Nguyen CP, Lahr MMH, van der Zee DJ, Rinkel LA, van Voorst H, Pinckaers FME, Cavalcante F, LeCouffe NE, Kappelhof M, Treurniet KM, et al, on behalf of the CONTRAST Consortium. Endovascular Thrombectomy Alone for Large Vessel Occlusion: A Cost-Effectiveness Evaluation Based on Meta-Analyses. Stroke. 2024;55:2482-2491.

The management of acute ischemic stroke due to large vessel occlusion (LVO) has evolved significantly in recent years. While the combination of intravenous thrombolysis (IVT) with alteplase and endovascular thrombectomy (EVT) remains the standard of care, questions have arisen about the added benefit of IVT in patients who can receive prompt EVT. This debate stems from concerns about potential delays to EVT and increased risk of intracranial hemorrhage with IVT. To address this question, six randomized controlled trials (RCTs) have compared EVT alone to IVT plus EVT in LVO patients. While two trials (DIRECT-MT and DEVT) suggested non-inferiority of EVT alone, the others (SKIP, MR CLEAN-NO IV, SWIFT-DIRECT, and DIRECT-SAFE) could not definitively rule out potential benefits of IVT before EVT. Given this equipoise, cost-effectiveness becomes an important consideration in clinical decision-making.

Nguyen and colleagues recently conducted a cost-effectiveness analysis comparing EVT alone to IVT plus EVT for LVO patients presenting directly to EVT-capable centers in the Netherlands. Their study utilized a Monte Carlo simulation with a 15-year time horizon, incorporating data from a hypothetical cohort of 10,000 patients treated within 4.5 hours of symptom onset.

The authors based their primary analysis on intention-to-treat data from the six aforementioned trials, using published modified Rankin Scale distributions from a patient-level meta-analysis. They found that IVT before EVT resulted in slightly higher costs ($2,817 extra per patient) but also a modest gain in quality-adjusted life years (0.05 QALYs per patient). This translated to an incremental cost-effectiveness ratio of $62,287 per QALY.

Probabilistic sensitivity analysis revealed considerable uncertainty in the results. At willingness-to-pay thresholds of $52,500 and $84,000 per QALY, IVT before EVT had probabilities of being cost-effective of 45% and 54%, respectively. The scatter plot of simulations (Figure 2) visually demonstrates this uncertainty, with results distributed across quadrants representing both higher and lower effectiveness for IVT plus EVT.

The authors also conducted a comprehensive analysis of the cost-effectiveness of endovascular thrombectomy (EVT) alone versus intravenous thrombolysis (IVT) with alteplase before EVT in patients with large vessel occlusion (LVO). Their approach included three additional scenarios to assess the robustness of their findings: (1) post hoc modified as-treated analysis from six RCTs; (2) intention-to-treat analysis from European RCTs (MR CLEAN-NO IV and SWIFT-DIRECT); and (3) intention-to-treat analysis from a Dutch RCT (MR CLEAN-NO IV). These scenarios yielded varying probabilities of cost-effectiveness for IVT with alteplase before EVT. At the $52,500 willingness-to-pay (WTP) threshold, the probabilities were 64%, 81%, and 50% for scenarios 1, 2, and 3, respectively. At the higher $84,000 WTP threshold, these probabilities increased to 79%, 91%, and 67%. A key finding of this study was the impact of variable functional outcomes, as measured by modified Rankin Scale (mRS) distributions, on cost-effectiveness results. This variability across different scenarios emphasizes the need for careful consideration of patient populations and treatment settings when interpreting and applying cost-effectiveness data.

The study had several limitations that warrant consideration: (1) The use of mRS distributions from published meta-analyses may have restricted certain subgroup analyses; (2) the short follow-up period in the MR CLEAN trial could have affected the accuracy of long-term transition probabilities; (3) the absence of cost data for adverse events, such as symptomatic intracranial hemorrhage management, may have impacted the overall cost estimates; (4) the analysis focused solely on alteplase, as tenecteplase is not currently used for LVO patients in the Netherlands.

Despite these limitations, the study results suggest potential cost-effectiveness, particularly at higher WTP thresholds, and provide valuable insights into the potential cost-effectiveness of IVT before EVT in the Dutch healthcare context. Future research directions should include evaluating the cost-effectiveness of tenecteplase before EVT compared to EVT alone, identifying specific subgroups of patients undergoing EVT who may derive greater economic benefit from prior IVT, and conducting longer-term follow-up studies to improve the accuracy of transition probabilities and cost estimates.