Organized Outpatient Care
Stroke Prevention Clinic Referrals Are Associated With Reduced Mortality After Transient Ischemic Attack and Ischemic Stroke
Background and Purpose—Organized inpatient stroke care decreases mortality and morbidity irrespective of patient age, stroke severity, or stroke subtype. Limited information is available on whether organized outpatient care models such as stroke prevention clinics (SPC) improve outcomes after a transient ischemic attack or ischemic stroke. We compared 1-year mortality and stroke readmission in patients with transient ischemic attack or ischemic stroke referred versus not referred to an SPC.
Methods—This was a retrospective cohort study including 16 468 consecutive patients with ischemic stroke or transient ischemic attack who were seen in the emergency department or admitted to a hospital between July 1, 2003 and March 31, 2008 at registry stroke centers (n=12) in the province of Ontario. Cox proportional hazards models and propensity score-matched analyses were used to evaluate 1-year mortality and readmission.
Results—One-year mortality rates were lower in those referred to SPCs compared with those not referred, even after adjustment for age, sex, ethnic origin, income, comorbid conditions, stroke symptoms and severity, receipt of thrombolysis, stroke unit care, discharge destination, and functional status at discharge (adjusted hazard ratio [HR], 0.67; 95% CI, 0.60–0.75). Survival analysis after propensity matching showed a 26% reduction in 1-year mortality (HR, 0.74; 95% CI, 0.65–0.84). There were no significant differences in 1-year readmission rates in those referred versus not referred to SPCs.
Conclusions—Referral to an SPC is associated with a one-quarter reduction in mortality after ischemic stroke or transient ischemic attack. This supports the argument that outpatient stroke units may prove as effective as their inpatient counterparts.
For patients and family members, stroke is a major life-altering event. It is a leading cause of mortality and carries one of the highest levels of disability internationally.1 Organized inpatient care has been shown to decrease morbidity and mortality.2 In addition, data from observational studies3,4 suggest that rapid outpatient stroke assessment leads to improved outcomes. However, limited evidence is available on the benefits of organized outpatient stroke care in the form of specialized stroke prevention clinics (SPC) following an initial hospital assessment. Analyses from large databases have shown that the risk of stroke after a transient ischemic attack (TIA) may be as high as 12% in the first 30 days,5 and 10% to 20% at 3 months, with 50% of strokes occurring in the first 24 to 48 hours.6,7 In addition, the risk of myocardial infarction can be as high as 30% in the 10 years following a cerebrovascular event.8,9
It has been estimated that even modest improvements in stroke prevention within Ontario could avoid >7000 deaths and save $500 million over 5 years.10 Through the Ontario Stroke System, the Ontario Ministry of Health and Long-Term Care established 24 SPCs beginning in 2001. SPCs were developed to facilitate early assessment, diagnosis, and treatment of patients with recent transient ischemic attack or nondisabling stroke.11
We undertook a study to evaluate the effect of stroke prevention clinic referral on mortality and readmissions after an initial stroke admission.
The Registry of the Canadian Stroke Network collects detailed clinical information on all consecutive patients seen in the emergency department or admitted to 12 specialized stroke centers in the province of Ontario, Canada.12 Approximately 20% of all stroke/TIA cases in the province are seen at these tertiary care centers. Patients are identified by on-site research coordinators who collect data through retrospective chart abstraction using laptop computers and custom software. The database includes detailed information on patient demographics; stroke symptoms and signs; comorbid conditions; and in-hospital treatments, complications, and outcomes. Stroke severity is measured using the Canadian Neurological Scale, which measures level of consciousness, aphasia, orientation, and motor strength and has a maximum score of 11.5; scores below 8 generally indicate a moderate-to-severe stroke.12 Functional status at discharge is measured using the modified Rankin score.13 The database also captures whether a patient is referred to an SPC at the time of discharge. Repeat chart abstraction has shown excellent agreement for key variables in the database, including age, sex, and stroke type.14 The data collection software forces chart abstraction personnel to obtain complete information on age, sex, stroke type, and other key variables before the case record can be submitted for inclusion in the database; this ensures that there are no missing data for these data elements. The Registry of the Canadian Stroke Network is prescribed under provincial privacy legislation, and patient data are collected without consent. Ethics approval for the overall project was provided by the Sunnybrook Health Sciences Research Ethics Board, and approval was also provided by the Research Ethics Board of each participating site.
The Registry of the Canadian Stroke Network data are housed at the Institute for Clinical Evaluative Sciences in Ontario, where they are linked to provincial administrative databases using unique patient identifying numbers. We used the Registered Persons Database, which provides information on all deaths regardless of patient location, to capture all-cause mortality after the index stroke event. We used the Discharge Abstract Database and the National Ambulatory Care Reporting System database, both maintained by the Canadian Institute for Health Information, to capture hospital admissions and emergency department visits for ischemic stroke or TIA, respectively, using the International Classification of Diseases-10 (ICD-10) codes I60, I61, I63, I64, and G45 (5 digits; eg, I63.x1). We used the physician claims database to capture outpatient physician visits and procedures and the Ontario Drug Benefits database to capture medication prescriptions in those age >65 years.
For the primary analysis, we included all patients with ischemic stroke or TIA seen in the emergency department or admitted to a hospital between July 1, 2003 and March 31, 2008 at 12 registry stroke centers. Patients with hemorrhagic stroke, in-hospital stroke, and invalid health card numbers were excluded, as were those who died during the index hospitalization and those missing data on stroke severity and functional status at discharge. For patients who had more than one stroke event during the study time frame, only the first stroke event was included.
Our primary outcome was all-cause mortality at 1 year after the index hospital visit for stroke or TIA. Mortality was chosen as the main outcome measure as it is clinically relevant, unbiased, and readily available in our databases. Secondary outcomes were: readmission for stroke or TIA within 1 year of the index hospital visit; the proportion of patients undergoing neuroimaging, carotid imaging, and carotid endarterectomy within 6 months of stroke presentation; the proportion of patients prescribed antihypertensive and lipid-lowering therapy within 6 months of stroke presentation; and the number of physician visits within 6 months of stroke presentation.
The study cohort was linked with the provincial administrative database to capture longitudinal data on hospital readmissions and on the use of diagnostic and treatment procedures. Database linkage was performed using unique encrypted patient identifiers (a scrambled version of the provincial health insurance card number). We documented readmissions and emergency department visits using linkages to the Discharge Abstract Database and National Ambulatory Care Reporting System, respectively, using ICD-10 diagnosis codes for stroke (I60, I61, I63, I64, H341) and TIA (G45, excluding G45.4). We captured carotid endarterectomy procedures using linkages to the Discharge Abstract Database and ICD-10 CCI procedure code 1JE57^, and captured outpatient diagnostic investigations through linkages to the Ontario Health Insurance Plan database of physician fee codes (Supplemental Appendix; http://stroke.ahajournals.org). We identified prescriptions for medications in those age >65 years using the Ontario Drug Benefit database, which contains information on drug prescriptions, including the quantity and dates of drug dispensed as well as the number of days supplied from each prescription. We used the Statistics Canada Postal Code Conversion File to link each patient to the dissemination area of his or her principal residence and imputed socioeconomic status based on the median income of neighborhood of residence.
We compared baseline characteristics between those referred and not referred to SPCs, using t-tests for continuous variables and χ2 tests for categorical variables. Cox proportional hazards models were used to compare time-to-death in those referred and not referred to SPCs, with adjustment for demographic and clinical factors (see details in following paragraph). Stratified analyses were also performed by stroke subtype (ischemic stroke versus TIA).
Because of the possibility of residual confounding even with multivariate analyses, secondary analyses were performed using a propensity-matched sample. For the propensity score analysis, a multivariate logistic regression model that predicted SPC follow-up among all ischemic stroke/TIA patients was generated. Demographic and clinical variables included in the model were age, sex, living with others or not, urban or rural residence, socioeconomic status (based on neighborhood income), stroke subtype, weakness on presentation, Oxfordshire Community Stroke Project classification, stroke severity based on Canadian Neurological Score, assessment by a stroke specialist in hospital, treatment with thrombolysis, preadmission independence, nursing home residence, comorbid conditions previous to presentation (diabetes, hypertension, congestive heart failure, myocardial infarction, atrial fibrillation, dementia, stroke, hyperlipidemia), hospital admission, stroke unit admission, residual neurological deficit at discharge, and modified Rankin score at discharge. The full Rankin score is captured in the database; we dichotomized for the purposes of the analyses. The predicted probability of SPC follow-up (ie, propensity score) was then calculated for each patient. A greedy matching algorithm was used to match SPC patients with non-SPC patients within a caliper of 0.2 SD of the logit of the propensity score, with a matching ratio of 1:1. To determine whether the propensity-score approach achieved balance in potential confounders, we compared the proportions of each covariate considered in the multivariate risk adjustment model between SPC and non-SPC patients. Evidence of imbalance in potential confounders was identified by examining the reduction in absolute standardized differences. The adequate balance was defined as absolute standardized difference less than 0.1. In the final propensity-score-matched sample, we compared secondary outcomes between those referred and not referred to secondary SPCs, using paired t-tests for continuous variables and McNemar tests for binary variables; and the primary outcomes using a Cox proportional hazards model with robust variance estimator to account for matching.15,16
All analyses were conducted using SAS software (Version 9.2, SAS Institute). We used a 2-tailed P less than 0.05 as the threshold for statistical significance.
Role of Funding Source
The study sponsors had no role in the collection, analysis, or interpretation of the data, and no role in the writing of the manuscript or the decision to submit the article for publication.
The study sample was comprised of 16468 patients with ischemic stroke or TIA, of whom 7700 patients (47%) were referred for follow up at an SPC. Compared with those who were not referred, patients referred to SPCs were more likely to be younger (mean age, 69.1 versus 72.6 years); male; to reside in higher income neighborhoods and urban areas; to have had a TIA rather than ischemic stroke; to have been independent before the index event; and less likely to have a history of stroke, diabetes, atrial fibrillation, myocardial infarction, congestive heart failure or dementia, but more likely to have a history of hyperlipidemia (Table 1). The initial propensity-score matching on the baseline variables listed in Table 1 resulted in the formation of 5531 matched pairs of SPC and non-SPC patients (Table 2). Because the absolute standardized differences were all small in the matched sample (ie, absolute standardized difference≤0.02), the initial propensity-score model was not modified.
Crude 1-year mortality rates were lower in the overall sample in those referred to SPCs compared with those who were not (5.9% versus 15.5%; P<0.001), and this was true even after adjustment (adjusted HR, 0.67; 95% CI, 0.60–0.75). Findings were similar in the propensity-matched sample, with a crude 1-year mortality rate of 7.2% for those referred compared with 9.6% for not referred (P<0.001), and an HR of 0.74 (95% CI, 0.65–0.84; Figure 1). Findings were also similar in the propensity-matched samples of ischemic strokes and TIA: for ischemic stroke, a crude 1-year mortality rate of 8.0% for those referred compared with 10.6% for not referred (P<0.001) and HR of 0.74 (95% CI, 0.64–0.86); and for TIA, a crude 1-year mortality rate of 4.8% for those referred compared with 6.7% for not referred (P=0.014) and HR of 0.71 (95% CI, 0.54–0.93). However, adjusted 1-year readmissions or emergency department visits for stroke or TIA were similar in those referred to SPCs compared with those who were not (adjusted HR, 0.98; 95% CI, 0.89–1.08), with similar results in the propensity-matched sample (HR, 0.97; 95% CI, 0.88–1.08; Figure 2). In addition, patients referred to SPCs had a shorter length of stay than did nonreferred patients (average mean length of stay in days: non-SPC, 11.6 (21.7); SPC, 5.7 (12.5); P<0.001). However, we did not use length of stay for propensity-score matching, as length of stay per se is highly associated with other baseline variables that we have used already, such as stroke severity (Spearman's rank correlation coefficient=−0.49, P<0.0001), modified Rankin score (Spearman's rank correlation coefficient=0.57, P<0.0001), and age (Spearman's rank correlation coefficient=0.1, P<0.0001).
For secondary analyses, results were similar in the overall cohort and in the propensity-matched sample, so only results for the propensity-matched sample are presented. Within 6 months after the index stroke discharge, compared with those who were not referred to SPCs in the original sample, those who were referred had more physician visits (mean, 8.4 versus 7.0; P<0.001), were more likely to undergo magnetic resonance imaging (15.2% versus 10.4%; P<0.001), carotid imaging (42.1% versus 34.5%; P<0.00001), echocardiography (34.3% versus 26.4%; P<0.001), and Holter monitoring (22.3% versus 12.3%; P<0.001), and were also more likely to be prescribed antiplatelet therapy (49.2% versus 45.2%; P<0.001) and lipid-lowering therapy (73.1% versus 67.6%; P<0.001), but less likely to have carotid revascularization (2.9% versus 3.7%; P=0.019). There were no significant differences in rates of computed tomography, antihypertensive therapy, or warfarin for atrial fibrillation between the 2 groups (Table 3).
We found that referral to an SPC after an initial hospital visit for acute ischemic stroke or TIA was associated with significantly lower mortality as well as with increased use of evidence-based therapies for secondary stroke prevention.
Our findings are consistent with observational studies showing that access to rapid outpatient stroke care result in increased rates of investigations and treatments, but also in improved outcomes after TIA and minor stroke. In the SOS-TIA study, an inpatient hospital clinic with 24-hour access was established for patients identified as having TIA.3 Patients were admitted to the clinic if they experienced sudden onset of brain or retinal dysfunction that resolved within 24 hours. The EXPRESS study was an observational study nested within a population-based study of all TIA and stroke in Oxfordshire, UK,4 which examined the effect of a reduced delay to outpatient clinic assessment; they found that urgent assessment and early treatment could reduce the risk of early recurrent stroke by approximately 80%.
The mechanisms underlying the improved outcomes seen with organized outpatient stroke care are likely multifactorial13 and include more timely investigations to determine stroke etiology; initiation of appropriate interventions for secondary stroke prevention; appropriate management of comorbid illnesses, such as diabetes and cardiac disease; and access to nursing and allied health with expertise in stroke care. In Ontario, the SPCs are heterogeneous in terms of format, funding, staff, hours, resources and other operational issues. However, all clinics have protocols and mechanisms to allow diagnostic evaluation to determine potential contributing mechanisms (cardioembolic, large-vessel disease of the extracranial and intracranial vessels, small-vessel disease, coagulation defects, and cryptogenic), identification of contributing risk factors (hypertension, hyperlipidemia, tobacco use, diabetes), and completion of the evaluation in a cost-effective and safe manner. All follow the Canadian Best Practice Recommendations for Stroke Care.17
During the past few decades, there has been growing evidence that links increased patient volumes to improved outcomes in relation to complex medical and surgical procedures, including heart transplantation,18–25 but also increasingly for subspecialty clinics like anticoagulation clinics24 and heart failure clinics.25 However, the mechanisms by which these clinics result in improved outcomes remain elusive.24,25 The improved outcomes seen with SPCs may be at least partly attributable to the expertise that comes with a specialized clinic that deals with a large volume of patients with a single condition.
Understanding how best to provide secondary prevention for stroke has implications both for stroke and for other chronic diseases. As has been noted in other studies, patients misdiagnosed with TIA are often patients who nonetheless need urgent care.3 Our results indicate that an indirect benefit of SPCs may be that patients with TIA or suspected TIA receive medical attention and care of associated medical conditions such as diabetes, hypertension, and cardiac disease. Care in an SPC may result in unintended yet important access to expert care for patients with other comorbidities.
Our study has some limitations that merit comment. First, this is an observational study, so although we adjusted for many known potentially confounding variables using a variety of rigorous statistical methods, it is possible that residual confounding accounted for some of the differences in outcomes between those referred and not referred to SPCs. However, our findings were consistent in a variety of sensitivity analyses. Second, our database did not allow us to determine whether all of the patients referred to SPCs were actually seen. However, this would be likely to bias our results toward the null. Third, as is the case with other prevention clinics, such as heart failure clinics and anticoagulation clinics, we have limited information on the care and counseling provided within the SPCs, so we do not know what components of this intervention were most effective.
Future research could include careful description and comparison of specific interventions used across different clinic settings that account for such variables as patient education and adherence; clinician adherence to best practice guidelines; logistical information such as number of hours per week and staff ratio; and other contextual details at the local level that may influence practice and outcomes. It will also be important to determine whether SPCs are cost-effective because of reducing hospital and emergency department visits. Finally, it is also important to establish nonmonetary benefits of these clinics in terms of improved patient satisfaction, adherence, and access to the right care at the right time.
Our study contributes to the growing evidence that organized outpatient SPCs result in improved patient care and outcomes, including a significant reduction in mortality. Prevention is an effective way of reducing both the human and economic costs of stroke.13 Although the individual characteristics of each SPC may differ, and the setting in which they are based may preclude standardization, our study has provided additional evidence that outpatient stroke units are an important and likely cost-effective strategy for secondary stroke prevention.
The results and conclusions are those of the authors, and should not be attributed to any of the sponsoring or funding agencies. The funding agencies had no role in the design or conduct of the study or the collection, management, analysis, or interpretation of the data. The manuscript was reviewed and approved by the publications committee of the Registry of the Canadian Stroke Network.
F.W., C.O. and G.S. had the idea for the study. F.W., C.O., G.S., V.H., M.K. contributed to the study concept and design and interpreted the data. J.F. analyzed the data and had full access to all data in the study. F.W. drafted the manuscript. All authors critically revised the manuscript and have seen and approved the final version.
Sources of Funding
This study was funded by Canadian Institutes for Health Research, the Ontario Ministry of Health and Long-Term Care, and the Canadian Stroke Network. The Institute for Clinical Evaluative Sciences is supported by an operating grant from the Ontario Ministry of Health and Long-Term Care. G.S. is supported by a Clinician Scientist Award from the Heart and Stroke Foundation of Ontario. M.K.K. is supported by a New Investigator Award from the Canadian Institutes for Health Research (CIHR).
The online-only Data Supplement is available at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.111.621524/-/DC1.
- Received March 29, 2011.
- Accepted June 7, 2011.
- © 2011 American Heart Association, Inc.
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