Next Article in Journal
Mildly Reduced Doses of Adrenaline Do Not Affect Key Hemodynamic Parameters during Cardio-Pulmonary Resuscitation in a Pig Model of Cardiac Arrest
Previous Article in Journal
Defining NASH from a Multi-Omics Systems Biology Perspective
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
JCM
Volume 10
Issue 20
10.3390/jcm10204670
jcm-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 thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Lack of Sex Disparity in Oral Anticoagulation in Atrial Fibrillation Patients Presenting with Ischemic Stroke in a Rural Population

by
Eric Koza
1,†,
Johan Diaz
1,†,
Durgesh Chaudhary
2,
Shima Shahjouei
2,
Jiang Li
3,
Vida Abedi
3,4 and
Ramin Zand
2,*
1
Geisinger Commonwealth School of Medicine, Scranton, PA 18510, USA
2
Department of Neurology, Neuroscience Institute, Geisinger Health System, 100 North Academy Ave, Danville, PA 17822, USA
3
Department of Molecular and Functional Genomics, Geisinger Health System, Danville, PA 17822, USA
4
Biocomplexity Institute, Virginia Tech, Blacksburg, VA 24061, USA
*
Author to whom correspondence should be addressed.
†
Contributed equally.
J. Clin. Med. 2021, 10(20), 4670; https://doi.org/10.3390/jcm10204670
Submission received: 27 August 2021 / Revised: 30 September 2021 / Accepted: 30 September 2021 / Published: 12 October 2021
(This article belongs to the Section Vascular Medicine)
Browse Figures
Review Reports Versions Notes

Abstract

:
Various studies on oral anticoagulants (OAC) use among atrial fibrillation (AF) patients have shown high rates of undertreatment and the presence of sex disparity. This study used the ‘Geisinger Neuroscience Ischemic Stroke’ (GNSIS) database to examine sex differences in OAC treatment among ischemic stroke patients with the pre-event diagnosis of AF in rural Pennsylvania between 2004 and 2019. We examined sex disparities in OAC undertreatment and associated risks based on age group and ischemic stroke year. A total of 1062 patients were included in the study and 1015 patients (96%) had CHA2DS2-VASc score ≥ 2, of which 549 (54.1%) were women. Undertreatment rates were not statistically significant between men and women in the overall cohort (50.0% vs. 54.5%, p = 0.18), and male sex was not found to be a significant factor in undertreatment (OR 0.82, 95% CI 0.62–1.09, p = 0.17). The result persisted even when patients were divided into four age groups and two groups based on the study time period. The undertreatment rates in both sex groups remained consistent following the introduction of novel oral anticoagulants. In conclusion, there was no evidence of sex disparity with respect to OAC treatment, even after stratifying the cohort by age and ischemic stroke year.

1. Introduction

Atrial fibrillation (AF) is a major risk factor for stroke incidence and the most significant cardiac arrhythmia worldwide [1,2]. It is estimated that around 7.6 million Americans have suffered a stroke, with women carrying a higher lifetime risk when compared to men [2]. The increased risk in women has been translated to the clinical practice through the inclusion of female sex within risk stratification models for stroke management, such as the CHA2DS2-VASc score [3,4,5,6]. Current guidelines by the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) recommend oral anticoagulation (OAC) therapy for all AF patients with a CHA2DS2-VASc ≥ 2, and those with a CHA2DS2-VASc of 1 should be considered for treatment with OAC or antiplatelets [3].
Despite the AHA/ACC/HRS guidelines for the management of patients with atrial fibrillation [3], some studies have suggested that women have a higher risk of OAC undertreatment than men [7,8,9,10], while others have reported no significant differences [11,12]. A previous study using a national registry in the United States found that women had a higher risk of undertreatment across all CHA2DS2-VASc scores [9], while an investigation in Europe found that a higher proportion of female patients received OAC treatment in contrast to males [13]. Further, a recent international study found no differences in anticoagulation use between women and men globally except for a sex disparity specific to North America [11]. While the authors attributed these results to differences in guideline recommendations [11], there is still uncertainty about sex inequalities in OAC treatment due to the combined contradictory findings.
In a previous study, we investigated the prevalence and factors associated with AF undertreatment in patients with stroke outcomes [14]. The current analysis aimed to determine whether sex influenced AF treatment among a rural population of stroke patients in central and northeast Pennsylvania, USA. The study examined sex disparities by evaluating undertreatment rates and risk associations, stratifying patients based on age groups and index stroke dates, mainly considering the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) in 2010.

2. Materials and Methods

2.1. Data Source and Study Population

The study used a retrospective cohort analyzing data from the “Geisinger Neuroscience Ischemic Stroke (GNSIS)” registry, a database of ischemic stroke patients at Geisinger which includes demographics, family history, and clinical and past medical history. Geisinger is an integrated system delivering healthcare in rural Pennsylvania to approximately 2.6 million people throughout 43 counties. Patients were included in GNSIS if they had a primary diagnosis of ischemic stroke based on the International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9-CM or ICD-10-CM) during a hospital encounter of at least 24 h, and a magnetic resonance imaging of the brain in the same encounter. Further details on the data extraction and pre-processing for the GNSIS database are provided in previously published study articles [14,15,16]. The Geisinger Institutional Review Board reviewed and approved this study as a “non-human subject research” for using de-identified information.

2.2. Evaluation of Sex Disparities

The study included ischemic stroke patients ≥ 18 years old with an AF diagnosis ICD (ICD-9-CM and ICD-10-CM) code at any time before the stroke index date, and it excluded patients with an AF diagnosis on the index stroke date. The study analyzed point prevalence among men and women, and patients’ distribution according to CHA2DS2-VASc score. Sex was studied as a risk factor for undertreatment in patients with CHA2DS2-VASc ≥ 2 stratified based on age group or NOACs use. Alternatively, CHADS2 was employed for risk stratification with a score of ≥2 denoting patients at high risk of stroke.
To study the impact of NOACs on sex disparity in undertreatment, patients were stratified based on their index stroke date. The first group contained patients with an index stroke date between 2004 and 2010, while the second group included patients with an index stroke date between 2011 and 2019. To examine the sex disparity in OAC treatment in different age groups, the patients were also divided into four subgroups based on age, and undertreatment was examined in each subgroup.
The HAS-BLED score is used by clinicians to evaluate the risk of bleeding in AF patients and assesses the history of uncontrolled hypertension, renal or liver disease, stroke, bleeding, labile INR, age ≥ 65 years, medications, and alcohol use [3]. For this study, a limited HAS-BLED score was calculated from the liver and renal function, age, medications predisposing to bleeding, and history of stroke, TIA, and bleeding diagnoses. The differences in the limited HAS-BLED scores between the male and female patients were examined along with its association with sex disparity in undertreatment.

2.3. Statistical Analysis

In the study, demographic and comorbidity characteristics for the population were summarized using descriptive statistics. Continuous variables were presented as mean ± standard deviation or median with interquartile range (IQR), and categorical variables were presented as counts and percentages. Statistical analysis among groups included Pearson’s chi-squared test or Fisher’s exact test for the categorical variables, and analysis of variance (ANOVA) or the Kruskal–Wallis test for continuous variables. Multiple logistic regression was performed to examine the association of gender with undertreatment in AF patients, adjusting for age and comorbidities, while the goodness of fit was evaluated using the Hosmer–Lemeshow test. Variables with missingness, such as the National Institutes of Health Stroke Scale (NIHSS), were not included in regression analysis. The alpha value for all p-values was set to 0.05. R version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria) was used for all statistical analyses.

3. Results

3.1. Patient Characteristics of Study Population

Evaluation of ischemic stroke patients from the GNSIS database yielded 1062 patients with an AF diagnosis before the index stroke date (Figure 1). Of these patients, 506 (47.6%) were men, and 556 (52.4%) were women (Table 1). The median age at AF diagnosis was 72.3 years (IQR 64.4–79.2) for men and 78.9 years (IQR 69.8–84.5) for women (p < 0.001). The median age at the index date of stroke was 76.9 years (IQR 68.1–82.9) for men and 82.6 years (IQR 74.9–88.3) for women (p < 0.001). Additional patient characteristics are summarized in Table 1. In terms of medication, there were no significant differences between men and women using antiplatelets only (116 (22.9%) vs. 115 (20.7%); p = 0.418), anticoagulants only (129 (25.5%) vs. 146 (26.3%); p = 0.830), or anticoagulants and antiplatelets (120 (23.7%) vs. 106 (19.1%); p = 0.076). There was a significant difference between the CHA2DS2-VASc median score (male median, 4; IQR, 3–5 vs. female median, 5; IQR, 4–6; p < 0.001). Further comparison of CHA2DS2-VASc scores distribution based on sex can be seen in Figure 2.

3.2. Undertreatment of Atrial Fibrillation

After dividing the distribution of CHA2DS2-VASc into three categories, 0, 1, and 2+ (Table 1), 1015 (95.6%) patients were included in the 2+ category. Of the 1015 patients, 466 (45.9%) were men, and 549 (54.1%) were women (Figure 1). Further evaluation of these patients showed that based on current treatment guidelines, 233 (50.0%) men were not receiving adequate therapy, while 299 (54.5%) women were also not receiving adequate therapy (p = 0.18), as seen in Table 2. Overall, the male sex was not found to have a statistically significant association with undertreatment in multiple logistic regression (OR 0.82, 95% CI 0.62–1.09, p = 0.17) (Figure 3).

3.3. Anticoagulant Undertreatment Rate Based for Different Age Groups

To examine sex differences in atrial fibrillation, patients were first stratified into four groups based on age quartiles (Table 2). Group 1 consisted of 254 patients aged 44.4–72.8 years, Group 2 had 254 patients aged 72.8–80.6 years, Group 3 included 254 patients aged 80.6–86.6 years, and Group 4 with 253 patients older than 86.6 years. The OAC undertreatment rate was not significantly different in any of the four age groups (Table 2), nor was male sex a significant predictor in the multiple logistic regression on undertreatment (Figure 3).

3.4. Anticoagulant Undertreatment Rate Based on Index Stroke Year

When grouping the patients based on the index stroke year, the first group (2004–2010) contained 221 patients with 112 (50.7%) identified as undertreated with anticoagulants, 58 (51.3%) men, and 54 (50.0%) women (Table 2). Undertreatment rates between the sexes did not show a statistically significant difference (p = 0.95). Additionally, sex was not associated with undertreatment rate (OR 1.46, 95% CI 0.75–2.87, p = 0.26) in Figure 3. In the second group (2011–2019), there were 794 patients, of which 420 (52.9%) were undertreated with anticoagulants, 175 (49.6%) men and 245 (55.6%) women (Table 2). No statistically significant difference was observed between the undertreatment of men and women (p = 0.11) in Table 2, nor with the association of male sex and undertreatment in multiple logistic regression (OR 0.73, CI 0.53–1.01, p = 0.06) in Figure 3. Overall, undertreatment rates following the introduction of NOACs were comparable to previous years without significant differences in OAC usage between sex groups.

4. Discussion

The results from our rural AF patient population with ischemic stroke outcomes indicate the presence of undertreatment according to guideline-recommended OAC of about 50% in men and 55% in women with a CHA2DS2-VASc ≥ 2; however, sex was not shown to be a statistically significant risk factor for OAC undertreatment. When dividing the population based on age and index stroke year, both analyses revealed no apparent sex disparity and no risk association between sex and undertreatment. Following the introduction of NOACs in 2010, the undertreatment rates remained consistent between the 2004–2010 and 2010–2019 groups, without significant sex disparities or associated risk. Similarly, risk stratification using CHADS2 scores did not show a sex disparity or risk association with undertreatment (Supplemental Result R1, Table S1). Several associated factors were more prevalent in men, such as dyslipidemia, diabetes, peripheral vascular disease, and a history of myocardial infarction. Women were diagnosed with AF at an older age, had an older age at index stroke date, and a higher median baseline CHA2DS2-VASc, which aligned with populations in similar studies [5,9,10,12,13,17,18].
In contrast, recent studies have identified potential sex disparities in OAC undertreatment (Supplemental Table S2). Retrospectives studies have found lower odds of OAC initiation and an increased likelihood of undertreatment among high-risk female patients with Medicare and commercial insurance [7,8]. Similarly, a study using the PINNACLE National Cardiovascular Data Registry found that women had a higher risk of undertreatment across all levels of the CHA2DS2-VASc scores [9], while a study from the Euro Observational Research Programme Pilot survey on atrial fibrillation (EORP-AF) reported that more women with CHA2 DS2-VASc ≥ 2 received OAC than men [13]. However, other researchers have found comparable results to those presented in this study (Supplemental Table S2). A prospective cohort study in China reported no sex difference in OAC treatment among AF patients with CHA2DS2-VASc ≥ 2, but women represented a smaller percentage of the patient population [12]. Two international studies found no significant sex disparities in OAC therapy worldwide [11,19]. In one of these studies, the authors described a sex disparity specific to North America that was attributed to differences in thresholds for OAC initiation due to varying guideline recommendations [11].
Our statistical analysis and logistic regression models of undertreatment showed no association for male sex with a decreased risk of OAC undertreatment, differing from previous studies (Supplemental Table S2). Two investigations in Italy and Sweden stratified AF patients based on age and year cohorts found that women in the ≥75 age group had an increased risk of OAC undertreatment, even with the emergence of NOACs and updated European Society of Cardiology Guidelines [10,20,21,22]. In general, prior studies concur that increasing age seems to correlate to an increased risk of AF undertreatment, especially among patients ≥70 or 80 years old [23,24,25,26,27]. There have been reports of an aging paradox, where patients ≥70 or 80 years old were less likely to receive OAC therapy despite a heightened risk of stroke [23,24,25,26,27]. Our previous study using the GNSIS registry found that less than half of our high-risk patients received OAC treatment according to guidelines [14]. These results were comparable to other studies in the USA [23,24]. However, we did not observe an increased risk of undertreatment associated with age [14].
There were several strengths and limitations present within our study. The EHR data collected provided a wealth of variables for each patient, as well as a wide time frame for evaluation, allowing a more robust analysis of differences in patient characteristics between sexes. While we had a large cohort comprised of patients from multiple study centers, our cohort lacked racial and socioeconomic diversity seen in previous related studies [7,9,10,17], in addition to the patient population being restricted to only rural areas, thus possibly limiting the external validity of our results.
Another limitation may be the use of CHA2 DS2-VASc to assess stroke risk and undertreatment rates in AF patients from 2004 to 2019. In the United States, CHA2 DS2-VASc was implemented in 2014, and prior to this guideline update, CHADS2 was used for risk stratification [3]. However, in our previous study, we found similar undertreatment rates using CHA2 DS2-VASc and CHADS2 scores [14], and our results in this study are consistent even when using CHADS2 for risk stratification. Other limitations include the lack of a complete HAS-BLED score (Supplemental Results R2), used by clinicians to identify patients at risk for bleeding [3,6,28] and to potentially examine sex disparities [7,8,9,11,13,19].
Lastly, the use of ICD-9-CM and ICD-10-CM posed potential constraints. AF diagnosis was measured using ICD codes without electrocardiogram (EKG) confirmation. Furthermore, ICD codes do not provide detailed clinical information and sex-related preferences. Previous studies have found that women tend to present with more symptoms, older age, and receive more conservative treatments [12,13]. Additionally, ICD codes fail to give insight into other possible external factors affecting treatment, such as specific patient and physician preferences, and the decision process in treatment choice, as well as accurate insurance information. While medication data in EHR can provide information on whether a patient was prescribed a certain medication, determining the patient compliance remains a challenge [29].

5. Conclusions

This study found that OAC treatment for AF in ischemic stroke patients remains low according to guidelines in both men and women; however, there does not appear to be a sex disparity, even when stratifying patients by age and index ischemic stroke date. Sex was not associated with OAC undertreatment in our rural population.

Supplementary Materials

The following are available online at https://www.mdpi.com/article/10.3390/jcm10204670/s1, Result R1. Risk stratification by CHADS2 score, Table S1. Anticoagulant undertreatment rates and logistic regression for patients with a CHADS2 score ≥ 2 stratified, Result R2. Risk of bleeding using limited HAS-BLED, Table S2. Summary of Relevant Studies.

Author Contributions

Conceptualization, R.Z.; Data curation, D.C.; Formal analysis, E.K., J.D., D.C., S.S., J.L., V.A. and R.Z.; Investigation, E.K., J.D. and D.C.; Methodology, J.L., V.A. and R.Z.; Supervision, V.A. and R.Z.; Writing—original draft, E.K. and J.D.; Writing—review & editing, D.C., S.S., J.L., V.A. and R.Z. All authors have read and agreed to the published version of the manuscript.

Funding

This study had no specific funding. VA had financial research support from the National Institute of Health (NIH) grant No. R56HL116832 sub-awarded to Geisinger during the study period. RZ had financial research support from Bucknell University Initiative Program, Roche—Genentech Biotechnology Company, the Geisinger Health Plan Quality fund, and receives institutional support from Geisinger Health System during the study period. The funders had no role in the study design, data collection, and analysis, or preparation of the manuscript.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Geisinger Institutional Review Board (IRB No. 2019-0470, 5/22/2019).

Informed Consent Statement

Patient consent was waived as the study only utilized de-identified data.

Data Availability Statement

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to institutional policies requiring data-sharing agreement.

Conflicts of Interest

The authors declare no competing interest.

References

  1. Chugh, S.S.; Havmoeller, R.; Narayanan, K.; Singh, D.; Rienstra, M.; Benjamin, E.; Gillum, R.F.; Kim, Y.-H.; McAnulty, J.H.; Zheng, Z.-J.; et al. Worldwide Epidemiology of Atrial Fibrillation: A Global Burden of Disease 2010 Study. Circulation 2014, 129, 837–847. [Google Scholar] [CrossRef] [Green Version]
  2. Virani, S.S.; Alonso, A.; Benjamin, E.J.; Bittencourt, M.S.; Callaway, C.W.; Carson, A.P.; Chamberlain, A.M.; Chang, A.R.; Cheng, S.; Delling, F.N.; et al. Heart Disease and Stroke Statistics—2020 Update: A Report from the American Heart Association. Circulation 2020, 141, e139–e596. [Google Scholar] [CrossRef] [PubMed]
  3. January, C.T.; Wann, L.S.; Calkins, H.; Chen, L.Y.; Cigarroa, J.E.; Cleveland, J.C., Jr.; Ellinor, P.T.; Ezekowitz, M.D.; Field, M.E.; Furie, K.L.; et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019, 140, e125–e151. [Google Scholar] [CrossRef] [PubMed]
  4. Law, S.W.; Lau, W.; Wong, I.C.; Lip, G.Y.; Mok, M.T.; Siu, C.-W.; Chan, E.W. Sex-Based Differences in Outcomes of Oral Anticoagulation in Patients With Atrial Fibrillation. J. Am. Coll. Cardiol. 2018, 72, 271–282. [Google Scholar] [CrossRef] [PubMed]
  5. Nielsen, P.B.; Skjøth, F.; Overvad, T.F.; Larsen, T.B.; Lip, G.Y.H. Female sex is a risk modifer rather than a risk factor for stroke in atrial fibrillation should we use a CHA 2 DS 2 -VA Score Rather Than CHA 2 DS 2-VASc? Circulation 2018, 137, 832–840. [Google Scholar] [CrossRef]
  6. Hindricks, G.; Potpara, T.; Dagres, N.; Arbelo, E.; Bax, J.J.; Blomström-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). Eur. Heart J. 2020, 42, 373–498. [Google Scholar] [CrossRef]
  7. Essien, U.R.; Magnani, J.W.; Chen, N.; Gellad, W.F.; Fine, M.J.; Hernandez, I. Race/Ethnicity and Sex-Related Differences in Direct Oral Anticoagulant Initiation in Newly Diagnosed Atrial Fibrillation: A Retrospective Study of Medicare Data. J. Natl. Med. Assoc. 2020, 112, 103–108. [Google Scholar] [CrossRef] [PubMed]
  8. Yong, C.M.; Tremmel, J.A.; Lansberg, M.G.; Fan, J.; Askari, M.; Turakhia, M.P. Sex Differences in Oral Anticoagulation and Outcomes of Stroke and Intracranial Bleeding in Newly Diagnosed Atrial Fibrillation. J. Am. Heart Assoc. 2020, 9, e015689. [Google Scholar] [CrossRef]
  9. Thompson, L.E.; Maddox, T.M.; Lei, L.; Grunwald, G.K.; Bradley, S.M.; Peterson, P.N.; Masoudi, F.A.; Turchin, A.; Song, Y.; Doros, G.; et al. Sex Differences in the Use of Oral Anticoagulants for Atrial Fibrillation: A Report From the National Cardiovascular Data Registry (NCDR®) PINNACLE Registry. J. Am. Heart Assoc. 2017, 6, e005801. [Google Scholar] [CrossRef]
  10. Marzona, I.; Proietti, M.; Vannini, T.; Tettamanti, M.; Nobili, A.; Medaglia, M.; Bortolotti, A.; Merlino, L.; Roncaglioni, M.C. Sex-related differences in prevalence, treatment and outcomes in patients with atrial fibrillation. Intern. Emerg. Med. 2020, 15, 231–240. [Google Scholar] [CrossRef]
  11. Mazurek, M.; Huisman, M.V.; Rothman, K.J.; Paquette, M.; Teutsch, C.; Diener, H.-C.; Dubner, S.J.; Halperin, J.L.; Zint, K.; França, L.R.; et al. Gender Differences in Antithrombotic Treatment for Newly Diagnosed Atrial Fibrillation: The GLORIA-AF Registry Program. Am. J. Med. 2018, 131, 945–955. [Google Scholar] [CrossRef] [Green Version]
  12. Li, Y.-M.; Jiang, C.; He, L.; Li, X.-X.; Hou, X.-X.; Chang, S.-S.; Lip, G.Y.; Du, X.; Dong, J.-Z.; Ma, C.-S. Sex Differences in Presentation, Quality of Life, and Treatment in Chinese Atrial Fibrillation Patients: Insights from the China Atrial Fibrillation Registry Study. Med. Sci. Monit. 2019, 25, 8011–8018. [Google Scholar] [CrossRef] [PubMed]
  13. Lip, G.Y.; Laroche, C.; Boriani, G.; Cimaglia, P.; Dan, G.-A.; Santini, M.; Kalarus, Z.; Rasmussen, L.H.; Popescu, M.I.; Tica, O.; et al. Sex-related differences in presentation, treatment, and outcome of patients with atrial fibrillation in Europe: A report from the Euro Observational Research Programme Pilot survey on Atrial Fibrillation. Europace 2014, 17, 24–31. [Google Scholar] [CrossRef] [PubMed]
  14. Diaz, J.; Koza, E.; Chaudhary, D.; Shahjouei, S.; Naved, M.A.; Malik, M.T.; Li, J.; Adibuzzaman, M.; Griffin, P.; Abedi, V.; et al. Adherence to anticoagulant guideline for atrial fibrillation: A large care gap among stroke patients in a rural population. J. Neurol. Sci. 2021, 424, 117410. [Google Scholar] [CrossRef] [PubMed]
  15. Chaudhary, D.; Khan, A.; Shahjouei, S.; Gupta, M.; Lambert, C.; Avula, V.; Schirmer, C.M.; Holland, N.; Griessenauer, C.J.; Azarpazhooh, M.R.; et al. Trends in ischemic stroke outcomes in a rural population in the United States. J. Neurol. Sci. 2021, 422, 117339. [Google Scholar] [CrossRef]
  16. Chaudhary, D.; Khan, A.; Gupta, M.; Hu, Y.; Li, J.; Abedi, V.; Zand, R. Obesity and mortality after the first ischemic stroke: Is obesity paradox real? PLoS ONE 2021, 16, e0246877. [Google Scholar] [CrossRef]
  17. Bhave, P.D.; Lu, X.; Girotra, S.; Kamel, H.; Sarrazin, M.V. Race- and sex-related differences in care for patients newly diagnosed with atrial fibrillation. Heart Rhythm. 2015, 12, 1406–1412. [Google Scholar] [CrossRef] [Green Version]
  18. Xiong, Q.; Shantsila, A.; Lane, D.A.; Zhou, Q.; Liu, Y.; Shen, Y.; Cheng, X.; Hong, K.; Lip, G.Y. Sex differences in clinical characteristics and inpatient outcomes among 2442 hospitalized Chinese patients with nonvalvular atrial fibrillation: The Nanchang Atrial Fibrillation Project. Int. J. Cardiol. 2015, 201, 195–199. [Google Scholar] [CrossRef] [PubMed]
  19. Lip, G.Y.; Rushton-Smith, S.K.; Goldhaber, S.Z.; Fitzmaurice, D.A.; Mantovani, L.G.; Goto, S.; Haas, S.; Bassand, J.-P.; Camm, A.J. Does sex affect anticoagulant use for stroke prevention in nonvalvular atrial fibrillation?: The prospective global anticoagulant registry in the FIELD-Atrial Fibrillation. Circ. Cardiovasc. Qual. Outcomes 2015, 8, S12–S20. [Google Scholar] [CrossRef] [Green Version]
  20. Palareti, G.; Antonucci, E.; Migliaccio, L.; Erba, N.; Marongiu, F.; Pengo, V.; Poli, D.; Testa, S.; Tosetto, A.; Tripodi, A.; et al. Vitamin K antagonist therapy: Changes in the treated populations and in management results in Italian anticoagulation clinics compared with those recorded 20 years ago. Intern. Emerg. Med. 2017, 12, 1109–1119. [Google Scholar] [CrossRef] [Green Version]
  21. Kirchhof, P.; Benussi, S.; Kotecha, D.; Ahlsson, A.; Atar, D.; Casadei, B.; Castella, M.; Diener, H.-C.; Heidbuchel, H.; Hendriks, J.; et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. Heart J. 2016, 37, 2893–2962. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  22. Loikas, D.; Forslund, T.; Wettermark, B.; Schenck-Gustafsson, K.; Hjemdahl, P.; von Euler, M. Sex and Gender Differences in Thromboprophylactic Treatment of Patients with Atrial Fibrillation after the Introduction of Non–Vitamin K Oral Anticoagulants. Am. J. Cardiol. 2017, 120, 1302–1308. [Google Scholar] [CrossRef] [PubMed]
  23. Aronis, K.N.; Thigpen, J.; Tripodis, Y.; Dillon, C.; Forster, K.; Henault, L.; Quinn, E.K.; Berger, P.B.; Limdi, N.A.; Hylek, E.M. Paroxysmal atrial fibrillation and the hazards of under-treatment. Int. J. Cardiol. 2016, 202, 214–220. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Waldo, A.L.; Becker, R.C.; Tapson, V.F.; Colgan, K.J. Hospitalized Patients with Atrial Fibrillation and a High Risk of Stroke Are Not Being Provided With Adequate Anticoagulation. J. Am. Coll. Cardiol. 2005, 46, 1729–1736. [Google Scholar] [CrossRef] [Green Version]
  25. Cohen, N.; Almoznino-Sarafian, D.; Alon, I.; Gorelik, O.; Koopfer, M.; Chachashvily, S.; Shteinshnaider, M.; Litvinjuk, V.; Modai, D. Warfarin for stroke prevention still underused in atrial fibrillation: Patterns of omission. Stroke 2000, 31, 1217–1222. [Google Scholar] [CrossRef] [Green Version]
  26. Liu, T.; Yang, H.-L.; Gu, L.; Huili, Y.; Omorogieva, O.; Ren, M.-X.; Wang, X.-H. Current status and factors influencing oral anticoagulant therapy among patients with non-valvular atrial fibrillation in Jiangsu province, China: A multi-center, cross-sectional study. BMC Cardiovasc. Disord. 2020, 20, 22. [Google Scholar] [CrossRef]
  27. Tulner, L.R.; Van Campen, J.P.C.M.; Kuper, I.M.J.A.; Gijsen, G.J.P.T.; Koks, C.H.W.; Mac Gillavry, M.R.; Van Tinteren, H.; Beijnen, J.H.; Brandjes, D.P.M. Reasons for undertreatment with oral anticoagulants in frail geriatric outpatients with atrial fibrillation: A prospective, descriptive study. Drugs Aging 2010, 27, 39–50. [Google Scholar] [CrossRef]
  28. Lane, D.A.; Lip, G.Y. Use of the CHA 2 DS 2 -VASc and HAS-BLED Scores to Aid Decision Making for Thromboprophylaxis in Nonvalvular Atrial Fibrillation. Circulation 2012, 126, 860–865. [Google Scholar] [CrossRef] [Green Version]
  29. Regpala, S.; Lacombe, S.; Sharma, M.; Gibbens, S.; Ball, D.; Francis, K.; LaHaye, S. Evaluation of patients’ attitudes towards stroke prevention and bleeding risk in atrial fibrillation. Thromb. Haemost. 2014, 111, 465–473. [Google Scholar] [CrossRef]
Jcm 10 04670 g001 550
Figure 1. Flowchart of patients with atrial fibrillation in the study.
Figure 1. Flowchart of patients with atrial fibrillation in the study.
Jcm 10 04670 g001
Jcm 10 04670 g002 550
Figure 2. CHA2DS2-VASc score patient distribution based on sex.
Figure 2. CHA2DS2-VASc score patient distribution based on sex.
Jcm 10 04670 g002
Jcm 10 04670 g003 550
Figure 3. Logistic regression for patients with a CHA2DS2-VASc score ≥ 2 stratified by age groups and index stroke date.
Figure 3. Logistic regression for patients with a CHA2DS2-VASc score ≥ 2 stratified by age groups and index stroke date.
Jcm 10 04670 g003
Table
Table 1. Male and female ischemic stroke patient characteristics with a diagnosis of atrial fibrillation before index stroke event.
Table 1. Male and female ischemic stroke patient characteristics with a diagnosis of atrial fibrillation before index stroke event.
VariableOverallFemaleMalep-Value
Number of patients1062556506
Age at atrial fibrillation diagnosis in years, median (IQR)75.5 (67.3, 82.5)78.9 (69.8, 84.5)72.3 (64.4, 79.2)<0.001 *
Age at index stroke event in years, median (IQR)80.0 (71.5, 86.3)82.6 (74.9, 88.3)76.9 (68.1, 82.9)<0.001 *
CHA2DS2-VASc at baseline, median (IQR)4.0 (3.0, 6.0)5.0 (4.0, 6.0)4.0 (3.0, 5.0)<0.001 *
CHA2DS2-VASc <0.001 *
010 (0.9)0 (0.0)10 (2.0)
137 (3.5)7 (1.3)30 (5.9)
2+1015 (95.6)549 (98.7)466 (92.1)
Dyslipidemia, n (%)740 (69.7)368 (66.2)372 (73.5)0.011 *
Heart failure, n (%)397 (37.4)209 (37.6)188 (37.2)0.934
Hypertension, n (%)900 (84.7)472 (84.9)428 (84.6)0.957
Diabetes, n (%)392 (36.9)188 (33.8)204 (40.3)0.033 *
Past ischemic stroke, n (%)115 (10.8)66 (11.9)49 (9.7)0.295
Transient ischemic attack, n (%)135 (12.7)74 (13.3)61 (12.1)0.603
Other thromboembolism, n (%)79 (7.4)46 (8.3)33 (6.5)0.332
Myocardial infarction, n (%)215 (20.2)84 (15.1)131 (25.9)<0.001 *
Peripheral vascular disease, n (%)275 (25.9)119 (21.4)156 (30.8)0.001 *
Hypercoagulative State, n (%)13 (1.2)9 (1.6)4 (0.8)0.271
Chronic liver disease, n (%)42 (4.0)16 (2.9)26 (5.1)0.084
Cirrhosis, n (%)12 (1.1)6 (1.1)6 (1.2)1.000
Chronic kidney disease, n (%)391 (36.8)217 (39.0)174 (34.4)0.133
End-stage renal disease ESRD, n (%)35 (3.3)13 (2.3)22 (4.3)0.097
Past hemorrhagic stroke, n (%)37 (3.5)18 (3.2)19 (3.8)0.770
Medications
Antiplatelets, n (%)231 (21.8)115 (20.7)116 (22.9)0.418
Anticoagulants, n (%)275 (25.9)146 (26.3)129 (25.5)0.830
Anticoagulant and Antiplatelet, n (%)226 (21.3)106 (19.1)120 (23.7)0.076
Statins, n (%)501 (47.2)242 (43.5)259 (51.2)0.015 *
Antihypertensives, n (%)546 (51.4)272 (48.9)274 (54.2)0.101
Medical insurance type, n (%) † <0.001 *
Commercial132 (12.8)55 (10.2)77 (15.7)
Health Maintenance Organization (HMO)352 (34.1)174 (32.2)178 (36.2)
Medicaid13 (1.3)7 (1.3)6 (1.2)
Medicare518 (50.2)297 (55.0)221 (44.9)
Self-Pay1 (0.1)1 (0.2)0 (0.0)
Special Billing9 (0.9)6 (1.1)3 (0.6)
Veterans Affairs (VA)7 (0.7)0 (0.0)7 (1.4)
Smoking status, n (%) <0.001 *
Current smoke87 (8.2)25 (4.5)62 (12.3)
Past smoker408 (38.4)140 (25.2)268 (53.0)
Never smoker520 (49.0)368 (66.2)152 (30.0)
Unknown47 (4.4)23 (4.1)24 (4.7)
NIHSS at index stroke event, median (IQR) #5.0 (2.0, 9.0)6.0 (3.0, 12.0)4.0 (2.0, 6.0)0.001 *
All-cause mortality within 1 year of index stroke, n (%)303 (28.5)164 (29.5)139 (27.5)0.508
Recorded encounter count per year between diagnosis of atrial fibrillation and index stroke, median (IQR)6.3 (3.0, 11.0)6.9 (3.0, 11.0)6.0(3.0, 10.8)0.404
Time in years between diagnosis of atrial fibrillation and index stroke, median (IQR)2.8 (1.0, 5.6)2.9 (1.0, 5.5)2.6 (1.0, 5.6)0.899
* Significant p-value; † Medical insurance data available for 1032 patients (540 female and 492 male patients); # NIHSS available for only 261 patients (136 female and 125 male patients).
Table
Table 2. Anticoagulant undertreatment rates for patients with a CHA2DS2-VASc score ≥ 2 stratified by age groups and index stroke date.
Table 2. Anticoagulant undertreatment rates for patients with a CHA2DS2-VASc score ≥ 2 stratified by age groups and index stroke date.
All PatientsUndertreated
TotalFemaleMale Total Female Male p-Value
All Groups1015549466532
(52.4%)		299
(54.5%)		233
(50.0%)		0.175
Stratified by AgeGroup 1 (44.4–72.8 years)254110144141
(55.5%)		64
(58.2%)		77
(53.5%)		0.535
Group 2 (72.8–80.6 years)254112142120
(47.2%)		59
(52.7%)		61
(43.0%)		0.157
Group 3 (80.6–86.6 years)254138116122
(48.0%)		64
(46.4%)		58
(50.0%)		0.653
Group 4 (>86.6 years)25318964149
(58.9%)		112
(59.3%)		37
(57.8%)		0.955
Stratified by Index Date2004–2010221108113112
(50.7%)		54
(50.0%)		58
(51.3%)		0.950
2011–2019794441353420
(52.9%)		245
(55.6%)		175
(49.6%)		0.108
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Koza, E.; Diaz, J.; Chaudhary, D.; Shahjouei, S.; Li, J.; Abedi, V.; Zand, R. Lack of Sex Disparity in Oral Anticoagulation in Atrial Fibrillation Patients Presenting with Ischemic Stroke in a Rural Population. J. Clin. Med. 2021, 10, 4670. https://doi.org/10.3390/jcm10204670

AMA Style

Koza E, Diaz J, Chaudhary D, Shahjouei S, Li J, Abedi V, Zand R. Lack of Sex Disparity in Oral Anticoagulation in Atrial Fibrillation Patients Presenting with Ischemic Stroke in a Rural Population. Journal of Clinical Medicine. 2021; 10(20):4670. https://doi.org/10.3390/jcm10204670

Chicago/Turabian Style

Koza, Eric, Johan Diaz, Durgesh Chaudhary, Shima Shahjouei, Jiang Li, Vida Abedi, and Ramin Zand. 2021. "Lack of Sex Disparity in Oral Anticoagulation in Atrial Fibrillation Patients Presenting with Ischemic Stroke in a Rural Population" Journal of Clinical Medicine 10, no. 20: 4670. https://doi.org/10.3390/jcm10204670

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