Abstract
BACKGROUND AND OBJECTIVES: In stroke patients directly admitted to thrombectomy-capable centers, the value of intravenous thrombolysis (IVT) with alteplase before thrombectomy is time dependent. While early IVT may improve outcomes, delayed IVT administration lowers the likelihood of benefit. To date, no previous cost-effectiveness study has considered onset-to-treatment time. This study evaluated the cost-effectiveness of intravenous (IV) alteplase plus thrombectomy vs thrombectomy alone in patients admitted directly to thrombectomy-capable centers across 16 countries, stratified by onset-to-IVT time. METHODS: A decision tree integrated with a Markov model estimated costs, quality-adjusted life years (QALYs), and incremental net monetary benefit (INMB) over 15 years. A willingness-to-pay threshold of one gross domestic product per capita was applied for each country. Effectiveness data were derived from individual patient data from 6 trials including patients with anterior circulation large-vessel occlusion eligible for both IVT and thrombectomy who presented directly to thrombectomy-capable centers. Costs were obtained from a literature review. Onset-to-IVT time was categorized as <140, 140-169, 170-199, and ≥200 minutes. One-way sensitivity and probabilistic sensitivity analyses were performed to check robustness of results. RESULTS: Ninety-day functional outcome distributions from 2,268 patients (median age 71 years; 44% female) were used to model cost-effectiveness in a hypothetical cohort of 10,000 patients. Without accounting for onset-to-IVT time, IV alteplase plus thrombectomy seemed cost-effective in 13 countries (INMB: $85-$3,618; 50-65% probability of cost-effectiveness) and not cost-effective in the United States, China, and Vietnam, with modest health gains (0.06-0.08 QALYs per patient). Time-stratified analyses revealed that IVT plus thrombectomy was cost-effective in 16 countries when onset-to-IVT time was <140 minutes (INMB: $615-$30,645; 82%-98% probability) and at 140-169 minutes (INMB: $86-$16,918; 51%-77% probability). However, IV alteplase plus thrombectomy was no longer cost-effective in 8 countries at 170-199 minutes. Universally, the INMB was negative for onset-to-IVT times exceeding 200 minutes. DISCUSSION: Cost-effectiveness of IV alteplase plus thrombectomy varies per country and onset-to-IVT time. IV alteplase plus thrombectomy is cost-effective when IVT can be administered within 170 minutes from symptom onset. Cost-effectiveness of IV alteplase plus thrombectomy diminishes progressively with longer onset-to-IVT times and becomes detrimental after 200 minutes.