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. 2025 Mar 4;11(3):212-218.
doi: 10.4103/bc.bc_81_24. eCollection 2025 Jul-Sep.

External validation of N2H3 nomogram to predict outcomes in patients with acute ischemic stroke treated by intravenous thrombolysis

Huai-Mei Zhang  1 , Zi-Duo Shen  1 , Yang Qu  1 , Peng Zhang  1 , Reziya Abuduxukuer  1 , Li-Juan Wang  2 , Yu Li  3 , Yu-Mei Chen  4 , An-Ran Liu  5 , Xiao-Dong Liu  6 , Li-Li Zhao  7 , Chun-Yu Yang  8 , Jing Yao  9 , An-Ying Wang  10 , Yong-Fei Jiang  11   12 , Jin-Cheng Wang  7 , Chen-Peng Dong  13 , Fang-Fang Liu  14 , Li Li  15 , Ying-Bin Qi  15 , Chun-Fei Wang  16 , Hao Li  13 , Li-Ying Zhang  13 , Wen-Juan Ma  17 , Zhen-Ni Guo  1   18 , Yi Yang  1
Affiliations

External validation of N2H3 nomogram to predict outcomes in patients with acute ischemic stroke treated by intravenous thrombolysis

Huai-Mei Zhang et al. Brain Circ. .

Abstract

Background: The N2H3 model was evaluated for forecasting the 3-month outcomes for patients experiencing acute ischemic stroke who received intravenous thrombolysis (IVT), in our previous study. The present study aimed to validate the predictive ability of the N2H3 model and to compare its accuracy to the THRIVE-c and START models (both of which are widely employed for prognostic predictions following IVT).

Methods: Our study prospectively enrolled consecutive stroke patients who received IVT from 16 hospitals. Cases from one hospital were included in External Validation Dataset 1, whereas External Validation Dataset 2 included patients from the other 15 hospitals. The effectiveness of each model in distinguishing outcomes was assessed by calculating the area under the receiver operating characteristic curve (AUC-ROC). In addition, the overall performance of the N2H3 model was assessed through the scaled Brier score.

Results: Finally, 794 patients were included, of which 582 were included in External Validation Dataset 1 and 212 in External Validation Dataset 2. The N2H3 model's AUC-ROC for forecasting unfavorable outcomes at 3-months was 0.810 (95% confidence interval [CI]: 0.771-0.848) in the first dataset and 0.782 (95% CI: 0.699-0.863) in the second dataset. For the START model, the AUC-ROCs in the two validation datasets were 0.729 (95% CI: 0.685-0.772) and 0.731 (95% CI: 0.649-0.772), respectively. The THRIVE-c model showed AUC-ROCs of 0.726 (95% CI: 0.682-0.770) and 0.666 (95% CI: 0.573-0.759), respectively. The Brier scores of the N2H3 model were 0.153 and 0.147 in cohorts 1 and 2, respectively.

Conclusions: The N2H3 model exhibited good predictive ability in both external validation cohorts. Moreover, it demonstrated advantages over the THRIVE-c and is not inferior to the START nomogram in this regard.

Trial registration: Clinical Research of Intravenous Thrombolysis for Ischemic Stroke in Northeast of China (CRISTINA) (identifier: NCT05028868).

Keywords: Acute ischemic stroke; intravenous thrombolysis; nomogram; prognosis.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
N2H3 model in the External Validation Dataset 1: receiver operating characteristic curve area = 0.810. ROC: Receiver operating characteristic curve
Figure 2
Figure 2
N2H3 model in the External Validation Dataset 2: receiver operating characteristic curve area = 0.782. ROC: Receiver operating characteristic curve
Figure 3
Figure 3
N2H3 model receiver operating characteristic curve (ROC) area = 0.810; START model ROC area = 0.729; THRIVE-c model ROC area = 0.726. ROC: Receiver operating characteristic curve
Figure 4
Figure 4
N2H3 model receiver operating characteristic curve (ROC) area = 0.782; START model ROC area = 0.731; THRIVE-c model ROC area = 0.666. ROC: Receiver operating characteristic curve
See this image and copyright information in PMC

References

    1. GBD 2021 Diseases and Injuries Collaborators. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: A systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403:2133–61. - PMC - PubMed
    1. Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, et al. Association of outcome with early stroke treatment: Pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004;363:768–74. - PubMed
    1. Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359:1317–29. - PubMed
    1. IST-3 collaborative group. Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): A randomised controlled trial. Lancet. 2012;379:2352–63. - PMC - PubMed
    1. Tsivgoulis G, Katsanos AH, Sandset EC, Turc G, Nguyen TN, Bivard A, et al. Thrombolysis for acute ischaemic stroke: Current status and future perspectives. Lancet Neurol. 2023;22:418–29. - PubMed

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