Journal List > J Stroke > v.25(1) > 1516081112

TOOLS
Shu, Havenon, Liberman, Henninger, Goldstein, Reznik, Mahta, Al-Mufti, Frontera, Furie, and Yaghi: Trends in Venous Thromboembolism Readmission Rates after Ischemic Stroke and Intracerebral Hemorrhage
Original Article

J Stroke 2023;25(1):151-159.

Published online: 3 January 2023

DOI: https://doi.org/10.5853/jos.2022.02215

Trends in Venous Thromboembolism Readmission Rates after Ischemic Stroke and Intracerebral Hemorrhage

Liqi Shua, Adam de Havenonb, Ava L. Libermanc, Nils Henningerd, e, Eric Goldsteina, Michael E. Reznika, Ali Mahtaa, Fawaz Al-Muftif, g, Jennifer Fronterah, Karen Furiea, Shadi Yaghia

aDepartment of Neurology, Brown University, Providence, RI, USA

bDepartment of Neurology, Yale University, New Haven, CT, USA

cDepartment of Neurology, Weill Cornell Medical Center, New York, NY, USA

dDepartment of Neurology, University of Massachusetts, Worcester, MA, USA

eDepartment of Psychiatry, University of Massachusetts, Worcester, MA, USA

fDepartment of Neurology, Westchester Medical Center, Valhalla, NY, USA

gDepartment of Neurosurgery, Westchester Medical Center, Valhalla, NY, USA

hDepartment of Neurology, New York University, New York, NY, USA

Correspondence: Shadi Yaghi Department of Neurology, Brown Medical School, 593 Eddy Street APC 5, Providence, RI, 02903, USA Tel: +1-401-444-8806 Fax: +1-401-444-8781 E-mail: shadiyaghi@yahoo.com

Received 8 July 2022       Revised 3 September 2022       Accepted 8 September 2022

Copyright © 2023 Korean Stroke Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background and Purpose

Venous thromboembolism (VTE) is a life-threatening complication of stroke. We evaluated nationwide rates and risk factors for hospital readmissions with VTE after an intracerebral hemorrhage (ICH) or acute ischemic stroke (AIS) hospitalization.

Methods

Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included patients with a principal discharge diagnosis of ICH or AIS from 2016 to 2019. Patients who had VTE diagnosis or history of VTE during the index admission were excluded. We performed Cox regression models to determine factors associated with VTE readmission, compared rates between AIS and ICH and developed post-stroke VTE risk score. We estimated VTE readmission rates per day over a 90-day time window post-discharge using linear splines.

Results

Of the total 1,459,865 patients with stroke, readmission with VTE as the principal diagnosis within 90 days occurred in 0.26% (3,407/1,330,584) AIS and 0.65% (843/129,281) ICH patients. The rate of VTE readmission decreased within first 4–6 weeks (P<0.001). In AIS, cancer, obesity, higher National Institutes of Health Stroke Scale (NIHSS) score, longer hospital stay, home or rehabilitation disposition, and absence of atrial fibrillation were associated with VTE readmission. In ICH, longer hospital stay and rehabilitation disposition were associated with VTE readmission. The VTE rate was higher in ICH compared to AIS (adjusted hazard ratio 2.86, 95% confidence interval 1.93–4.25, P<0.001).

Conclusions

After stroke, VTE readmission risk is highest within the first 4–6 weeks and nearly three-fold higher after ICH vs. AIS. VTE risk is linked to decreased mobility and hypercoagulability. Studies are needed to test short-term VTE prophylaxis beyond hospitalization in high-risk patients.

Keywords: Acute stroke, Deep venous thrombosis, Venous thromboembolism, Pulmonary embolism

Introduction

Stroke is a leading cause of mortality and morbidity [1]. Advancements in acute stroke treatments and improved inpatient stroke care have led to decreased stroke-related mortality, but patients remain at risk for secondary complications [2].
Despite current preventative strategies, clinically evident venous thromboembolism (VTE) is an important post-stroke complication that occurs in up to 5% of immobile stroke patients within the first 30-days [3] and contributes to post-stroke mortality [4]. Therefore, understanding factors associated with such complications is of paramount importance to identify patients at risk and ultimately improve therapeutic measures to reduce VTE-associated morbidity and mortality after stroke.
While current treatments such as mechanical or chemical VTE prophylaxis, are generally utilized in hospitalized stroke patients [5], quality efforts do not generally oversee the use of such measures in the post-hospitalization phase, i.e., acute rehabilitation units and skilled nursing facilities. Furthermore, in patients with high risk of major bleeding such as patients with intracerebral hemorrhage (ICH), chemical prophylaxis is considered based on risk of VTE [6], and may be avoided or delayed [7]. Therefore, it is crucial to identify patients at high-risk for VTE after their initial stroke hospitalization who may benefit from continued VTE prophylactic measures beyond their initial inpatient hospital stay. In this study, we aim to determine predictors of VTE readmissions in both hemorrhagic and ischemic stroke patients and compare VTE risk in patients with ICH to those with acute ischemic stroke (AIS).

Methods

IRB approval was waived by Lifespan Institutional Review Board since our analysis used de-identified publicly available data. Informed consent was waived by the IRB as the dataset used is a publicly available de-identified. The Nationwide Readmissions Database (NRD) used for this analysis is publicly available through the Healthcare Cost and Utilization Project (HCUP) at https://www.hcup-us.ahrq.gov/.

Patient population

We included adult patients 18 years or older hospitalized with a principal diagnosis of AIS or non-traumatic ICH using the HCUP Nationwide Database between January 1st, 2016 and December 31st, 2019. Diagnoses were identified based on ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) codes (Supplementary Table 1). For stroke, when used as a primary diagnosis, ICD-10 code has a positive predictive value of 99.8% and a sensitivity of 87.2% [8]. We excluded patients with a new VTE diagnosis at the time of index stroke admission, a prior history of VTE, and patients who died during the index admission. Due to the inability of following patients across different years, patients who were discharged from October to December were excluded each year to allow a follow-up duration of 90 days. Since we are interested in the short-term risk of a VTE readmission in stroke patients, we also excluded patients whose index admission exceeded 30 days in duration (Figure 1).

Predictors

The variables of interest were abstracted from the list of diagnoses during the index hospitalization. These included:

  • (1) Demographic variables: age, sex, insurance status (Medicaid, Medicare, private insurance, and self-pay), median income by zip code (divided into quartiles according to HCUP thresholds), and hospital type (metropolitan teaching, metropolitan non-teaching, non-metropolitan).

  • (2) Clinical variables: history of hypertension, diabetes, cancer, congestive heart failure, obesity, and peripheral vascular disease generated with Elixhauser Comorbidity Software (Version 3.7), available on the HCUP website. History of coronary artery disease, history of atrial fibrillation or atrial flutter, National Institutes of Health Stroke Scale (NIHSS) score (continuous variable), hospital length of stay (continuous variable), and discharge disposition.

  • (3) In-hospital treatments: intravenous thrombolytics and mechanical thrombectomy.

Outcomes

The primary outcome was a hospital readmission within 90-days with a principal diagnosis of VTE. ICD-10 codes of pulmonary embolism and deep vein thrombosis (DVT) hospitalization were shown to have a good positive predictive value (87%) [9]. We did not consider non-principal VTE readmission in the VTE outcome since VTEs occurring during a readmission could possibly be secondary to other etiologies.

Analytical plan

Patients were divided into two groups based on the occurrence of primary outcome. We compared baseline characteristics between the two weighted groups using univariate logistic regression. We identified variables with P<0.1 from the univariate analysis and included them in weighted Cox regression analyses to determine potentially relevant predictors of the primary outcome.
We also performed weighted Cox regression with unadjusted and adjusted propensity score weighting [10] to compare the risk of VTE readmission in ICH compared to AIS. We adopted propensity score methods in combination with survey weighting in order to obtain unbiased treatment effect estimates [10]. Two different methods were used to estimate the propensity score weight. The first “propensity score matching” method utilized nearest neighbor one-to-one propensity score matching, where the matched weight was derived by multiplying the survey weights with the propensity score weights. Alternatively, the second “propensity weighted analysis” method was similar to the inverse probability of treatment weighting. Patients were re-weighted using the matched weight, which was derived by multiplying the survey weights with the doubly robust estimation weights [11]. For adjustment and weighting, we included all variables associated with VTE readmissions in Cox regression models in patients with AIS and ICH. For Cox regression models, proportionality was assessed using Schoenfeld’s residuals and parametric survival models were used when proportionality was not met.
Kaplan-Meier survival estimates were performed in both groups. Furthermore, to determine the risk of VTE over time, VTE readmission rates per day over 90-day were estimated with linear splines and the breakpoint was identified by joinpoint regression.
Finally, a risk scoring system for post-stroke VTE was developed with nomogram, which was generated using risk factors identified in Cox regression (Supplementary Table 2). NIHSS and the length of stay were dichotomized using the Youden Index cut-point. Area under the curve (AUC) was used to assess predictive accuracy. We then categorized patients into different risk groups and compared their absolute risk of post-stroke VTE readmission. All analyses were performed using Stata version 15 (StataCorp., College Station, TX, USA) and P<0.05 was considered statistically significant.

Results

Study cohort and overall VTE rates

Of the 2,288,058 patients with AIS or ICH as their principal diagnosis in their index admission, 1,459,865 met the inclusion criteria (Figure 1 depicts the study flow chart). Among the 1,330,584 included AIS patients, the mean age was 70.0±0.1 years, 49.6% (660,175/1,330,584) were women, and 3,407 (0.26%) had VTE as the principal diagnosis for readmission within 90 days of initial hospital discharge. Among the 129,281 included ICH patients, the mean age was 68.5±0.1 years, 47.9% (61,967/129,281) were women, and 0.65% (843) had VTE as the principal diagnosis for a readmission within 90 days of initial hospital discharge. The VTE readmission rate per day declined over the 90-day period and the trend significantly decelerated after day 30 for AIS patients (P<0.001) and day 46 for ICH patients (P<0.001) (Figure 2).

Factors associated with VTE readmission on univariate analyses in AIS

In univariate analyses, when compared to AIS patients without a VTE readmission, those with a VTE readmission were more likely to be older (71.1±0.3 years vs. 70.0±0.1 years, P=0.002), women (54.6% vs. 49.6%, P<0.001), have a cancer diagnosis (10.8% vs. 4.0%, P<0.001), have congestive heart failure (17.6% vs. 15.5%, P=0.020), obesity (18.3% vs. 14.0%, P<0.001), have a higher NIHSS score (median [interquartile range, IQR]: 6 [3–14] vs. 4 [1–8], P<0.001), have Medicare insurance (71.7% vs. 66.7%, P<0.001), be treated at a metropolitan teaching hospital (73.1% vs. 70.6%, P=0.027), receive intravenous thrombolysis (11.2% vs. 9.4%, P=0.020), mechanical thrombectomy (5.8% vs. 3.5%, P<0.001), have a longer length of stay (median [IQR]: 5 days [3–8] vs. 3 days [2–6], P<0.001), and be discharged to a rehabilitation or skilled nursing facility (56.6% vs. 34.9%, P<0.001), and less likely to have atrial fibrillation or flutter (19.9% vs. 24.2%, P<0.001). Other characteristics were not significantly different between the two groups (Table 1).

Factors associated with VTE readmission in univariate analyses in ICH

In univariate analyses, when compared to ICH patients without a VTE readmission, those with a VTE readmission were more likely to have atrial fibrillation (24.7% vs. 20.3%, P=0.048), have obesity (20.4% vs. 11.6%, P<0.001), have a higher median NIHSS score (median [IQR]: 10 [4–16] vs. 5 [2–13], P=0.001), have longer length of stay (median [IQR]: 8 days [4–14] vs. 5 days [3–11], P<0.001), and be discharged to a rehabilitation or skilled nursing facility (73.2% vs. 50.2%, P<0.001). On the contrary, VTE readmission was less common in patients in the 2nd quartile of the estimated median household income zip code (22.0% vs. 26.6%, P=0.043), home discharge (13.8% vs. 30.3%, P<0.001) or home with services discharge (10.8% vs. 16.2%, P=0.004). Other characteristics were not significantly different between the two groups (Table 1).

Factors associated with VTE readmission in AIS and ICH in Cox regression models

In Cox regression models, factors associated with increased rates of VTE readmission in patients with AIS were cancer (adjusted hazard ratios [aHR] 2.17, 95% confidence interval [CI] 1.63–2.90, P<0.001), obesity (aHR 1.73, 95% CI 1.42–2.10, P<0.001), higher NIHSS score (aHR 1.03 per point, 95% CI 1.02–1.04, P<0.001), longer hospital length of stay (aHR 1.03 per day, 95% CI 1.02–1.04, P<0.001), and disposition to home with services (aHR 1.60, 95% CI 1.22–2.11, P=0.001) or rehabilitation or nursing home (aHR 2.74, 95% CI 2.18–3.44, P<0.001) as opposed to disposition to home without services. On the other hand, atrial fibrillation was associated with a lower VTE readmission risk (aHR 0.57, 95% CI 0.45–0.71, P<0.001) (Table 2).
In ICH patients, factors significantly associated with increased rates of VTE readmission were longer hospital length of stay (aHR 1.04 per day, 95% CI 1.01–1.06, P=0.005) and disposition to rehabilitation or nursing home (aHR 2.77, 95% CI 1.34–5.76, P=0.006) (Table 2).

Comparing VTE readmission risk between AIS and ICH

In the unadjusted analysis, when compared to AIS, ICH conferred a higher risk of VTE readmission (HR 2.56, 95% CI 2.28–2.87, P<0.001) (Figure 3). This finding persisted after adjusting for potential confounders (aHR 2.10, 95% CI 1.67–2.65, P<0.001), propensity score matching (aHR 1.89, 95% CI 1.34–2.66, P<0.001), and propensity weighted adjusted analyses (aHR 2.86, 95% CI 1.93–4.25, P<0.001) (Table 3).

Post-stroke VTE risk score

Derived from the nomogram, the post-stroke VTE risk score (AUC: 0.70 [0.68–0.72]) used total 7 factors: ICH during index event, cancer, no history of atrial fibrillation, obesity, higher NIHSS (>4 points), longer length of stay (>3 days), and disposition to home with services, rehabilitation or nursing home. For those patients in the low (0–14), medium (15–34), and high risk (35–45) categories, the VTE readmission rates were 1,625/951,656 (0.2%), 2,617/ 507,868 (0.5%), and 8/343 (2.3%), respectively (P<0.001).

Discussion

In this nationwide analysis of post-stroke patients, we found that the 90-day risk of VTE readmission is associated with factors linked to immobility and hypercoagulability. Furthermore, the risk of VTE readmission was highest in the first 30 days in AIS and 46 days in ICH and significantly decreased thereafter.
Some of our findings differed from prior studies. For instance, atrial fibrillation was shown to be associated with VTE after ischemic stroke in prior studies [12,13]. In our study atrial fibrillation was associated with lower risk of post-stroke VTE. The prior studies were conducted in the early 1990s when only 1.5% of their patients were treated with anticoagulation [13]. In current practice, these rates are substantially higher, particularly with anticoagulation by discharge being a joint commission quality measure in AIS patients with atrial fibrillation. Therefore, early initiation of oral anticoagulation in patients with atrial fibrillation according to current joint commission quality measures may be an important driver of reduced VTE risk in such patients. This notion is further supported by our observation that atrial fibrillation was not independently associated with VTE readmission risk after ICH, presumably because in such patients, initiation of oral anticoagulation may be delayed or considered contraindicated depending on the ICH etiology. Which again implies that the lower risk of VTE in atrial fibrillation patients may be due to anticoagulation therapy. Furthermore, the association between cancer and VTE risk in stroke patients is in line with studies suggesting the occurrence of hypercoagulability in the setting of cancer [14,15], which increases the risk of VTE [16]. Moreover, many risk factors for VTE readmission in our study have previously been linked to impaired mobility, such as increased hospital length of stay, stroke severity, discharge to a rehabilitation or skilled nursing facility, and obesity [17-20]. That said, there may be surveillance bias for facility disposition where VTE patients may more likely be sent to the hospital, and this finding should be interpreted with caution. Several studies have investigated extended VTE prophylaxis use in acutely ill medical patients and demonstrated decreased rate of VTE at a cost of increased rate of major bleeding. Stroke patients may have different coagulopathy (inherent disease or medication) and immobility than acutely ill medical patients. Further studies in this special subgroup patients are needed to test interventions such as early mobilization of stroke patients [21], reducing the length of hospital stay to reduce the VTE rates, shortterm use of mechanical and/or chemical DVT prophylaxis after hospital discharge, particularly in high-risk patients. Furthermore, standard doses of chemical prophylactic agents may not be as effective in obese patients [19,22].
Similar to prior studies [23,24], our study also showed that the risk of VTE was three-fold higher in ICH patients when compared to those with AIS. One possible explanation is the lower rates and delay in initiation of chemical VTE prophylaxis in ICH compared to AIS. Despite guidelines recommending chemical prophylaxis to be initiated between 1 and 4 days after ICH onset provided cessation of active bleeding [7], one study showed that less than 20% of patients with ICH received chemical VTE prophylaxis, of whom less than half of them received it within 2 days after ICH onset [24]. Patients with ICH are also more likely to require an intensive care unit admission, have higher morbidity, and have a longer length of hospital stay than patients with AIS, all of which may contribute to the higher risk of VTE in patients with ICH compared to those with AIS. Nevertheless, our findings suggesting higher rates of VTE in ICH patients persisted even after adjusting for these factors.
Finally, we found that rates of VTE are highest during the first 30 days after ischemic stroke and 46 days from ICH, which is consistent with prior studies [25,26]. This is in line with findings from prior studies showing the risk of VTE in stroke patients extends into the acute rehabilitation phase [12,27]. Thus studies are needed to investigate the efficacy and safety of continued mechanical and chemical prophylaxis beyond the hospital setting in high-risk patients and up to these time points with AIS and ICH. Furthermore, given the risk of VTE is significantly lower beyond these time points, long-term chemical or mechanical prophylaxis may not be beneficial and is not recommended by clinical guidelines [28].
There are several limitations to our study. Although this national database allows analysis of a very large number of patients, it lacks specific patient-level data. For example, despite accounting for multiple comorbidities, certain clinically relevant measures such as the use of anticoagulation and intermittent pneumatic compression are not available in this dataset. The national readmission database only provides disposition in limited categories, and it combines acute rehabilitation and skilled nursing facilities into one category. This is particularly important as patients who were discharged to long-term care have the most disability and the least potential for a good recovery than those discharged to acute rehabilitation. That said, the general criteria for discharge to acute rehabilitation are being unable to walk independently even with the use of an assistive device, which would imply a modified Rankin Scale score of 4 or 5 and thus have decreased mobility and are still at risk for VTE.
Importantly, we only considered patients who were hospitalized with VTE, and thus VTEs diagnosed and treated in the outpatient setting were not included. The rate of post-stroke VTE was reported to be up to 17% for asymptomatic and symptomatic patients and about 1% for clinically relevant events in prior studies [29,30]. Furthermore, patients with sudden death from an undiagnosed pulmonary embolus were also not included. These factors may have contributed to a lower rate of VTE in our study compared to prior studies [3]. Another limitation of our study is the exclusion of patients hospitalized between October and December. We however do not expect the variables and findings used in this study to vary based on this exclusion.

Conclusion

Although patients with stroke have a low rate of readmission for VTE, ICH and factors related to decreased mobility and/or hypercoagulability can put them at a higher risk of VTE. Further studies are needed to determine whether early mobilization and mechanical and/or short-term chemical prophylaxis post-discharge reduce the risk in high-risk patients.

Supplementary materials

Supplementary materials related to this article can be found online at https://doi.org/10.5853/jos.2022.02215.
Supplementary Table 1.
Diagnoses based on International Classification of Diseases, Tenth Revision (ICD-10) code
jos-2022-02215-Supplementary-Table.pdf
Supplementary Table 2.
Post-stroke venous thromboembolism score
jos-2022-02215-Supplementary-Table.pdf

Notes

Disclosure

The authors have no financial conflicts of interest.

ACKNOWLEDGMENTS

None

References

1. Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, et al. Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation. 2021; 143:e254–e743.
2. Seminog OO, Scarborough P, Wright FL, Rayner M, Goldacre MJ. Determinants of the decline in mortality from acute stroke in England: linked national database study of 795869 adults. BMJ. 2019; 365:l1778.
3. Dennis M, Mordi N, Graham C, Sandercock P; CLOTS trials collaboration. The timing, extent, progression and regression of deep vein thrombosis in immobile stroke patients: observational data from the CLOTS multicenter randomized trials. J Thromb Haemost. 2011; 9:2193–2200.
4. Viitanen M, Winblad B, Asplund K. Autopsy-verified causes of death after stroke. Acta Med Scand. 1987; 222:401–408.
5. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019; 50:e344–e418.
6. Anderson DR, Morgano GP, Bennett C, Dentali F, Francis CW, Garcia DA, et al. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients. Blood Adv. 2019; 3:3898–3944.
7. Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke. 2015; 46:2032–2060.
8. Hsieh MT, Hsieh CY, Tsai TT, Wang YC, Sung SF. Performance of ICD-10-CM diagnosis codes for identifying acute ischemic stroke in a national health insurance claims database. Clin Epidemiol. 2020; 12:1007–1013.
9. Molander V, Bower H, Askling J. Validation and characterization of venous thromboembolism diagnoses in the Swedish National Patient Register among patients with rheumatoid arthritis. Scand J Rheumatol. 2022; Jan. 13. [Epub]. https://doi.org/10.1080/03009742.2021.2001907.
10. Dugoff EH, Schuler M, Stuart EA. Generalizing observational study results: applying propensity score methods to complex surveys. Health Serv Res. 2014; 49:284–303.
11. Garrido MM, Kelley AS, Paris J, Roza K, Meier DE, Morrison RS, et al. Methods for constructing and assessing propensity scores. Health Serv Res. 2014; 49:1701–1720.
12. Kelly J, Rudd A, Lewis R, Hunt BJ. Venous thromboembolism after acute stroke. Stroke. 2001; 32:262–267.
13. Noel P, Gregoire F, Capon A, Lehert P. Atrial fibrillation as a risk factor for deep venous thrombosis and pulmonary emboli in stroke patients. Stroke. 1991; 22:760–762.
14. Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood. 2013; 122:1712–1723.
15. Caine GJ, Stonelake PS, Lip GY, Kehoe ST. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia. 2002; 4:465–473.
16. Stein PD, Beemath A, Meyers FA, Skaf E, Sanchez J, Olson RE. Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med. 2006; 119:60–68.
17. Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med. 2005; 118:978–980.
18. Eichinger S, Hron G, Bialonczyk C, Hirschl M, Minar E, Wagner O, et al. Overweight, obesity, and the risk of recurrent venous thromboembolism. Arch Intern Med. 2008; 168:1678–1683.
19. Henke PK, Kahn SR, Pannucci CJ, Secemksy EA, Evans NS, Khorana AA, et al. Call to action to prevent venous thromboembolism in hospitalized patients: a policy statement from the American Heart Association. Circulation. 2020; 141:e914–e931.
20. Amin A, Neuman WR, Lingohr-Smith M, Menges B, Lin J. Influence of the duration of hospital length of stay on frequency of prophylaxis and risk for venous thromboembolism among patients hospitalized for acute medical illnesses in the USA. Drugs Context. 2019; 8:212568.
21. Silver B, Hamid T, Khan M, Di Napoli M, Behrouz R, Saposnik G, et al. 12 versus 24 h bed rest after acute ischemic stroke thrombolysis: a preliminary experience. J Neurol Sci. 2020; 409:116618.
22. Nutescu EA, Spinler SA, Wittkowsky A, Dager WE. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother. 2009; 43:1064–1083.
23. Gregory PC, Kuhlemeier KV. Prevalence of venous thromboembolism in acute hemorrhagic and thromboembolic stroke. Am J Phys Med Rehabil. 2003; 82:364–369.
24. Prabhakaran S, Herbers P, Khoury J, Adeoye O, Khatri P, Ferioli S, et al. Is prophylactic anticoagulation for deep venous thrombosis common practice after intracerebral hemorrhage? Stroke. 2015; 46:369–375.
25. Rinde LB, Småbrekke B, Mathiesen EB, Løchen ML, Njølstad I, Hald EM, et al. Ischemic stroke and risk of venous thromboembolism in the general population: the Tromsø study. J Am Heart Assoc. 2016; 5:e004311.
26. Dennis M, Mordi N, Graham C, Sandercock P; CLOTS trials collaboration. The timing, extent, progression and regression of deep vein thrombosis in immobile stroke patients: observational data from the CLOTS multicenter randomized trials. J Thromb Haemost. 2011; 9:2193–2200.
27. Subbarao J, Smith J. Pulmonary embolism during stroke rehabilitation. IMJ Ill Med J. 1984; 165:328–332.
28. Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e195S–e226S.
29. Kamphuisen PW, Agnelli G. What is the optimal pharmacological prophylaxis for the prevention of deep-vein thrombosis and pulmonary embolism in patients with acute ischemic stroke? Thromb Res. 2007; 119:265–274.
30. Skaf E, Stein PD, Beemath A, Sanchez J, Bustamante MA, Olson RE. Venous thromboembolism in patients with ischemic and hemorrhagic stroke. Am J Cardiol. 2005; 96:1731–1733.

Figure 1.
Flow chart of the study. AIS, acute ischemic stroke; ICH, intracerebral hemorrhage; VTE, venous thromboembolism. *Patients may have more than one exclusion reason.
jos-2022-02215f1.tif
Figure 2.
Trends in venous thromboembolism readmissions in (A) acute ischemic stroke (AIS) and (B) intracerebral hemorrhage (ICH) over 90 days.
jos-2022-02215f2.tif
Figure 3.
Kaplan-Meier survival estimates of venous thromboembolism readmission in acute ischemic stroke (AIS) vs. intracerebral hemorrhage (ICH).
jos-2022-02215f3.tif
Table 1.
Baseline characteristics across patients with vs. without VTE readmission in AIS and ICH
Variable AIS
 ICH
VTE readmission (n=3,407) No VTE readmission (n=1,327,177) P VTE readmission (n=843) No VTE readmission (n=128,438) P
Age (yr) 71.1±0.3 70.0±0.1 0.002 69.5±0.7 68.5±0.1 0.187
Female sex 1,861/3,407 (54.6) 658,313/1,327,177 (49.6) <0.001 436/843 (51.7) 61,531/128,438 (47.9) 0.140
Insurance
  Private insurance 503/3,404 (14.8) 239,487/1,325,252 (18.1) 0.001 161/841 (19.1) 25,000/128,210 (19.5) 0.872
Medicare 2,439/3,404 (71.7) 883,509/1,325,252 (66.7) <0.001 576/841 (68.5) 80,725/128,210 (63.0) 0.028
Medicaid 293/3,404 (8.6) 117,642/1,325,252 (8.9) 0.708 67/841 (8.0) 13,811/128,210 (10.8) 0.152
Self-pay 169/3,404 (5.0) 84,614/1,325,252 (6.4) 0.023 37/841 (4.4) 8,674/128,210 (6.8) 0.057
Household income
Zip income 1st quartile 1,097/3,363 (32.6) 407,405/1,309,721 (31.1) 0.203 229/828 (27.7) 37,027/126,804 (29.2) 0.530
Zip income 2nd quartile 890/3,363 (26.5) 357,907/1,309,721 (27.3) 0.476 182/828 (22.0) 33,722/126,804 (26.6) 0.043
Zip income 3rd quartile 788/3,363 (23.4) 312,421/1,309,721 (23.9) 0.682 240/828 (29.0) 30,800/126,804 (24.3) 0.051
Zip income 4th quartile 588/3,363 (17.5) 231,988/1,309,721 (17.7) 0.811 177/828 (21.4) 25,255/126,804 (19.9) 0.488
Hospital type
Metropolitan non-teaching 710/3,407 (20.8) 283,763/1,327,177 (21.4) 0.589 109/843 (12.9) 17,173/128,438 (13.4) 0.785
Metropolitan teaching 2,491/3,407 (73.1) 936,359/1,327,177 (70.6) 0.027 723/843 (85.8) 107,773/128,438 (83.9) 0.302
Non-metropolitan hospital 206/3,407 (6.0) 107,055/1,327,177 (8.1) 0.005 11/843 (1.3) 3,492/128,438 (2.7) 0.194
Hypertension 2,928/3,407 (85.9) 1,142,372/1,327,177 (86.1) 0.874 738/843 (87.5) 111,794/128,438 (87.0) 0.776
Diabetes 1,275/3,407 (37.4) 517,927/1,327,177 (39.0) 0.200 245/843 (29.1) 36,838/128,438 (28.7) 0.890
Coronary artery disease 957/3,407 (28.1) 355,676/1,327,177 (26.8) 0.288 181/843 (21.5) 25,620/128,438 (19.9) 0.465
Cancer 367/3,407 (10.8) 52,584/1,327,177 (4.0) <0.001 82/843 (9.7) 7,726/128,438 (6.0) <0.001
Congestive heart failure 598/3,407 (17.6) 205,231/1,327,177 (15.5) 0.020 102/843 (12.1) 15,046/128,438 (11.7) 0.837
Peripheral vascular disease 350/3,407 (10.3) 137,762/1,327,177 (10.4) 0.909 53/843 (6.3) 8,868/128,438 (6.9) 0.653
Atrial fibrillation or flutter 679/3,407 (19.9) 321,784/1,327,177 (24.2) <0.001 208/843 (24.7) 26,021/128,438 (20.3) 0.048
Obesity 624/3,407 (18.3) 186,417/1,327,177 (14.0) <0.001 172/843 (20.4) 14,943/128,438 (11.6) <0.001
NIHSS 6 [3–14] 4 [1–8] <0.001 10 [4–16] 5 [2–13] 0.001
NIHSS ≥10 475/1,218 (39.0) 87,414/435,424 (20.1) <0.001 100/188 (53.2) 7,660/22,244 (34.4) <0.001
IV thrombolytics 380/3,407 (11.2) 125,168/1,327,177 (9.4) 0.020
Thrombectomy 196/3,407 (5.8) 45,915/1,327,177 (3.5) <0.001
Length of stay (day) 5 [3–8] 3 [2–6] <0.001 8 [4–14] 5 [3–11] <0.001
Length of stay >7 days 1,002/3,407 (29.4) 232,586/1,327,177 (17.5) <0.001 449/843 (53.3) 46,548/128,438 (36.2) <0.001
Discharge disposition
Home without services 806/3,407 (23.7) 578,363/1,327,090 (43.6) <0.001 116/843 (13.8) 38,954/128,432 (30.3) <0.001
Home with services 581/3,407 (17.1) 250,927/1,327,090 (18.9) 0.053 92/843 (10.8) 20,840/128,432 (16.2) 0.004
Rehab or nursing home 1,927/3,407 (56.6) 463,394/1,327,090 (34.9) <0.001 617/843 (73.2) 64,444/128,432 (50.2) <0.001
Other 93/3,407 (2.7) 34,406/1,327,090 (2.6) 0.708 18/843 (2.3) 4,194/128,432 (3.3) 0.246

Data are presented as mean±standard deviation, number (percentage), or median [interquartile range]. Percentages may not total 100% due to rounding.

VTE, venous thromboembolism; AIS, acute ischemic stroke; ICH, intracerebral hemorrhage; NIHSS, National Institutes of Health Stroke Scale; IV, intravenous.

Table 2.
Variables associated with venous thromboembolism readmission in AIS and ICH patients in Cox regression analysis
Variable AIS (n=435,906)
 ICH (n=22,096)
Adjusted hazard ratio 95% confidence interval P>|t| Adjusted hazard ratio 95% confidence interval P>|t|
Age 1.01 1.00–1.02 0.143 NA NA NA
Female sex 1.09 0.93–1.27 0.304 NA NA NA
Insurance
  Private insurance Ref Ref Ref Ref Ref Ref
Medicare 0.86 0.67–1.11 0.241 1.16 0.67–1.99 0.596
Medicaid 0.95 0.66–1.35 0.758 0.41 0.15–1.10 0.075
Self-pay 1.14 0.77–1.68 0.518 1.12 0.39–3.24 0.828
Household income
Zip income 1st quartile NA NA NA Ref Ref Ref
Zip income 2nd quartile NA NA NA 1.12 0.62–2.02 0.719
Zip income 3rd quartile NA NA NA 1.39 0.77–2.51 0.278
Zip income 4th quartile NA NA NA 0.92 0.49–1.70 0.781
Hospital type
Metropolitan non-teaching Ref Ref Ref NA NA NA
Metropolitan teaching 1.03 0.83–1.28 0.775 NA NA NA
Non-metropolitan hospital 0.80 0.49–1.30 0.358 NA NA NA
Cancer 2.17 1.63–2.90 <0.001 1.76 0.69–4.50 0.236
Congestive heart failure 1.05 0.84–1.31 0.679 NA NA NA
Atrial fibrillation or flutter 0.57 0.45–0.71 <0.001 1.40 0.87–2.28 0.169
Obesity 1.73 1.42–2.10 <0.001 1.61 0.96–2.70 0.072
NIHSS score 1.03 1.02–1.04 <0.001 1.01 0.99–1.03 0.367
IV thrombolytics 1.04 0.82–1.31 0.758 NA NA NA
Thrombectomy 1.12 0.85–1.47 0.414 NA NA NA
Length of hospital stay 1.03 1.02–1.04 <0.001 1.04 1.01–1.06 0.005
Discharge disposition
Home without services Ref Ref Ref Ref Ref Ref
Home with services 1.60 1.22–2.11 0.001 1.35 0.58–3.16 0.489
Rehab or nursing home 2.74 2.18–3.44 <0.001 2.77 1.34–5.76 0.006
Other 1.81 1.04–3.15 0.037 1.87 0.42–8.37 0.412

AIS, acute ischemic stroke; ICH, intracerebral hemorrhage; NIHSS, National Institutes of Health Stroke Scale; IV, intravenous.

Table 3.
Association of stroke type (ICH vs. AIS) with venous thromboembolism readmission in Cox regression models
Hazard ratio 95% Confidence interval P>|t|
Unadjusted model <0.001
 AIS 1.00 Ref.
 ICH 2.56 2.28–2.87
Adjusted* model <0.001
 AIS 1.00 Ref.
 ICH 2.10 1.67–2.65
Propensity score* matching† <0.001
 AIS 1.00 Ref.
 ICH 1.89 1.34–2.66
Propensity weighted* analysis <0.001
 AIS 1.00 Ref.
 ICH 2.86 1.93–4.25

ICH, intracerebral hemorrhage; AIS, acute ischemic stroke; NIHSS, National Institutes of Health Stroke Scale.

* Adjusted, matched, and weighted for obesity, cancer, NIHSS score, atrial fibrillation or flutter, length of hospital stay, and discharge disposition;

† Without replacement.

TOOLS
Similar articles