Stroke is the fourth leading cause of death in the United States, affecting 795,000 people each year according to the Centers for Disease and Prevention and Prevention (Goldstein & Rothwell, 2012). Ischemic stroke accounts for 87% of all strokes (Go et al., 2013), and cardioembolism resulting from AF is responsible for 15%-20% of ischemic strokes (Centers for Disease Control and Prevention, 2010). Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and one in four individuals aged 40 years will develop AF during his or her lifetime (You et al., 2012). Ischemic strokes occurring in patients with AF are more severe than in patients without AF (Dulli, Stanko, & Levine, 2003).
Treatment of Acute Ischemic Stroke
Intravenous recombinant tissue plasminogen activator (rtPA) is a widely accepted treatment for stroke approved by the U.S. Food and Drug Administration since 1996 that improves functional recovery of stroke survivors with no effect on mortality (Lansberg, 2012). The major limitation of this intervention is the narrow treatment window of 0-3 hours from stroke symptom onset. Only 3%-5% of patients experiencing stroke symptoms arrive at a hospital in time to be considered for this treatment (American Stroke Association, 2012a). Delays in seeking medical treatment for stroke can severely limit the treatment options. Poor public unawareness of time-sensitive treatments or patient denial of stroke symptoms may be responsible for the small percentage of patients who arrive to the hospital in time for intravenous rtPA. The probability of a good functional outcome is directly related to shortened time to administration of intravenous rtPA.
Risk Factors and Outcome in Ischemic Stroke
Uncontrollable factors that place a person at risk for stroke include age, gender, race, family history, and prior history of stroke or transient ischemic attack (American Stroke Association, 2012b). The modifiable risk factors for stroke include hypertension, hyperlipidemia, diabetes mellitus, cigarette smoking, obesity, cardiovascular disease, physical inactivity, and AF (Goldstein et al., 2006). Stroke prevention measures and treatment options for patients with AF should be a high concern for clinicians who treat AF. Among patients with AF, the absolute risk for stroke varies 20-fold depending on patient age and other clinical features (Stroke Risk in Atrial Fibrillation Working Group, 2007).
The National Institutes of Health Stroke Scale (NIHSS) is a validated neurological scale of stroke severity that is standardized and administered by a broad range of healthcare providers (Frankel et al., 2000). Increasing stroke severity based on the admission NIHSS score has been shown to correlate with mortality. Thirty-day mortality rates based on the admission NIHSS are mild stroke (NIHSS of 0-7, 4.2%), moderate stroke (NIHSS of 8-13, 13.9%), severe stroke (NIHSS of 14-21, 31.6%), and extremely severe stroke (NIHSS of 22-42, 53.5%; Fonarow et al., 2012). Little is known about the predictors of hospital discharge outcome in patients with stroke secondary to AF when treated with intravenous rtPA.
Purposes
The purposes of this study were twofold. First, we sought to directly compare patients with ischemic stroke with and without AF who were treated with intravenous rtPA. Examining risk factors and hospital discharge outcome between the two groups may help predict patients most likely to benefit from nursing interventions during acute care hospitalization. Second, we examined independent predictors of poor hospital discharge outcome (death or discharged to a skilled nursing facility, long-term acute care facility, or hospice care) in patients with stroke secondary to AF treated with intravenous rtPA. The results of this study may identify areas for future research and direct resources for treatment that may or may not be needed and/or wanted by patients and family members.
Methods
Participants
The study was approved by the Allegheny Singer Research Institute-West Penn Allegheny Hospital Institutional Review Board. A retrospective review of patients in a single-center acute stroke registry was performed. From January 2006 to December 2011, 358 patients were treated with intravenous rtPA for stroke at Allegheny General Hospital, a Primary Stroke Center certified by the Joint Commission. Inclusion criteria were (a) age >= 18 years, (b) diagnosis of stroke presenting <=3 hours from symptom onset to the emergency department, and (c) treatment with intravenous rtPA. Exclusion criteria were (a) treatment with intra-arterial thrombolysis or mechanical clot disruption/extraction by endovascular therapy either alone or in combination with intravenous rtPA and (b) presence of cerebral infarction in bilateral cerebral hemispheres.
Clinical data were collected by chart review and included age, initial stroke severity measured by NIHSS score, length of hospital stay (LOS), gender, hypertension, hyperlipidemia, diabetes mellitus, smoking status, right versus left hemisphere infarction, intubation, AF, and hospital discharge outcome. Radiographic data included the cerebral vascular territory of infarction by magnetic resonance imaging or computerized tomography. All patients received routine standard of care for the administration of intravenous rtPA as outlined in the Guidelines for Early Management of Adults with Ischemic Stroke (Adams et al., 2007).
Procedure
A descriptive, correlational design was used with secondary analysis of data from an existing database of patients with stroke treated with intravenous rtPA. Data for the database were collected retrospectively because patients' inpatient stroke evaluation can reveal preexisting conditions not diagnosed before the stroke. A vascular neurologist (A. T.) and nurse coordinator (M. T.) were responsible for maintaining the database. A data collection form was developed and used to collect the information. The information was then transferred into the database. All data points used in this study were preexisting and were analyzed.
Instruments
Stroke severity was rated by the admission NIHSS, which is an efficient and reliable measure of a patient's neurological status because of stroke and is used to assess outcome after a stroke (Summers et al., 2009). NIHSS scores were rated by individuals who completed online training and certification through the American Stroke Association. The NIHSS is a 13-item test designed to assess a patient's neurological function and assign a score to the patient's severity of stroke. The scoring can range from 0 to 42 (0 = normal, no deficit to 42 = the greatest disability). A higher score indicates greater stroke severity and more disability.
Magnetic resonance imaging and computerized tomography brain images were reviewed by a vascular neurologist (A. T.) after treatment with intravenous rtPA to determine the radiographic extent of cerebral infarction. Large areas of cerebral infarction were defined as total anterior circulation infarction (TACI) using the Oxfordshire Community Stroke Project clinical classification of subtypes of cerebral infarction (Lindley, Wardlaw, Dennis, Slattery, & Sandercock, 1993).
Hospital discharge outcome was dichotomized as good or poor outcome in which good outcome was defined as hospital discharge to home or inpatient rehabilitation or signed oneself out against medical advice. Poor outcome was defined as in-hospital death or discharge to a skilled nursing facility, long-term acute care facility, or hospice care.
Statistical Analysis
SPSS (version 19, SPSS Inc.) was used for the analysis. Frequencies and descriptive statistics were performed to describe the patients receiving intravenous rtPA for stroke with and without AF. The t test was used to compare patients with AF versus no AF on continuous level data. A chi-square test was done to compare patients with AF versus no AF on categorical level data. A bivariate logistic regression was then conducted of the AF cohort to determine predictors of poor hospital discharge outcome. Finally, a multivariate logistic regression was performed of the AF cohort to assess independent predictors of poor hospital discharge outcome.
Results
As shown in Table 1, there were significant differences between the patients with ischemic stroke with AF (n = 144) and without AF (n = 190) who were treated with intravenous rtPA. The patients with AF compared with those without AF were older (79.4 vs. 66.5 years, p < .0001), had higher initial NIHSS scores (14.2 vs. 11.3, p < .0001), had longer LOS (8.8 vs. 6.2 days, p < .0001), were more likely women (59.7% vs. 46.8%, p = .020), had more hypertension (88.9% vs. 78.8%, p = .015), had less hyperlipidemia (63.2% vs. 78.7%, p = .002), had less cigarette smoking (19.3% vs. 41.3%, p < .0001), had higher rates of TACI (25.7% vs. 12.7%, p = .003), and had poor hospital discharge outcome (45.1% vs. 17.9%, p < .0001).
Table 2 shows the results of the bivariate logistic regression analysis to determine predictors of poor hospital discharge outcome in patients with stroke with AF treated with intravenous rtPA. Age (OR = 0.898, 95% CI [0.853, 0.945]), initial NIHSS scores (OR = 0.895, 95% CI [0.838, 0.955]), LOS (OR = 0.936, 95% CI [0.888, 0.987]), intubation (OR = 0.042, 95% CI [0.005, 0.331]), and TACI (OR = 0.053, 95% CI [0.017, 0.163]) were significant unadjusted predictors of poor hospital discharge outcome.
Employing a multivariate logistic regression analysis, age (OR = 0.879, 95% CI [0.804, 0.961]), LOS (OR = 0.925, 95% CI [0.858, 0.997]), and TACI (OR = 0.097, 95% CI [0.022, 0.432]) were significant independent predictors of poor outcome (Table 3).
Discussion
The main findings of this study are that patients with stroke with AF who are treated with intravenous rtPA are older, present with more severe strokes, and have a poorer clinical response to intravenous rtPA resulting in longer LOS, TACI (larger cerebral infarct), and poor hospital discharge outcomes in comparison with patients without AF. In addition, we found that increasing age, longer LOS, and TACI are significantly associated with poor hospital discharge outcome in patients with stroke secondary to AF.
Prior reports of patients with stroke with AF treated with intravenous rtPA have reported various outcomes measures (i.e., NIHSS, mortality, and the modified Rankin Scale score) administered at varied time points from discharge to 90 days after discharge (Banks & Marotta, 2007; Frank, Fulton, Weimar, Shuaib, & Lees, 2012; Kimura et al., 2009; Saposnik, Gladstone, Raptis, Zhou, & Hart, 2013). Similar to these reports, we found that increasing age and stroke severity based on the admission NIHSS scores are independently associated with poor outcomes (Frank et al., 2012; Kimura et al., 2009). Frank et al., however, reported that AF was not independently associated with adverse outcome after adjustment for age and stroke severity based on the day-90 modified Rankin Scale score. Saposnik et al. reported on 316 patients with stroke with AF treated with intravenous rtPA and found older age and more severe strokes compared with non-AF patients with worse outcomes (hospital-discharge modified Rankin Scale score = 3-6). We reported adverse outcomes based on the hospital discharge outcome.
Several risk factors were significantly different between patients with stroke with and without AF who were treated with intravenous rtPA and contributed to a significantly poor outcome in the patients with AF. The patients with AF tended to be older women with hypertension who had TACI (large cerebral infarct), worse initial NIHSS scores, and longer LOS. The Stroke Risk in Atrial Fibrillation Working Group (2007) found that patient age was a consistent independent risk factor for stroke in patients with AF. The AF is a prevalent chronic cardiac condition, and typically, these patients are under the medical care of specialists; therefore, their modifiable risk factors (i.e., diabetes and hypertension) may be closely monitored and treated. In contrast, we found increased rates of hyperlipidemia and smoking in the non-AF cohort compared with the AF cohort. One possible reason for the significantly higher rate of hyperlipidemia in the non-AF cohort was that these patients were younger and may be unaware of the condition. The higher rate of smoking in the non-AF cohort may be because of the higher rate of large vessel atherosclerotic disease as the cause of stroke. More community outreach and education at the primary care level can increase awareness of risk factors that people can control to prevent ischemic stroke.
Significant unadjusted characteristics that predicted poor outcome in the AF cohort were older age, more disabling strokes (TACI), and more severe strokes (higher NIHSS score). These factors contributed to the significantly greater likelihood of intubation and longer LOS in the patients with AF with poor hospital discharge outcome. In the adjusted analyses, only age, TACI, and LOS remained significant independent predictors. Patients with stroke secondary to AF with a poor hospital discharge outcome were 12% more likely to be older, 90% more likely to have TACI, and 7% more likely to have a longer LOS. As Dulli et al. (2003) reported, strokes secondary to AF are more severe than non-AF-related strokes. Prevention of stroke in the population with AF should be the primary focus of clinicians who see and treat this population. Treatment options for AF, especially in the older population, remain controversial despite advances and newer anticoagulants (Furie et al., 2012). Clinical trials support the use of warfarin and oral non-vitamin-K antagonist anticoagulants for patients with AF (Goldstein & Rothwell, 2012). The novel anticoagulants include the direct thrombin inhibitor, dabigatran, and factor Xa inhibitors rivaroxaban and apixaban, recently approved by the Food and Drug Administration for stroke prevention in AF. These new anticoagulants were tested in clinical trials against warfarin for the prevention of stroke secondary to AF. This new research helps support both novel and established therapies and improves strategies to add to the success of modern stroke prevention (Goldstein & Rothwell, 2012).
Strengths and Limitations
A strength of the study was that the NIHSS, a standardized tool, was administered by certified personnel. In addition, the patient population was recruited from a primary stroke center certified by the Joint Commission that used standardized protocols for the administration of intravenous rtPA. The sample size was moderate with fairly comparable numbers of patients in the AF and non-AF cohorts.
Limitations to this study included the secondary analysis of existing data; therefore, data were incomplete at times. Cause-and-effect relationships cannot be made because of the descriptive correlational design. Outcome was based on hospital discharge outcome, rather than a 3-month modified Rankin scoring, which is generally reported for stroke outcome but was not available. Findings can only be generalized to patients with stroke secondary to AF treated with intravenous rtPA.
Implications for Nursing
Stroke is a challenging disease that requires the efforts and skill of all members of the multidisciplinary team (Summers et al., 2009). Our results indicate two nonmodifiable variables that predict poor hospital discharge outcome in this AF stroke cohort: TACI (large cerebral infarct) and age. However, we found this group to have a longer LOS, on which nursing can have a significant impact. Neuroscience nurses often will coordinate the care of patients with stroke. Effective coordinated care of patients with stroke results in decreased LOS, improved outcomes, and decreased costs (Summers et al., 2009). Nursing can provide quality care by initiating the development of a daily multidisciplinary meeting that starts within 24 hours after hospital admission. Important members of the multidisciplinary team should include, but are not limited to, nursing; physical, occupational, and speech therapy; case management; and social work. Preexisting admission order sets can improve the process of managing the care of the patient with stroke, regardless of the etiology of the stroke or prognosis of the patient. If nurses coordinate the care across the healthcare continuum and start the stroke rehabilitation early in the inpatient setting, then the likelihood of death and disability within the first year is reduced (Miller et al., 2010). Discharge planning and anticipating the needs of this vulnerable population can help the transition at discharge for patients and their families. Outpatient care is equally important because this setting is ideal to educate patients and families about adhering to medications, controlling the modifiable risk factors that put the patients at risk for stroke or a second stroke, and activating emergency services quickly at the onset of stroke symptoms.
Conclusions
With the aging population in the United States, healthcare providers will be confronted with an increasing stroke burden. AF is a severe chronic condition that was found in this study to be associated with poor hospital discharge outcome in patients with stroke treated with intravenous rtPA. This study suggested that these patients have a high probability of being severely disabled and requiring the care and assistance of another person. The independent predictors of poor hospital discharge outcome in these patients (older age, TACI, and longer LOS) may possibly be used to help counsel patients and families and may potentially add important information to end-of-life discussions, if indicated.
Acknowledgments
The authors wish to acknowledge Denise Charron-Prochownik, PhD, RN, CPNP, FAAN, Professor of Nursing at the University of Pittsburgh, for reviewing the manuscript.
References