $6600; evolocumab: $7200; and inclisiran: $7920) and estimated US-based stroke care costs in 2025 US dollars, a decision-analytic Markov cohort model was developed to estimate the cost-effectiveness of PCSK9i for reducing recurrent stroke over a 5-year time horizon, with a 7% annual drug discontinuation rate and a 3% discount rate for future costs and quality-adjusted life-year (QALYs). From 1000 Monte Carlo simulations, the probability of cost-effectiveness of 3 PCSK9i was estimated at a $120\u202f000\/QALY threshold. Sensitivity analyses evaluated at an alternative threshold ($50\u202f000\/QALY), treatment efficacy (20% to 50%), and stroke care costs (50% to 150% of base estimates). A patient perspective analysis reflecting patients\u2019 out-of-pocket costs with insurance coverage was also conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260325-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 367 patients from the SAMMPRIS included in this study, 88 were Black (24.0%), 260 were White (70.8%), and 19 Asian, Native Hawaiian or Pacific Islander, more than 1 race, or other (5.2%), and the median (IQR) age at enrollment was 59 (52-69) years. At current direct-to-consumer prices, the probability of cost-effectiveness at a willingness-to-pay threshold of $120\u202f000\/QALY over a 5-year horizon was 58.6% (95% CI, 55.5%-61.6%) for alirocumab, 53.8% (95% CI, 50.7%-56.9%) for evolocumab, and 36.7% (95% CI, 33.8%-39.7%) for inclisiran.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260325-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>This theoretical framework suggests that alirocumab and evolocumab were cost-effective for preventing recurrent stroke in patients with severe intracranial atherosclerosis, with all agents cost-effective under current cost-sharing programs offered by commercial and Medicare plans.<\/jats:p>\n                  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