Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr 28:14:1118711.
doi: 10.3389/fneur.2023.1118711. eCollection 2023.

Predictive model of recurrent ischemic stroke: model development from real-world data

Marwa Elsaeed Elhefnawy  1 , Siti Maisharah Sheikh Ghadzi  1 , Orwa Albitar  1 , Balamurugan Tangiisuran  1 , Hadzliana Zainal  1 , Irene Looi  2 , Norsima Nazifah Sidek  3 , Zariah Abdul Aziz  3 , Sabariah Noor Harun  1
Affiliations

Predictive model of recurrent ischemic stroke: model development from real-world data

Marwa Elsaeed Elhefnawy et al. Front Neurol. .

Abstract

Background: There are established correlations between risk factors and ischemic stroke (IS) recurrence; however, does the hazard of recurrent IS change over time? What is the predicted baseline hazard of recurrent IS if there is no influence of variable predictors? This study aimed to quantify the hazard of recurrent IS when the variable predictors were set to zero and quantify the secondary prevention influence on the hazard of recurrent ischemic stroke.

Methods: In the population cohort involved in this study, data were extracted from 7,697 patients with a history of first IS attack registered with the National Neurology Registry of Malaysia from 2009 to 2016. A time-to-recurrent IS model was developed using NONMEM version 7.5. Three baseline hazard models were fitted into the data. The best model was selected using maximum likelihood estimation, clinical plausibility, and visual predictive checks.

Results: Within the maximum 7.37 years of follow-up, 333 (4.32%) patients had at least one incident of recurrent IS. The data were well described by the Gompertz hazard model. Within the first 6 months after the index IS, the hazard of recurrent IS was predicted to be 0.238, and 6 months after the index attack, it reduced to 0.001. The presence of typical risk factors such as hyperlipidemia [HR, 2.22 (95%CI: 1.81-2.72)], hypertension [HR, 2.03 (95%CI: 1.52-2.71)], and ischemic heart disease [HR, 2.10 (95%CI: 1.64-2.69)] accelerated the hazard of recurrent IS, but receiving antiplatelets (APLTs) upon stroke decreased this hazard [HR, 0.59 (95%CI: 0.79-0.44)].

Conclusion: The hazard of recurrent IS magnitude differs during different time intervals based on the concomitant risk factors and secondary prevention.

Keywords: NONMEM; ischemic stroke; pharmacometrics; recurrent; time to event model.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Baseline hazard during different time intervals after index IS; during first 6 months after index IS, after 6 months.
Figure 2
Figure 2
Effect of covariates on hazard of recurrent IS after index IS.
Figure 3
Figure 3
Kaplan-Meier plots showing the IS survivor function (probability of not having recurrent ischemic stroke) throughout different time intervals. The final time-to-event model of the internal data.
Figure 4
Figure 4
Survival (probability of not having recurrent IS after index IS) among (i) patients did not receive APLT vs. (ii) patients received APLT.
See this image and copyright information in PMC

References

    1. Zheng S, Yao B. Impact of risk factors for recurrence after the first ischemic stroke in adults: a systematic review and meta-analysis. J Clin Neurosci. (2019) 60:24–30. 10.1016/j.jocn.2018.10.026 - DOI - PubMed
    1. Oza R, Rundell K, Garcellano M. Recurrent ischemic stroke: strategies for prevention. Am Fam Phys. (2017) 96:436–40. - PubMed
    1. Putaala J, Liebkind R, Gordin D, Thorn LM, Haapaniemi E, Forsblom C, et al. . Diabetes mellitus and ischemic stroke in the young: clinical features and long-term prognosis. Neurology. (2011) 76:1831–7. 10.1212/WNL.0b013e31821cccc2 - DOI - PubMed
    1. Jin P, Diaz IM, Stein L, Thaler A, Tuhrim S, Dhamoon MS. Intermediate risk of cardiac events and recurrent stroke after stroke admission in young adults. Int J Stroke. (2018) 13:576–84. 10.1177/1747493017733929 - DOI - PubMed
    1. Varona JF. Long-term prognosis of ischemic stroke in young adults. Stroke Res Treatment. (2011) 2011:1559. 10.4061/2011/879817 - DOI - PMC - PubMed

LinkOut - more resources