Intravenous Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke: Factors Affecting Clinical Outcomes
Abstract
Stroke is one of the leading causes of disability and death worldwide. Thrombolytic therapy using intravenous recombinant tissue plasminogen activator (rt-PA) is the recommended treatment. However, functional outcomes vary due to various factors. Objective: The aim of this study was to analyze the factors affecting clinical outcomes of acute ischemic stroke patients treated with intravenous rt-PA. Method: This research was a retrospective study with a total sample of 52 acute ischemic stroke patients who received intravenous rt-PA therapy. The research variable data were collected from medical records, then statistically analyzed and correlated with patient clinical outcomes. Data from medical records were collected based on inclusion and exclusion criteria, then statistically analyzed using STATA 13. Univariate analysis is presented in a list of categories according to the research variables determined by percentage (standard error). Bivariate analysis was tested using simple logistic regression and multivariate analysis using multiple logistic regression. Results: The results of this study showed that patient clinical outcomes are not significantly impacted by risk factors (age, gender, prior stroke history, comorbidities), COVID-19 vaccination, onset and severity of stroke, HCTS onset, dosage, or onset therapy. The side effects of intravenous rt-PA have a significant impact on patient clinical outcomes, including therapy response and discharge condition (p = 0.008, p < 0.05, and p = 0.012, OR 34.073 (95% CI 2.165 – 536.147)), but do not affect the length of hospital stay. Conclusions: In considering the other factors, the study indicates that patients experiencing adverse effects from intravenous rt-PA have worse clinical outcomes.
References
Acheampong P, Ford GA. (2012). Pharmacokinetics of Alteplase in The Treatment of Ischaemic Stroke. Expert Opin Drug Metab Toxicol. 8(2):271-281.
Alawneh KZ, Qawasmeh MA, Raffee LA, Al-Mistarehi AH (2022). Ischemic stroke demographics, clinical features and scales and their correlations: an exploratory study from Jordan. Future Sci OA, 2022 Aug;8(7):FSO809. Available from: http://dx.doi.org/10.2144/fsoa-2022-0017.
Alnaami I, Alhazzani A, Alburaidi I, Alkhayri M, Dibssan H, Alqahtani MS, et al. (2021). Demographic characteristics and types of stroke in Southwestern Saudi Arabia, and the potential demand of neuro endovascular specialists. Neurosciences (Riyadh), 2021 Jan; 26(1):62–8. Available from: http://dx.doi.org/10.17712/nsj.2021.1.20200104.
Badan Penelitian dan Pengembangan Kesehatan (BPPK) (2019). Laporan Nasional RISKESDAS 2018. Jakarta: Lembaga Penerbit Badan Penelitian dan Pengembangan Kesehatan (LPB) Kementerian Kesehatan Republik Indonesia. [cited 2025 May 07]. Available from: https://repository.badankebijakan.kemkes.go.id/id/eprint/3514/1/Laporan%20Riskesdas%202018%20Nasional.pdf.
Balami JS, Sutherland BA, Buchan AM. (2013). Complications associated with recombinant tissue plasminogen activator therapy for acute ischaemic stroke. CNS Neurol Disord Drug Targets. 2013 Mar;12(2):155-69. doi: 10.2174/18715273112119990050. PMID: 23394532.
Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. (2019). Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation, Mar 5;139(10):e56–528. Available from: http://dx.doi.org/10.1161/CIR.0000000000000659.
Cooray C, Karlinski M, Kobayashi A, Ringleb P, Kõrv J, Macleod MJ, et al. (2021). Safety and early outcomes after intravenous thrombolysis in acute ischemic stroke patients with prestroke disability. Int J Stroke, 2021 Aug;16(6):710–8. Available from: http://dx.doi.org/10.1177/1747493020954605.
Derraz I, Moulin S, Gory B, Kyheng M, Arquizan C, Costalat V, et al. (2023). Endovascular thrombectomy outcomes with and without intravenous thrombolysis for large ischemic cores identified with CT or MRI. Radiology, 2023 Oct;309(1):e230440. Available from: http://dx.doi.org/10.1148/radiol.230440.
Diedler J, Ahmed N, Sykora M, Uyttenboogaart M, Overgaard K, Luijckx GJ, et al. (2010). Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset. Stroke, 2010 Feb;41(2):288–94. Available from: http://dx.doi.org/10.1161/STROKEAHA.109.559724.
Dmytriw AA, Dibas M, Schirmer CM, Settecase F, Heran MKS, Efendizade A, et al. (2021). Age and Acute Ischemic Stroke Outcome in North American Patients With COVID-19. J Am Heart Assoc, 2021 Jul 20; 10(14):e021046. Available from: http://dx.doi.org/10.1161/JAHA.121.021046.
Dong MX, Hu QC, Shen P, Pan JX, Wei YD, Liu YY, Ren YF, Liang ZH, Wang HY, Zhao LB, Xie P. (2016). Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis. PLoS One. 2016 Jul 7;11(7):e0158848. doi: 10.1371/journal.pone.0158848. PMID: 27387385; PMCID: PMC4936748.
Frey BM, Boutitie F, Cheng B, Cho TH, Ebinger M, Endres M, Fiebach JB, Fiehler J, Ford I, Galinovic I, Königsberg A, Puig J, Roy P, Wouters A, Magnus T, Thijs V, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Simonsen CZ, Gerloff C, Thomalla G; WAKE-UP investigators (2020). Safety and efficacy of intravenous thrombolysis in stroke patients on prior antiplatelet therapy in the WAKE-UP trial. Neurol Res Pract. 2020 Nov 20;2:40. doi: 10.1186/s42466-020-00087-9. PMID: 33324940; PMCID: PMC7678217.
Gebara OC, Mittleman MA, Sutherland P, et al. (1995). Association between increased estrogen status and increased fibrinolytic potential in the Framingham Offspring Study. Circulation. 91(7): 1952-1958.
Huang YH, Zhuo ST, Chen YF, Li MM, Lin YY, Yang ML, Chen ZJ, et al. (2013). Factors influencing clinical outcomes of acute ischemic stroke treated with intravenous recombinant tissue plasminogen activator. Chinese Medical Journal 126(24):p 4685-4690, December 20, 2013. DOI: 10.3760/cma.j.issn.0366-6999.20132354.
Jauch EC, Cucchiara B, Adeoye O, Meurer W, Brice J, Chan YF, Gentile N, and Hazinski MF. (2010). 2010 American heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation, Volume 122, Issue 18_suppl_3, 2 November 2010; Pages S818-S828. https://doi.org/10.1161/CIRCULATIONAHA.110.971044.
Kain K, Catto AJ, Carter AM, et al. (2001). Decreased fibrinolytic potential in South Asian women with ischaemic cerebrovascular disease. Br J Haematol. 2001; 114(1): 155-161.
Katta A., Jillella T. (2025). Tissue Plasminogen Activator in Stroke: A Review on Medical Management of Stroke and Mechanism of Action of TPA, Contraindications, Time Sensitivity, Journal of Clinical Cardiology and Cardiology Research, BioRes Scientia Publishers. 4(1):1-6. DOI: 10.59657/2837-4673.brs.25.042.
Khedr EM, Abo-Elfetoh N, Hasan AM, et al. (2024). The impact of sex differences on stroke risk factors and 3-month outcomes in patients receiving thrombolytic therapy for acute ischemic stroke. Egypt J Neurol Psychiatry Neurosurg 60:126. https://doi.org/10.1186/s41983-024-00900-1.
Liao S, Chen W, Kuo J, Chen C. (2001). Association of serum estrogen level and ischemic neuroprotection in female rats. Neurosci Lett. 297(3): 159-162.
Liu C, Xie J, Sun S, Li H, Li T, et al. (2022). Hemorrhagic Transformation After Tissue Plasminogen Activator Treatment in Acute Ischemic Stroke. Cell Mol Neurobiol. 42(3):621-646.
Luo S, Zhuang M, Zeng W, Tao J (2016). Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Receiving Antiplatelet Therapy: A Systematic Review and Meta-analysis of 19 Studies. J Am Heart Assoc. 2016 May 20;5(5):e003242. doi: 10.1161/JAHA.116.003242. PMID: 27207999; PMCID: PMC4889195.
Maharani T, Juli C, Hermawan A (2021). Karakteristik luaran klinis neurologis pasien stroke iskemik berdasarkan NIHSS. J Kedokt Syiah Kuala, 2021 Dec 23;21(3). Available from: https://jurnal.usk.ac.id/JKS/article/view/20646.
Marja FA (2024). Gambaran karakteristik pasien penyakit stroke di ruang rawat inap rumah sakit umum daerah cut meutia aceh utara tahun 2021 dan 2022. Aceh: Fakultas Kedokteran Universitas Malikussaleh Lhokseumawe. Available from: https://rama.unimal.ac.id/id/eprint/714/5/Full-Text.pdf.
Mavridis A, Reinholdsson M, Sunnerhagen KS, Abzhandadze T. (2024). Predictors of functional outcome after stroke: Sex differences in older individuals. J Am Geriatr Soc. 2024; 72(7): 2100-2110. doi:10.1111/jgs.18963.
Mongkau L, Langi FLFG, Kalesaran AFC (2022). Studi ekologi prevalensi diabetes melitus dengan stroke di Indonesia. Prepotif: Jurnal Kesehatan Masyarakat, 2022 Jun 25; 6(2):1156–62. Available from: http://journal.universitaspahlawan.ac.id/index.php/prepotif/article/view/4027
National Institute of Neurological Disorders (NIND) and Stroke rt-PA Stroke Study Group - Massachusetts Medical Society. (1995). Tissue plasminogen activator for acute ischemic stroke. N Engl J Med, 333(24):1581–7. Available from: http://dx.doi.org/10.1056/NEJM199512143332401.
Phipps MS, Cronin CA (2020). Management of acute ischemic stroke. BMJ, 2020 Feb 13;368:l6983. Available from: http://dx.doi.org/10.1136/bmj.l6983.
Poorthuis MHF, Algra AM, Algra A, Kappelle LJ, Klijn CJM (2017). Female- and male-specific risk factors for stroke: A systematic review and meta-analysis. JAMA Neurol, 2017 Jan 1;74(1):75–81. Available from: http://dx.doi.org/10.1001/jamaneurol.2016.3482.
Qin H, Wang P, Zhang R, Yu M, Zhang G, Liu G, Wang Y. (2020). Stroke history is an independent risk factor for poor prognosis in ischemic stroke patients: Results from a large nationwide stroke registry. Curr Neurovasc Res. 2020;17(4):487-494. doi: 10.2174/1567202617666200817141837. PMID: 32807054; PMCID: PMC8493791. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8493791/.
Wang X, Carcel C, Wang R, et al. (2020). Worse prognosis in women, compared with men, after thrombolysis: An individual patient data pooling study of Asian acute stroke registries. International Journal of Stroke. 2020;16(7):784-791. doi:10.1177/1747493020938307.
Wang X, Tsuji K, Lee SR, Ning M, Furie KL, et al. (2004). Mechanisms of Hemorrhagic Transformation After Tissue Plasminogen Activator Reperfusion Therapy for Ischemic Stroke. Stroke. 35(11 Suppl 1):2726-2730.
Warach SJ, Dula AN, Milling TJ Jr. (2020). Tenecteplase Thrombolysis for Acute Ischemic Stroke. Stroke. 51(11):3440-3451.
World Health Organization (2019). Health data overview for the Republic of Indonesia [Internet]. [cited 2024 Jul 22]. Available from: https://data.who.int/countries/360.
Xu M, Guo J, Tao X, Zeng K (2021). The Efficacy and safety of intravenous thrombolysis in older chinese patients with acute ischemic stroke. Neurol India, 2021 Jan-Feb;69(1):91–6. Available from: http://dx.doi.org/10.4103/0028-3886.310086.
Yang SH, Shi J, Day AL, Simpkins JW. (2000). Estradiol exerts neuroprotective effects when administered after ischemic insult. Stroke 31(3): 745-750; discussion 9–50, 750.
Yu Y, Zhang FL, Qu YM, Zhang P, Zhou HW, Luo Y, et al. (2021). Intracranial calcification is predictive for hemorrhagic transformation and prognosis after intravenous thrombolysis in non-cardioembolic stroke patients. J Atheroscler Thromb, 2021 Apr 1;28(4):356–64. Available from: http://dx.doi.org/10.5551/jat.55889.
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