Previous Article in Journal
Multi-Drug Resistant Gram-Negative Sepsis in Neonates: The Special Role of Ceftazidime/Avibactam and Ceftolozane/Tazobactam
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Medicines
Volume 12
Issue 3
10.3390/medicines12030018
medicines-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

First-Ever Stroke Outcomes in Patients with Atrial Fibrillation: A Retrospective Cross-Sectional Study

by
Ivanka Maduna
1,2,
Dorotea Vidaković
3,
Petra Črnac
4,
Christian Saleh
5 and
Hrvoje Budinčević
1,4,6,*
1
Faculty of Medicine Osijek, J.J. Strossmayer University of Osijek, 31000 Osijek, Croatia
2
Health Center of Osijek-Baranja County, 31000 Osijek, Croatia
3
Department of Neurology, National Memorial Hospital of Vukovar, 32000 Vukovar, Croatia
4
Department of Neurology, Sveti Duh University Hospital, 10000 Zagreb, Croatia
5
University of Basel, 4001 Basel, Switzerland
6
Department of Psychiatry and Neurology, Faculty of Dental Medicine and Health, J.J. Strossmayer University of Osijek, 31000 Osijek, Croatia
*
Author to whom correspondence should be addressed.
Medicines 2025, 12(3), 18; https://doi.org/10.3390/medicines12030018
Submission received: 9 February 2025 / Revised: 8 April 2025 / Accepted: 14 July 2025 / Published: 24 July 2025
(This article belongs to the Section Cardiology and Vascular Disease)
Browse Figures
Versions Notes

Abstract

Background/Objectives: Atrial fibrillation (AF) is the most significant modifying risk factor for the development of cardioembolic stroke, which is associated with worse outcomes and higher intrahospital mortality compared to other types of ischemic stroke. Antithrombotic medications are administered as prophylactic treatment in patients with a risk of stroke. The aim of this study was to determine outcome measures in patients with first-ever ischemic stroke and AF regarding prior antithrombotic therapy. Methods: We collected data on stroke risk factors, CHADS2 score, and international normalized ratio (INR) value in the context of warfarin therapy, as well as data related to localization, stroke severity, and functional outcome at discharge. Results: A total of 754 subjects with first-ever ischemic stroke and AF were included in this cross-sectional study (122 on warfarin, 210 on acetylsalicylic acid, and 422 without prior antithrombotic therapy). The diagnosis of AF was previously unknown in 31% of the subjects. Stroke risk factors (arterial hypertension, hyperlipidemia, diabetes mellitus, and cardiomyopathy) were significantly lower in the group without prior antithrombotic therapy. The anticoagulant group was significantly younger (p = 0.001). Overall, 45.4% of subjects with a previously known AF event and a high risk of developing stroke received anticoagulant therapy. Participants on warfarin had a significantly better functional outcome than those on antiplatelet therapy or without prior antithrombotic therapy (median mRS 4 vs. 5 vs. 5; p = 0.025) and lower NIHSS scores, although the difference was not statistically significant (median 10 vs. 12 vs. 12; p = 0.09). There was no difference between stroke localization among groups (p = 0.116). Conclusions: Our study showed that, in our cohort, first-ever ischemic stroke due to AF was more common in women. Subjects on prior anticoagulant therapy had more favorable outcomes at discharge.

1. Introduction

Atrial fibrillation (AF) is one of the most significant risk factors for ischemic stroke, particularly cardioembolic stroke, which is associated with higher mortality and greater disability compared to other stroke subtypes [1]. Tracz et al. showed that post-stroke patients with AF have a more severe prognosis with a higher mortality rate after ischemic stroke than patients with sinus rhythm, without an independent negative effect on the long-term outcome after stroke [2]. Clinically manifest AF has been shown to increase stroke risk three- to five-fold [3], making stroke prevention through antithrombotic therapy essential [4]. Stroke prevention in patients with AF relies on risk stratification using the CHADS2 and CHA2DS2-VASc scoring systems [5]. Anticoagulation is recommended for men with a CHA2DS2-VASc score of 2 points or higher and for women with a CHA2DS2-VASc score of 3 points or higher. Lower-risk patients require individualized evaluation. The prophylactic use of anticoagulant therapy in patients with AF without a prior stroke or transient ischemic attack (TIA) is based on individualized risk assessment. Additional risk factors not included in the CHA2DS2-VASc score may influence the decision. These include elevated biomarkers (NT-proBNP, troponins), echocardiographic findings, genetic predisposition to thrombosis, chronic inflammatory diseases, chronic kidney disease, and a tendency for prolonged episodes of atrial fibrillation [5,6,7,8]. A meta-analysis by Hart et al. has demonstrated the superior prophylactic efficacy of anticoagulant therapy compared to antiplatelet therapy [9]. Previous studies that included consecutive ischemic strokes in AF patients showed an association between prior anticoagulation and improved ischemic stroke outcomes [10,11,12]. Although Direct Oral Anticoagulants (DOACs) are generally preferred and recommended over warfarin due to their favorable pharmacokinetic properties, including predictable dosing, fewer dietary restrictions, and the reduced need for frequent monitoring, warfarin remains widely used, particularly in low- and middle-income countries [13,14,15]. Moreover, the optimal starting dose of warfarin remains unclear [16]. Non-pharmacological treatment options for patients who are unable to take anticoagulant therapy include surgical and endovascular occlusion of the left atrial appendage [17].
This study aimed to determine outcome measures in patients with first-ever ischemic stroke and AF regarding prior antithrombotic therapy.

2. Materials and Methods

This study was a retrospective cross-sectional study. Data were collected by analyzing the medical records of patients admitted to the Department of Neurology, Sveti Duh University Hospital, Zagreb, Croatia, with first-ever ischemic stroke and AF in the period from 1 January 2004 to 31 December 2013. The study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Criteria for excluding subjects from the study included being under 18 years of age, having a hemorrhagic stroke, a prosthetic heart valve, anticoagulant therapy other than warfarin, antiplatelet therapy other than acetylsalicylic acid, dual antithrombotic therapy, thrombolysis and/or mechanical thrombectomy, missing values, and inadequate data. Patients receiving DOACs were excluded, as the lower prevalence of DOAC use during the study period resulted in an insufficient sample size for meaningful statistical analysis. Data collected for each patient included age, gender, risk factors, cerebrovascular risk, stroke size, and localization. The international normalized ratio (INR) value was also included in subjects on anticoagulant therapy. The risk factors analyzed were arterial hypertension, hyperlipidemia, diabetes mellitus, and cardiomyopathy. Ischemic strokes were diagnosed based on clinical examination and neuroradiological processing, including brain computerized tomography (CT) or magnetic resonance imaging (MRI). The risk of stroke development was evaluated using the CHADS2 scoring system (congestive heart failure, hypertension, age > 75 years, diabetes mellitus, stroke/TIA/thromboembolism), with a score of 1 point assigned for each presented risk factor [5]. Stroke severity for each subject was assessed at hospital admission using the NIHSS, based on a neurological clinical examination. The Oxford Community Stroke Project (OCSP) classification was used to assess stroke localization based on the clinical presentation of neurological deficits [18]. The size of vital cerebral tissue damage was not estimated. The subject’s level of disability and functional dependency at discharge was evaluated by the modified Rankin Scale (mRS) [19].
This study obtained approval from the Ethics Committee of the Faculty of Medicine, Osijek, and the Ethics Committee of the Sveti Duh University Hospital.

Statistical Methods

Categorical data are represented by absolute and relative frequencies. Numerical data were described by the median and the limits of the interquartile range (IQR). Differences in categorical variables were tested with the χ2 test. Bonferroni’s χ2 adjusted residual analysis, a post hoc test, was used to test for cohort significance after obtaining a statistically significant χ2 test. The normality of the distribution of numerical variables was tested with the Shapiro–Wilk test. Differences in numerical variables among the three groups were analyzed using the Kruskal–Wallis test, followed by post hoc pairwise comparisons, and among two groups with Mann-Whitney U test Correlation was tested using Spearman’s rank correlation coefficient. All p values are two-sided. The significance level was set at Alpha = 0.05. The statistical analysis programs used were IBM SPSS Statistics for Windows (version 21.0, IBM Corp., Armonk, NY, USA).

3. Results

The study included 754 subjects with first-ever stroke and AF. Diagnosis of AF was previously known in 520 (69%) subjects, and 332 (44%) subjects were on prior antithrombotic therapy, of which 122 (36.7%) were taking anticoagulants, while 210 (63.3%) were taking antiplatelet therapy. Overall, the median of the NIHSS scale was 12 (IQR: 7–17), the median of the mRS scale was 5 (2–6), and the median of the CHADS2 grading system was 3 (IQR: 2–3).
Differences among risk factors of subjects regarding prior antithrombotic therapy are shown in Table 1. Kruskal–Wallis test and post hoc pairwise comparison of CHADS2 showed significant differences between the anticoagulant group and the antiplatelet group (p < 0.001, mean 3, IQR: 2–3, minimum 0–maximum 4 vs. mean 3, IQR: 2–3, minimum 1–maximum 4, respectively) and between the antiplatelet group and the group without antithrombotic therapy (p < 0.001, mean 3, IQR: 2–3, minimum 1–maximum 4 vs. mean 3, IQR: 2–3, minimum 0–maximum 4, respectively).
Among subjects with previously undiagnosed AF and without antithrombotic therapy, more than two-thirds had CHADS2 ≥ 2. (Table 2).
Although there was no significant difference in median NIHSS scores among the groups of subjects (the Kruskal–Wallis test, anticoagulant group vs. antiplatelet group vs. group without prior antithrombotic therapy; median 10 [IQR: 5–16] vs. 12 [IQR: 7–17] vs. 12 [IQR: 7–17]; p = 0.09), there is a trend toward lower NIHSS scores in the group of subjects on anticoagulant therapy (Figure 1). When compared to the anticoagulant group, there was a significant difference in the distribution of NIHSS scores among non-warfarin patients (antiplatelet group and group without antithrombotic therapy), with there being lower NIHSS scores in the anticoagulant group (Mann–Whitney U test; p = 0.03).
The Kruskal–Wallis test revealed a statistically significant difference in mRS scores among the groups (p = 0.005). The group of subjects on anticoagulant therapy had a median mRS score of 4 (IQR: 2–5), indicating a slightly lower disability level on average compared to the other groups. A pairwise comparison showed significant differences between the group on anticoagulant therapy and the group on antiplatelet therapy. The groups of subjects on antiplatelet therapy and those without antithrombotic therapy both had a median score of 5 and an IQR of 2–6, suggesting broader variability (Figure 2). Overlapping IQRs imply variability in mRS scores across all groups, suggesting the potential influence of additional factors on subject outcomes. There is a statistically significant but weak positive correlation between the CHADS2 score and the mRS score (r = 0.169, p < 0.001).
Although the median mRS in the anticoagulant group is 4 (IQR: 2–5), a chi-square test for independence indicated that the observed count of subjects on anticoagulant therapy with mRS scores between 2 and 3 is significantly higher than in other groups. (p = 0.025). This suggests that subjects receiving anticoagulant therapy more often have better outcomes than groups on antiplatelet therapy and without therapy (Table 3).

4. Discussion

This study analyzed 754 subjects with AF and first-ever stroke, of whom more than 60% were women. The findings indicate that women with AF have a 1.75-fold higher stroke incidence than men. While previous studies have reported up to a 4.6-fold increased risk of cardioembolic stroke in women [20,21,22], the underlying cause remains unclear. These results suggest that the elevated risk is likely driven by a higher prevalence of atrial fibrosis and the prothrombotic effects of female sex hormones rather than clot formation [23]. The results of this study are consistent with a meta-analysis in which it was shown that, in about 30% of cases, the diagnosis of AF was established only during the treatment of stroke [24]. Some of these strokes could have been prevented if the diagnosis had been known, which could have been achieved by more frequent heart rhythm monitoring in at-risk subjects [25]. Almost half of the subjects with AF and CHADS2 score of 2 or above were without anticoagulant therapy. A possible reason for the too infrequent use of anticoagulant therapy is the existence of contraindications that were not included in this study. Another possible reason is the fear of complications, mainly bleeding, in the elderly. Previous studies show that warfarin, compared to acetylsalicylic acid, significantly reduces the risk of developing a first-ever stroke in the elderly (over 75 years of age). Elderly people also have a higher risk of developing a stroke than the risk of bleeding. That is why the benefit of anticoagulant therapy is most significant in the elderly [3,26]. Despite this, in this study, as well as in earlier studies [27], subjects on warfarin were significantly younger than the subjects on antiplatelet therapy. However, most subjects in both groups were over 70 years old. Ischemic strokes associated with AF are more severe, have a worse outcome, and have a higher mortality rate than other stroke subtypes [28,29]. In this study, the median NIHSS score was 12 (IQR: 7–17), indicating that strokes in patients with AF are often severe. This may be explained by the predominantly cardioembolic origin of strokes in AF, where the sudden occlusion of large cerebral arteries frequently leads to extensive cortical infarcts, while lacunar infarcts are much rarer. Additionally, studies have demonstrated a significant reduction in cerebral blood flow in AF patients compared to those in sinus rhythm. This diminished perfusion contributes to larger infarct areas and more pronounced neurological deficits [29,30]. Consistent with this, previous studies have reported that ischemic strokes in AF patients are frequently classified as TACI or PACI according to the OCSP classification [30,31,32]. However, in this study, no significant difference was found in OCSP classification subcategories regarding prior therapy. The observed effect of acetylsalicylic acid in reducing the incidence of LACI and POCI is likely mediated by its role in modifying lipohyalinosis of cerebral blood vessels [33].
Previous studies show significantly more severe strokes in the antiplatelet group and those without prior antithrombotic therapy, compared to subjects on prior anticoagulant therapy [34,35]. Contrary to expectations, this study reveals that the difference in severity between subjects who received prior antithrombotic therapy and those without prior antithrombotic therapy is not statistically significant; however, it does show a tendency toward lower NIHSS scores. Moreover, patients in the anticoagulant group showed a lower distribution of NIHSS scores compared to those in the other groups. The difference from the current study may be due to inadequate warfarin titration with INR outside the target values. Also, a group without prior antithrombotic therapy had significantly fewer additional comorbidities (arterial hypertension, hyperlipidemia, diabetes mellitus, and cardiomyopathy). These factors might be expected to contribute to less severe strokes. However, despite the differences in comorbidity burden, the CHADS2 scores between the anticoagulant group and the group without prior antithrombotic therapy did not differ significantly. Additionally, data on therapy compliance was not observed in this study. Contrary to the study conducted by Jung et al. [27], where the difference in after-stroke disability between the anticoagulant group and the antiplatelet group was not significant, in this study, the anticoagulant group shows more favorable stroke outcomes (median mRS score: 4, IQR: 2–5 vs. 5, IQR: 2–6, respectively). A potential reason for this might be that, in the study by Jung et al., patients were not categorized based on whether they had a previous stroke [27]. It is shown that when recurrent stroke adds to the existing neurological deficit or hemorrhagic transformation, patients may be more prone to complications and a worse outcome [36,37].
According to data from previous studies, anticoagulant therapy significantly reduces functional dependence after a stroke [11,38]. Significantly lower median mRS scores were observed in the anticoagulant group compared to the antiplatelet group. Significantly higher observed frequencies of mRS scores 2 and 3 were noted in the anticoagulant group compared to both the antiplatelet group and the group without antithrombotic therapy, suggesting a trend toward better outcomes in the anticoagulant group and its superiority over antiplatelet therapy. The results of some studies show that antiplatelet therapy does not lead to a better outcome nor reduce the severity of stroke. Antiplatelet therapy significantly reduces the severity and outcome of strokes, but only in those caused by atherosclerosis of blood vessels [38,39,40]. Other studies show that prior use of antiplatelet therapy may still improve functional stroke outcome, but it is not better than prior anticoagulant therapy [12]. Since people with AF usually also have vascular diseases, the effect of antiplatelet therapy in improving the functional outcome is probably indirect and mediated by the impact on atherosclerotic vascular disease [41].
One limitation of this study is its cross-sectional design, which restricts the ability to infer causality. In this study, we also did not assess the severity of individual comorbidities, which could have varying effects on stroke severity. A comparison with neurological findings, which include the size of the stroke, was not conducted either. Due to the retrospective cross-sectional study design, we were unable to include existing contraindications for antithrombotic therapy or indications for initiating therapy.

5. Future Directions

Further research with a larger sample size and a longitudinal design is needed to better understand how comorbidity burden and prior antithrombotic therapy influence stroke severity. Future studies could also investigate how the duration of antithrombotic therapy affects stroke outcomes, or other treatment options, such as early rhythm control, may influence the outcome of these patients [42]. The role of screening for atrial fibrillation can be improved by utilizing modern technology, which may aid in developing more accurate stroke prediction models [43]. Research and clinical trials have shown that DOACs are not efficacious in some clinical scenarios where warfarin is still useful in stroke prevention (e.g., valvular atrial fibrillation, mechanical heart valves, embolic strokes of undetermined source, or antiphospholipid syndrome) [44].

6. Conclusions

Our study showed that first-ever ischemic stroke due to atrial fibrillation was more common in women in our cohort. Subjects on prior anticoagulant therapy (warfarin) had more favorable outcomes at discharge.

Author Contributions

Conceptualization, I.M. and H.B.; methodology, I.M. and H.B.; validation, H.B.; formal analysis, I.M., D.V., P.Č., C.S. and H.B.; investigation, I.M., D.V., P.Č., C.S. and H.B.; writing—original draft, I.M.; Writing—review & editing, I.M., D.V., P.Č., C.S. and H.B.; visualization, I.M.; Supervision, H.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committees, namely The Ethics Committee of the Faculty of Medicine Osijek (protocol code: 2158-61-07-21-70; date of approval: 14 April 2021) and The Ethics Committee of the Sveti Duh University Hospital (protocol code: 012-8046/1; date of approval: 30 December 2020).

Informed Consent Statement

Patient consent was waived due to the study design (retrospective study).

Data Availability Statement

The data presented in this study are only available upon request to the corresponding author for ethical reasons.

Acknowledgments

We thank Susanna Walker (USA) for her diligent proofreading of the English-language content this manuscript.

Conflicts of Interest

H.B. declares speaker’s fees from Bayer, Boehringer Ingelheim, Viatris, Novartis, Pliva-Teva, Abbott, Medis, Eli Lilly, Berlin Chemie, Pfizer, and Roche. The other authors declare no conflicts of interest.

References

  1. Babkair, L.A. Cardioembolic Stroke: A Case Study. Crit. Care Nurse 2017, 37, 27–39. [Google Scholar] [CrossRef] [PubMed]
  2. Tracz, J.; Gorczyca-Glowacka, I.; Rosolowska, A.; Wozakowska-Kaplon, B. Long-Term Outcomes after Stroke in Patients with Atrial Fibrillation: A Single Center Study. Int. J. Environ. Res. Public Health 2023, 20, 3491. [Google Scholar] [CrossRef] [PubMed]
  3. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet 1994, 343, 687–691. [CrossRef]
  4. Freedman, B.; Potpara, T.S.; Lip, G.Y. Stroke prevention in atrial fibrillation. Lancet 2016, 388, 806–817. [Google Scholar] [CrossRef] [PubMed]
  5. Lip, G.Y.; Nieuwlaat, R.; Pisters, R.; Lane, D.A.; Crijns, H.J. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The euro heart survey on atrial fibrillation. Chest 2010, 137, 263–272. [Google Scholar] [CrossRef] [PubMed]
  6. Fox, C.K.; Kamel, H. Congenital Heart Disease, Atrial Fibrillation, and Ischemic Stroke Risk. J. Am. Heart Assoc. 2024, 13, e036458. [Google Scholar] [CrossRef] [PubMed]
  7. Fauchier, L.; Clementy, N.; Bisson, A.; Ivanes, F.; Angoulvant, D.; Babuty, D.; Lip, G.Y. Should Atrial Fibrillation Patients With Only 1 Nongender-Related CHA2DS2-VASc Risk Factor Be Anticoagulated? Stroke 2016, 47, 1831–1836. [Google Scholar] [CrossRef] [PubMed]
  8. Hindricks, G.; Potpara, T.; Dagres, N.; Arbelo, E.; Bax, J.J.; Blomstrom-Lundqvist, C.; Boriani, G.; Castella, M.; Dan, G.A.; Dilaveris, P.E.; et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur. Heart J. 2021, 42, 373–498. [Google Scholar] [CrossRef] [PubMed]
  9. Hart, R.G.; Pearce, L.A.; Aguilar, M.I. Meta-analysis: Antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann. Intern. Med. 2007, 146, 857–867. [Google Scholar] [CrossRef] [PubMed]
  10. Franc, D.; Sanak, D.; Kral, M.; Hutyra, M.; Taborsky, M.; Divisova, P.; Zapletalova, J. Impact of prior oral anticoagulation on admission stroke severity in patients with atrial fibrillation. Biomed. Pap. 2024. [Google Scholar] [CrossRef] [PubMed]
  11. Hylek, E.M.; Go, A.S.; Chang, Y.; Jensvold, N.G.; Henault, L.E.; Selby, J.V.; Singer, D.E. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N. Engl. J. Med. 2003, 349, 1019–1026. [Google Scholar] [CrossRef] [PubMed]
  12. O’Donnell, M.; Oczkowski, W.; Fang, J.; Kearon, C.; Silva, J.; Bradley, C.; Guyatt, G.; Gould, L.; D’Uva, C.; Kapral, M.; et al. Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: An observational study. Lancet Neurol. 2006, 5, 749–754. [Google Scholar] [CrossRef] [PubMed]
  13. Carnicelli, A.P.; Hong, H.; Connolly, S.J.; Eikelboom, J.; Giugliano, R.P.; Morrow, D.A.; Patel, M.R.; Wallentin, L.; Alexander, J.H.; Cecilia Bahit, M.; et al. Direct Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials With Interaction Testing by Age and Sex. Circulation 2022, 145, 242–255. [Google Scholar] [CrossRef] [PubMed]
  14. Mogashoa, V.; Mpanya, D.; Tsabedze, N. Anticoagulation control for nonvalvular atrial fibrillation in a tertiary academic centre in Johannesburg. Thromb. J. 2024, 22, 94. [Google Scholar] [CrossRef] [PubMed]
  15. Benz, A.P.; Meinel, T.R.; Salerno, A.; Beyeler, M.; Strambo, D.; Kaesmacher, J.; Polymeris, A.A.; Kahles, T.; Katan, M.; Engelter, S.T.; et al. Prevalence and Distribution of Intracranial Vessel Occlusion on Angiography and Its Association with Functional Outcome in Patients with Atrial Fibrillation Presenting with Ischemic Stroke. Ann. Neurol. 2024, 96, 1115–1123. [Google Scholar] [CrossRef] [PubMed]
  16. Ujjin, A.; Wongcharoen, W.; Suwanagool, A.; Chai-Adisaksopha, C. Optimal Strategies to Select Warfarin Dose for Thai Patients with Atrial Fibrillation. J. Clin. Med. 2024, 13, 2675. [Google Scholar] [CrossRef] [PubMed]
  17. Anduaga, I.; Affronti, A.; Cepas-Guillen, P.; Alcocer, J.; Flores-Umanzor, E.; Regueiro, A.; Brugaletta, S.; Quintana, E.; Sanchis, L.; Sabate, M.; et al. Non-Pharmacological Stroke Prevention in Atrial Fibrillation. J. Clin. Med. 2023, 12, 5524. [Google Scholar] [CrossRef] [PubMed]
  18. Bamford, J.; Sandercock, P.; Dennis, M.; Burn, J.; Warlow, C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991, 337, 1521–1526. [Google Scholar] [CrossRef] [PubMed]
  19. Broderick, J.P.; Adeoye, O.; Elm, J. Evolution of the Modified Rankin Scale and Its Use in Future Stroke Trials. Stroke 2017, 48, 2007–2012. [Google Scholar] [CrossRef] [PubMed]
  20. Roquer, J.; Campello, A.R.; Gomis, M. Sex differences in first-ever acute stroke. Stroke 2003, 34, 1581–1585. [Google Scholar] [CrossRef] [PubMed]
  21. Arboix, A.; Oliveres, M.; Garcia-Eroles, L.; Maragall, C.; Massons, J.; Targa, C. Acute cerebrovascular disease in women. Eur. Neurol. 2001, 45, 199–205. [Google Scholar] [CrossRef] [PubMed]
  22. Friberg, J.; Scharling, H.; Gadsboll, N.; Truelsen, T.; Jensen, G.B. Comparison of the impact of atrial fibrillation on the risk of stroke and cardiovascular death in women versus men (The Copenhagen City Heart Study). Am. J. Cardiol. 2004, 94, 889–894. [Google Scholar] [CrossRef] [PubMed]
  23. Westerman, S.; Wenger, N. Gender Differences in Atrial Fibrillation: A Review of Epidemiology, Management, and Outcomes. Curr. Cardiol. Rev. 2019, 15, 136–144. [Google Scholar] [CrossRef] [PubMed]
  24. Sposato, L.A.; Cipriano, L.E.; Saposnik, G.; Ruiz Vargas, E.; Riccio, P.M.; Hachinski, V. Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: A systematic review and meta-analysis. Lancet Neurol. 2015, 14, 377–387. [Google Scholar] [CrossRef] [PubMed]
  25. Milman, B.; Burns, B.D. Atrial fibrillation: An approach to diagnosis and management in the emergency department. Emerg. Med. Pract. 2021, 23, 1–28. [Google Scholar] [PubMed]
  26. Patti, G.; Lucerna, M.; Pecen, L.; Siller-Matula, J.M.; Cavallari, I.; Kirchhof, P.; De Caterina, R. Thromboembolic Risk, Bleeding Outcomes and Effect of Different Antithrombotic Strategies in Very Elderly Patients with Atrial Fibrillation: A Sub-Analysis From the PREFER in AF (PREvention oF Thromboembolic Events-European Registry in Atrial Fibrillation). J. Am. Heart Assoc. 2017, 6, e005657. [Google Scholar] [CrossRef] [PubMed]
  27. Jung, Y.H.; Kim, Y.D.; Kim, J.; Han, S.W.; Oh, M.S.; Lee, J.S.; Lee, K.Y. Initial Stroke Severity in Patients With Atrial Fibrillation According to Antithrombotic Therapy Before Ischemic Stroke. Stroke 2020, 51, 2733–2741. [Google Scholar] [CrossRef] [PubMed]
  28. Tu, H.T.; Campbell, B.C.; Christensen, S.; Desmond, P.M.; De Silva, D.A.; Parsons, M.W.; Churilov, L.; Lansberg, M.G.; Mlynash, M.; Olivot, J.M.; et al. Worse stroke outcome in atrial fibrillation is explained by more severe hypoperfusion, infarct growth, and hemorrhagic transformation. Int. J. Stroke 2015, 10, 534–540. [Google Scholar] [CrossRef] [PubMed]
  29. Kimura, K.; Minematsu, K.; Yamaguchi, T. Atrial fibrillation as a predictive factor for severe stroke and early death in 15,831 patients with acute ischaemic stroke. J. Neurol. Neurosurg. Psychiatry 2005, 76, 679–683. [Google Scholar] [CrossRef] [PubMed]
  30. Jackson, C.; Sudlow, C. Are lacunar strokes really different? A systematic review of differences in risk factor profiles between lacunar and nonlacunar infarcts. Stroke 2005, 36, 891–901. [Google Scholar] [CrossRef] [PubMed]
  31. Dulli, D.A.; Stanko, H.; Levine, R.L. Atrial fibrillation is associated with severe acute ischemic stroke. Neuroepidemiology 2003, 22, 118–123. [Google Scholar] [CrossRef] [PubMed]
  32. Freitas-Silva, M.; Medeiros, R.; Nunes, J.P.L. Risk factors among stroke subtypes and its impact on the clinical outcome of patients of Northern Portugal under previous aspirin therapy. Clin. Neurol. Neurosurg. 2021, 203, 106564. [Google Scholar] [CrossRef] [PubMed]
  33. Miller, V.T.; Rothrock, J.F.; Pearce, L.A.; Feinberg, W.M.; Hart, R.G.; Anderson, D.C. Ischemic stroke in patients with atrial fibrillation: Effect of aspirin according to stroke mechanism. Stroke Prevention in Atrial Fibrillation Investigators. Neurology 1993, 43, 32–36. [Google Scholar] [CrossRef] [PubMed]
  34. Wang, C.; Wang, Y.; Zhao, X.; Liu, L.; Liu, G.; Wang, D.Z.; Li, H. Anticoagulation-related reduction of first-ever stroke severity in Chinese patients with atrial fibrillation. J. Clin. Neurosci. 2014, 21, 1755–1760. [Google Scholar] [CrossRef] [PubMed]
  35. Xian, Y.; O’Brien, E.C.; Liang, L.; Xu, H.; Schwamm, L.H.; Fonarow, G.C.; Bhatt, D.L.; Smith, E.E.; Olson, D.M.; Maisch, L.; et al. Association of Preceding Antithrombotic Treatment With Acute Ischemic Stroke Severity and In-Hospital Outcomes Among Patients With Atrial Fibrillation. JAMA 2017, 317, 1057–1067. [Google Scholar] [CrossRef] [PubMed]
  36. Khanevski, A.N.; Bjerkreim, A.T.; Novotny, V.; Naess, H.; Thomassen, L.; Logallo, N.; Kvistad, C.E. Recurrent ischemic stroke: Incidence, predictors, and impact on mortality. Acta Neurol. Scand. 2019, 140, 3–8. [Google Scholar] [CrossRef] [PubMed]
  37. Paciaroni, M.; Agnelli, G.; Falocci, N.; Caso, V.; Becattini, C.; Marcheselli, S.; Rueckert, C.; Pezzini, A.; Poli, L.; Padovani, A.; et al. Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study. Stroke 2015, 46, 2175–2182. [Google Scholar] [CrossRef] [PubMed]
  38. Hannon, N.; Arsava, E.M.; Audebert, H.J.; Ay, H.; Crowe, M.; Ni Chroinin, D.; Furie, K.; McGorrian, C.; Molshatzki, N.; Murphy, S.; et al. Antithrombotic treatment at onset of stroke with atrial fibrillation, functional outcome, and fatality: A systematic review and meta-analysis. Int. J. Stroke 2015, 10, 808–814. [Google Scholar] [CrossRef] [PubMed]
  39. Park, J.M.; Kang, K.; Cho, Y.J.; Hong, K.S.; Lee, K.B.; Park, T.H.; Lee, S.J.; Ko, Y.; Han, M.K.; Lee, J.; et al. Comparative Effectiveness of Prestroke Aspirin on Stroke Severity and Outcome. Ann. Neurol. 2016, 79, 560–568. [Google Scholar] [CrossRef] [PubMed]
  40. Kim, W.J.; Ko, Y.; Yang, M.H.; Im, S.H.; Park, J.H.; Lee, J.; Han, M.K.; Bae, H.J. Differential effect of previous antiplatelet use on stroke severity according to stroke mechanism. Stroke 2010, 41, 1200–1204. [Google Scholar] [CrossRef] [PubMed]
  41. Choudhury, A.; Lip, G.Y. Atrial fibrillation and the hypercoagulable state: From basic science to clinical practice. Pathophysiol. Haemost. Thromb. 2003, 33, 282–289. [Google Scholar] [CrossRef] [PubMed]
  42. Jensen, M.; Suling, A.; Metzner, A.; Schnabel, R.B.; Borof, K.; Goette, A.; Haeusler, K.G.; Zapf, A.; Wegscheider, K.; Fabritz, L.; et al. Early rhythm-control therapy for atrial fibrillation in patients with a history of stroke: A subgroup analysis of the EAST-AFNET 4 trial. Lancet Neurol. 2023, 22, 45–54. [Google Scholar] [CrossRef] [PubMed]
  43. Kato, Y.; Tsutsui, K.; Nakano, S.; Hayashi, T.; Suda, S. Cardioembolic Stroke: Past Advancements, Current Challenges, and Future Directions. Int. J. Mol. Sci. 2024, 25, 5777. [Google Scholar] [CrossRef] [PubMed]
  44. Ageno, W.; Caramelli, B.; Donadini, M.P.; Girardi, L.; Riva, N. Changes in the landscape of anticoagulation: A focus on direct oral anticoagulants. Lancet Haematol. 2024, 11, e938–e950. [Google Scholar] [CrossRef] [PubMed]
Medicines 12 00018 g001
Figure 1. Box plot diagram (median, IQR) representing the distribution of NIHSS scores across groups of subjects with different types of prior antithrombotic therapy.
Figure 1. Box plot diagram (median, IQR) representing the distribution of NIHSS scores across groups of subjects with different types of prior antithrombotic therapy.
Medicines 12 00018 g001
Medicines 12 00018 g002
Figure 2. Box plot diagram (median, IQR) representing distribution of mRS scores across groups of subjects with different types of prior antithrombotic therapy.
Figure 2. Box plot diagram (median, IQR) representing distribution of mRS scores across groups of subjects with different types of prior antithrombotic therapy.
Medicines 12 00018 g002
Table 1. Differences in characteristics of subjects according to risk factors and stroke localization to type of prior antithrombotic therapy.
Table 1. Differences in characteristics of subjects according to risk factors and stroke localization to type of prior antithrombotic therapy.
CharacteristicsAnticoagulant Therapy (a)Antiplatelet Therapy (b)Without Antithrombotic Therapy (c)p *
Gender [n (%)]
female76 (62.3)128 (61)276 (65.4)0.52
male46 (37.7)82 (39)146 (34.6)
Age [median, (IQR)]76 (71–81)80 (75–84)80 (74–84)0.001 †
Arterial hypertension [n (%)]112 (91.8)196 (93.3)359 (85.1)0.004 ‡
Hyperlipidemia [n (%)]67 (54.9)97 (46.2)167 (39.6)0.008 §
Diabetes mellitus [n (%)]42 (34.4)83 (39.5)121 (28.7)0.02 ||
Cardiomyopathy [n (%)]89 (73)159 (75.7)265 (62.8)0.002
CHADS2 score [median (IQR)]3 (2–3)3 (2–3)3 (2–3)<0.001 **
OCSPTACI24 (19.7)36 (17.1)48 (11.4)0.116
PACI51 (41.8)105 (50)225 (53.3)
LACI24 (19.7)38 (18.1)72 (17.1)
POCI23 (18.9)31 (14.8)77 (18.2)
IQR, interquartile range; OCSP, Oxfordshire Community Stroke Project; TACI, total anterior circulation infarct; PACI, partial anterior circulation infarct; LACI, lacunar circulation infarct; POCI, posterior circulation infarct; * χ2 test; † Kruskal–Wallis test (pairwise comparison) of significant differences ((a) vs. (b) and (a) vs. (c)); ‡ adjusted residuals 1.3 (a), 2.6 (b), −3.3 (c); the significant adjusted p-value p = 0.009 (b), p = 0.001 (c); § adjusted residuals 2.7 (a), 0.8 (b), −2.7 (c); the significant adjusted p-value p = 0.007 (a), p = 0.007 (c); || adjusted residuals 0.5 (a), 2.5 (b), −2.6 (c); the significant adjusted p-value p = 0.012 (b), p = 0.009 (c); adjusted residuals 1.3 (a), 2.8 (b), −3.5 (c); the significant adjusted p-value p = 0.005 (b), p < 0.001 (c); ** Kruskal–Wallis test (pairwise comparison); the significant difference (a) vs. (b) and (b) vs. (c).
Table 2. Distribution of subjects regarding CHADS2 rating scale in relation to type of prior antithrombotic therapy and previously known atrial fibrillation.
Table 2. Distribution of subjects regarding CHADS2 rating scale in relation to type of prior antithrombotic therapy and previously known atrial fibrillation.
Previous AF[n (%)]CHADS2 ≤ 1CHADS2 ≥ 2
UnknownAnticoagulant therapy1 (2.6)1 (0.5)
Antiplatelet therapy1 (2.6)48 (24.5)
Without antithrombotic therapy36 (94.7)147 (75)
KnownAnticoagulant therapy13 (25.5)213 (45.4)
Antiplatelet therapy12 (23.5)149 (31.8)
Without antithrombotic therapy26 (51)107 (22.8)
AF—atrial fibrillation.
Table 3. Differences in stroke outcome based on mRS scale across groups of subjects with different types of prior antithrombotic therapy (mRS, modified Rankin scale).
Table 3. Differences in stroke outcome based on mRS scale across groups of subjects with different types of prior antithrombotic therapy (mRS, modified Rankin scale).
mRS [n (%)]Anticoagulant Therapy (a)Antiplatelet Therapy (b)Without Antithrombotic Therapy (c)p *
mRS ≤ 117 (13.9)18 (8.6)50 (11.8)
Adjusted residual1.0−1.50.6
2 ≤ mRS ≤ 343 (35.2)43 (20.5)104 (24.6)
Adjusted residual2.8−1.9−0.40.025
4 ≤ mRS ≤ 534 (27.9)80 (38.1)153 (36.3)
Adjusted residual−1.91.00.5
mRS = 628 (23)69 (32.9)115 (27.3)
Adjusted residual−1.41.8−0.6
* χ2 test.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Maduna, I.; Vidaković, D.; Črnac, P.; Saleh, C.; Budinčević, H. First-Ever Stroke Outcomes in Patients with Atrial Fibrillation: A Retrospective Cross-Sectional Study. Medicines 2025, 12, 18. https://doi.org/10.3390/medicines12030018

AMA Style

Maduna I, Vidaković D, Črnac P, Saleh C, Budinčević H. First-Ever Stroke Outcomes in Patients with Atrial Fibrillation: A Retrospective Cross-Sectional Study. Medicines. 2025; 12(3):18. https://doi.org/10.3390/medicines12030018

Chicago/Turabian Style

Maduna, Ivanka, Dorotea Vidaković, Petra Črnac, Christian Saleh, and Hrvoje Budinčević. 2025. "First-Ever Stroke Outcomes in Patients with Atrial Fibrillation: A Retrospective Cross-Sectional Study" Medicines 12, no. 3: 18. https://doi.org/10.3390/medicines12030018

APA Style

Maduna, I., Vidaković, D., Črnac, P., Saleh, C., & Budinčević, H. (2025). First-Ever Stroke Outcomes in Patients with Atrial Fibrillation: A Retrospective Cross-Sectional Study. Medicines, 12(3), 18. https://doi.org/10.3390/medicines12030018

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop