RACIAL DISPARITIES IN TPA TREATMENT RATE FOR STROKE: A POPULATION-BASED STUDY

Abstract

Background

Some prior studies have shown that racial disparities exist in intravenous tissue plasminogen activator (IV tPA) utilization for acute ischemic stroke. We sought to determine whether race was associated with tPA treatment for stroke in a predominantly black urban population.

Methods

Systematic chart abstraction was performed on consecutive hospitalized ischemic stroke patients from all seven acute care hospitals in the District of Columbia from Feb 1, 2008 to Jan 31, 2009.

Results

Of 1044 ischemic stroke patients, 74%% were black, 19% non-Hispanic white, 5% received IV tPA. Blacks were one third less likely than whites to receive IV tPA (3% vs. 10%, p<0.001). However, blacks were also less likely than whites to present within 3 hours of symptom onset (13% vs. 21%, p=0.004) and also less likely to be tPA-eligible (5% vs. 13%, p<0.001). Of those who presented within 3 hours, blacks were almost half as likely to be treated with IV tPA than whites (27% vs. 46%, p=0.023). The treatment rate for tPA-eligible patients was similar for blacks and whites (70% vs. 76%, p=0.62).

Conclusions

In this predominantly black urban population hospitalized for acute ischemic stroke, blacks were significantly less likely to be treated with IV tPA due to contraindications to treatment, delayed presentation, and stroke severity. Effective interventions designed to increase treatment in this population need to focus on culturally relevant education programs designed to address barriers specific to this population.

Background

Despite significant advances in the prevention and acute treatment of cerebrovascular disease in the last few decades, stroke remains the fourth leading cause of death and the leading cause of adult disability in the United States. Intravenous tissue plasminogen activator (IV tPA) has been demonstrated to improve clinical outcome in acute ischemic stroke¹, yet only 2–5% of acute stroke patients in most communities in the United States receive this therapy^{2, 3}. In the United States there is a growing awareness, particularly among governmental institutions, of the need to address disparities in stroke care.

Mortality from stroke disproportionately affects blacks, and this disparity is found across all stroke types.⁴ Black stroke survivors also report greater stroke-related long-term disability compared to whites.⁵ A potential contributing factor leading to the racial disparities in stroke outcome is disparity in the delivery of acute stroke treatment. It remains controversial as to whether there are racial disparities in the administration of IV tPA for those patients who arrive within the 3 hour window, and there are few studies evaluating this possible race effect on acute stroke care. The purpose of this study was to determine whether there were differences in tPA treatment rate by race (black vs. non-Hispanic white) in the District of Columbia, a predominantly black urban population.

Methods

Clinical and demographic data were prospectively collected by chart abstraction on consecutive hospitalized ischemic stroke patients from all seven acute care hospitals in the District of Columbia from Feb 1, 2008 to Jan 31, 2009. At that time, 3 of the 7 hospitals were certified by the Joint Commission as Primary Stroke Centers. However, a protocol for Emergency Medical Services (EMS) transport of stroke patients to stroke centers was not in place at that time. Patients were identified by active surveillance of emergency department admissions using pre-specified stroke screening terms,⁶ and by passive surveillance of primary discharge diagnosis of acute ischemic stroke (identified by discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434.01, 434.11, 434.91, 436 and validated by chart review). Detailed data were collected on patients who arrived within three hours of symptom onset and/or were treated with IV tPA for acute stroke, including age, gender, insurance status, risk factors, National Institutes of Health Stroke Scale (NIHSS) score, tPA treatment status and tPA eligibility. If exact time of onset was not documented in the chart, then the time was estimated as follows: if onset was recorded as “AM” or “morning,” then time of onset was considered to be 8 AM; if onset was recorded as “PM” or “evening,” then onset was considered to be 8 PM; if only the day was specified, then noon of that day was used as the time of onset.⁷ A board-certified vascular neurologist (A.W.H.) reviewed charts for all <3 hour patients not treated with tPA to determine reasons for tPA exclusion.

Rates of tPA use were examined within black and non-Hispanic white ischemic stroke patients. We examined rates of tPA use among the following groups: 1) those who were eligible to receive tPA, 2) those who arrived at the hospital within three hours, and 3) patients who were not transferred from other hospitals. Within each of these groups, we examined unadjusted differences in tPA use by key factors by calculating odds ratios (ORs) and associated p-values. Age was categorized as 65 years or younger, 66 to 75, and older than 75. NIHSS score greater than 8 was considered severe. The race-tPA use rate was computed using adjusted ORs controlling for age, stroke severity and insurance. We restricted the number of adjusting factors to variables that were statistical covariates (significantly associated with tPA use, alpha < 0.1 in unadjusted analyses, and associated with race). All analyses were conducted using SAS version 9.2 (Cary, NC).

Results

All ischemic stroke patients

Of 1044 cases of confirmed ischemic stroke, 973 were included in the analysis and are heretofore referred to as “all ischemic strokes”: 80% black, 20% non-Hispanic white, 55% women, mean age 66 years. (Hispanics comprised 2.5% of confirmed ischemic strokes and races other than black or white made up <5% of patients; these patients were excluded from the analysis.) Overall, 45 patients (5%) were treated with IV tPA. Rates of tPA use were similar for men and women and across different insurance levels (Table 1). However, of all ischemic strokes, blacks were one third less likely than whites to be treated with IV tPA (3% vs. 10%, p<0.001).

Table 1.

tPA Use in Patients with Ischemic Stroke Treated at an Acute Care Hospital in the District of Columbia

Characteristics (n=973)	tPA Treated, n (%)	Univariate OR, (95% CI)
Gender
Male, n = 435	25 (6)	Ref
Female, n = 538	20 (4)	0.63 (0.35 – 1.16)
Ethnicity
White, n = 198	19 (10)	Ref
Black, n = 775	26 (3)	0.33 (0.18 – 0.60)*
Age
Age <= 65, n = 468	21 (5)	Ref
65 < Age <= 75, n = 229	14 (6)	1.39 (0.69, 2.78)
Age > 75, n = 276	10 (4)	0.80 (0.37, 1.73)
Insurance Type
Private, n = 266	16 (6)	Ref
Medicare, n = 193	6 (3)	0.50 (0.19 – 1.31)
Multiple Insurances, n = 295	14 (5)	0.78 (0.37 – 1.63)
Other, n = 219	9 (4)	0.67 (0.29 – 1.55)

Ref indicates reference category.

^*p<0.001

<3 hour patients

Fourteen percent of ischemic stroke patients arrived within 3 hours of symptom onset. There was no association between gender or insurance type and early arrival. Of those who arrived early, rates of tPA use were similar between genders and across age groups and insurance levels. However, patients with more severe strokes (NIHSS>8) were significantly more likely to be treated with tPA (adjusted OR=4.56, 95% CI: 2.00–10.35) (Table 2). Blacks were less likely than whites to present within 3 hours of symptom onset (13% vs. 21%, p=0.004). Of those who presented within 3 hours, blacks were almost 50% less likely to be treated with IV tPA than whites (27% vs. 46%, p=0.023). Adjusting for stroke severity, though there was still a trend for blacks to be less likely to receive tPA than whites, this was no longer significant (OR=0.44, 95% CI: 0.19, 1.05) (Table 2).

Table 2.

tPA Use in Patients Arriving <3 Hours from Symptom Onset

Characteristics (n=139)	tPA Treated, n (%)	Adjusted OR, (95% CI)
Gender
Male, n = 69	25 (36)
Female, n = 70	20 (29)
Ethnicity
White, n = 41	19 (46)	Ref
Black, n = 98	26 (27)	0.44 (0.19 – 1.05)
Age
Age <= 65, n = 64	21 (33)
65 < Age <= 75, n = 35	14 (40)
Age > 75, n = 40	10 (25)
Insurance Type
Private, n = 41	16 (39)
Medicare, n = 32	6 (19)
Multiple Insurances, n = 41	14 (34)
Other, n = 25	9 (36)
Stroke Severity
Mild/Moderate, n = 79	17 (22)	Ref
Severe, n = 45	24 (53)	4.56 (2.00 – 10.35)*

Ref indicates reference category.

^*p<0.001

tPA-eligible patients

Based on NINDS tPA eligibility criteria¹, 6.4% of all ischemic strokes and 45% of those arriving <3 hours were tPA eligible. Of tPA eligible patients, rates of tPA use were similar for men and women. Patients with Medicare or multiple insurances were less likely to be treated with tPA than those with private insurance (adjusted OR=0.04, 95% CI: 0.01–0.52 and adjusted OR=0.09, 95% CI: 0.01–0.96, respectively) (Table 3). Age was not associated with rate of tPA treatment. Again, patients with more severe strokes were significantly more likely to be treated with tPA (adjusted OR=7.94, 95% CI: 1.68–37.46) (Table 3).

Table 3.

tPA Use in tPA-eligible Patients

Characteristics (n=62)	tPA Treated, n (%)	Adjusted OR, (95% CI)
Gender
Male, n = 33	25 (76)
Female, n = 29	20 (69)
Ethnicity
White, n = 25	19 (76)	Ref
Black, n = 37	26 (70)	0.85 (0.21 – 3.40)
Age
Age <= 65, n = 27	21 (78)
65 < Age <= 75, n = 18	14 (78)
Age > 75, n = 17	10 (59)
Insurance Type
Private, n = 17	16 (94)	Ref
Medicare, n = 12	6 (50)	0.04 (0.01 – 0.52)*
Multiple Insurances, n = 21	14 (67)	0.09 (0.01 – 0.96)†
Other, n = 12	9 (75)	0.28 (0.02 – 3.45)
Stroke Severity
Mild/Moderate, n = 30	17 (57)	Ref
Severe, n = 28	24 (86)	7.94 (1.68 – 37.46)§

Ref indicates reference category.

^*p=0.014

^†p=0.046

^§p=0.009

Blacks were less likely to be tPA-eligible than whites (5% vs. 13%, p<0.001). Most common contraindications included being unable to establish symptom onset time or begin treatment <3h (n=27) (this includes patients who were categorized as <3 hours based on an estimated symptom onset time as well as patients who arrived 2–3 hours from symptom onset), having a nondisabling or no measurable deficit (n=27), and uncontrolled hypertension (n=8) (Table 4). An additional 10 patients had recent stroke or evidence of prior intracranial hemorrhage that excluded them from treatment. Of those who were eligible based on standard criteria, tPA was not administered to an additional 17 patients for non-standard reasons based on chart documentation including: elderly patients with mild deficits (n=4), brain imaging findings suggest stroke is >3h (n=2), and elderly patients for whom family refused treatment (n=2) (Table 4). Blacks had significantly more standard exclusions (p=0.012) and total (standard plus non-standard) exclusions (p=0.023) than whites (Table 4).

Table 4.

Reason for tPA Exclusion by Race (of patients who arrived <3 hours)

Reason For Exclusion	Race		p
	Black, n (%)	White, n (%)
Symptom onset time not well established or tPA could not be administered <3h	23 (24)	4 (10)
Nondisabling or no measurable deficit	19 (19)	8 (20)
Uncontrolled hypertension	7 (7)	1 (2)
Within 3 months of intracranial or intraspinal surgery, serious head trauma, or previous stroke	4 (4)	1 (2)
Evidence of intracranial hemorrhage on pretreatment noncontrast head CT/MRI	4 (4)	0 (0)
Acute bleeding diathesis	3 (3)	2 (5)
Recent gastrointestinal or urinary tract hemorrhage	3 (3)	1 (2)
Witnessed seizure at stroke onset	3 (3)	0 (0)
Clinical presentation suggestive of subarachnoid hemorrhage even with normal CT/MRI	2 (2)	0 (0)
Known arteriovenous malformation, neoplasm, or aneurysm	1 (1)	1 (2)
CT/MRI shows multilobar infarction (hypodensity greater than one third cerebral hemisphere)	1 (1)	0 (0)
Active internal bleeding or acute trauma (fracture)	0 (0)	1 (2)
Within 14 days of major surgery or serious trauma	0 (0)	1 (2)
Total standard exclusions	61 (62)	16 (39)	0.012
Other non-standard reasons tPA not administered
Elderly patient with mild deficit NIHSS<4 (80 yo, 80 yo, 89 yo, 100 yo)	2 (2)	2 (5)
Brain imaging findings suggest stroke is >3h	2 (2)	0 (0)
Elderly patient and family refused (93 yo, 96 yo)	1 (1)	1 (2)
Improvement in symptoms and brain imaging findings suggest reperfusion	1 (1)	0 (0)
Delay in stroke evaluation	1 (1)	0 (0)
Initial diagnosis was not stroke	1 (1)	0 (0)
Patient or family refused	0 (0)	1 (2)
Unable to determine eligibility of patient at outside hospital	0 (0)	1 (2)
Patient refused because some improvement in symptoms	0 (0)	1 (2)
No reason stated with mild deficit NIHSS<4	1 (1)	0 (0)
No reason stated	2 (2)	0 (0)
Total non-standard exclusions	11 (11)	6 (15)	0.576
Total exclusions*	72(74)	22 (54)	0.023

^*Ten patients (7 black, 3 white) had more than one exclusion

The treatment rate for tPA-eligible patients was similar for blacks and whites (70% vs. 76%, p=0.62), and adjustment for other factors did not change this result (OR= 0.85, 95% CI: 0.21, 3.40) (Table 3).

Transfer patients

Thirteen percent of the ischemic stroke patients overall were transferred from another hospital, 9% from outside of D.C. These patients were more likely to be white than black (27% vs. 9%, p<0.001). Fourteen of the 45 patients (31%) that were treated with IV tPA were transferred from another hospital (“drip and ship”); all of these patients were white from outside D.C. Excluding the transferred patients from the analysis, blacks remained significantly less likely than whites to arrive <3h (12% vs 19%, p=0.021), be tPA eligible (4% vs. 10%, p=0.01), or be treated with IV tPA (3% vs. 7%, p=0.021). The treatment rate for tPA-eligible patients remained similar for blacks and whites (68% vs. 71%, p=0.999).

Discussion

We found that in the District of Columbia, blacks hospitalized with ischemic stroke were 1/3 as likely to be treated with tPA than whites. While blacks were more likely to have delayed presentation, even for those who arrived within 3 hours of symptom onset, blacks were still half as likely to be treated with tPA than whites. Adjusting for stroke severity attenuated some but not all of this difference. Importantly, blacks were more likely to have contraindications to treatment. Of the tPA-eligible patients, the treatment rate for blacks and whites was similar (Figure 1).

Figure 1.

tPA Treatment Rate by Race, Time to Presentation, and Eligibility

A racial difference in overall tPA treatment rate has previously been shown in a study from a database of patients admitted to 137 community hospitals throughout the U.S., in which black patients were 1/2 as likely to receive IV tPA for ischemic stroke, controlling for factors including severity, physician specialty, and location (95% CI 0.31–0.95, p=0.031).³ It has also been demonstrated by Johnston et al. in a medical record review of 42 U.S. academic medical centers where blacks were one-fifth as likely to receive tPA than whites, (p=0.001), a difference that persisted after adjustment for age, gender, insurance type, and stroke severity (OR 0.21, 95% CI 0.06 to 0.68).⁸

Contrary to our results, Kleindorfer et al. found no difference in tPA utilization by race out of their overall ischemic stroke population (79% white, 21% black).⁹ However, though their study also involved multiple hospitals in one region as part of the Greater Cincinnati/Northern Kentucky Stroke Study, a single team of academic stroke physicians was responsible for making decisions regarding stroke thrombolytic treatment. Our study may be more representative of the acute stroke treatment activity of an urban environment with a mix of academic and community hospitals with a wide spectrum of acute stroke response systems.

Explanations for treatment disparities are difficult to elucidate though factors including disease awareness, access to care, socioeconomic status, patient mistrust, and clinician bias have been implicated.^{3, 8, 10–12} In our community, much of the racial differences in treatment rates for overall ischemic strokes can be explained by contraindications to treatment. Delay to hospital arrival was the most common reason patients were excluded from thrombolytic therapy, and blacks were more likely to have delayed presentation. Our finding that only 14% of all ischemic stroke patients arrived within 3 hours is similar to the findings of Katzan et al. in a retrospective cohort study of 9 hospitals within the Cleveland Clinic Health System, though they do not report whether there was a racial disparity in the proportions of patients who arrived early.² Educational campaigns to date have not been universally successful in increasing tPA treatment rates for stroke, particularly in black underserved cities such as D.C. Potential explanations may include the lack of culturally relevant educational materials and the need to address preparedness and community-specific barriers leading to delayed hospital arrival.¹³ Our findings suggest that improving the public’s stroke knowledge and recognition as well as their ability to translate this to the action of presenting emergently to the hospital could have a significant impact on tPA utilization.

Even for those in our community who arrived within 3 hours of symptom onset, blacks were still half as likely to be treated with tPA than whites (p=0.023). Adjusting for stroke severity attenuated some but not all of this difference (p=0.064). Importantly, blacks were more likely to have contraindications to treatment. Addressing basic management of stroke risk factors may increase tPA eligibility. Uncontrolled hypertension accounted for 9% of patients with absolute contraindications to treatment. An additional 10% had recent stroke or evidence of prior intracranial hemorrhage that excluded them from treatment. Improving control of traditional stroke risk factors in addition to preventing strokes could also serve to decrease the prevalence of certain common contraindications to tPA when strokes occur.

Of the tPA-eligible patients in our community, the treatment rate was similar for blacks and whites. However, tPA treatment for eligible patients was independently associated with stroke severity. While Johnston et al. did find a racial difference in treatment rate of tPA-eligible patients when looking at the country as a whole, interestingly, they found that for hospitals where a larger percentage of blacks are treated for ischemic strokes, including the Southeast region, tPA treatment rates were similar between races. This is consistent with our findings. Reasons for similar rates of treatment utilization by race where there are more blacks are not well delineated, though one could speculate that if most of the patients are black, race may not influence the practitioner’s treatment decision, i.e. reducing/eliminating physician bias, and instead other treatment-relevant factors such as stroke severity are used as the basis for making a treatment decision.

Prior studies have suggested that institutional factors may play an important role in some communities, particularly if blacks and whites receive care at different hospitals.^14–16 One study has suggested that black patients spend more time in the emergency department waiting for care than other races.¹⁷ In our study of the D.C. community as a whole, our findings do not suggest an overall bias or disparity in treatment at the institutional level. However, further studies are needed to explore these factors.

Our study has several limitations. First, data collection was not blinded to race. However it is unlikely that bias is introduced into objective variables such as time data. Second, of patients that were identified, our ability to determine circumstances surrounding tPA treatment including benchmark times and reasons for exclusion was limited to medical record documentation of variable quality. However, the need to improve documentation is an important finding that should be incorporated into future interventions at the hospital level addressing tPA administration. Third, the number of tPA-eligible patients was relatively small, so one must be cautious in drawing conclusions on this subgroup of patients. However, we have identified important factors involved in disparities with tPA treatment. Further studies with larger sample sizes are needed to better explore these findings. Finally, while the findings in our community may not reflect acute stroke care across the country, it is likely relevant to other urban centers with similar demographics.

Despite these limitations, this study adds to the existing literature by examining in detail the tPA treatment rates and specific eligibility of stroke patients by race across an entire city with a predominantly black population. Our findings highlight the complexity underlying racial treatment disparities and emphasize the importance of systemic changes when designing interventions that will affect public awareness and stroke knowledge as well as hospitals in which underserved patients are more likely to receive their care. Public interventions include the need for culturally relevant educational campaigns specifically designed to increase stroke recognition and preparedness for early arrival within this urban black population¹⁸ and improved risk factor control to maximize eligibility. These measures have the potential to increase the number of eligible patients and reduce disparities in both treatment rates and overall stroke outcomes.