Statin Adherence Is Associated With Reduced Recurrent Stroke Risk in Patients With or Without Atrial Fibrillation.

BACKGROUND AND PURPOSE: Outpatient statin use reduces the risk of recurrent ischemic stroke among patients with stroke of atherothrombotic cause. It is not known whether statins have similar effects in ischemic stroke caused by atrial fibrillation (AFib). METHODS: We studied outpatient statin adherence, measured by percentage of days covered, and the risk of recurrent ischemic stroke in patients with or without AFib in a 21-hospital integrated healthcare delivery system. RESULTS: Among 6116 patients with ischemic stroke discharged on a statin over a 5-year period, 1446 (23.6%) had a diagnosis of AFib at discharge. The mean statin adherence rate (percentage of days covered) was 85, and higher levels of percentage of days covered correlated with greater degrees of low-density lipoprotein suppression. In multivariable survival models of recurrent ischemic stroke over 3 years, after controlling for age, sex, race/ethnicity, medical comorbidities, and hospital center, higher statin adherence predicted reduced stroke risk both in patients without AFib (hazard ratio, 0.78; 95% confidence interval, 0.63-0.97) and in patients with AFib (hazard ratio, 0.59; 95% confidence interval, 0.43-0.81). This association was robust to adjustment for the time in the therapeutic range for international normalized ratio among AFib subjects taking warfarin (hazard ratio, 0.61; 95% confidence interval, 0.41-0.89). CONCLUSIONS: The relationship between statin adherence and reduced recurrent stroke risk is as strong among patients with AFib as it is among patients without AFib, suggesting that AFib status should not be a reason to exclude patients from secondary stroke prevention with a statin.

Impact of Increased Early Statin Administration on Ischemic Stroke Outcomes: A Multicenter Electronic Medical Record Intervention.

BACKGROUND: Statin administration early in ischemic stroke may influence outcomes. Our aim was to determine the clinical impact of increasing statin administration early in ischemic stroke hospitalization. METHODS AND RESULTS: This is a retrospective analysis of a multicenter electronic medical record (EMR) intervention to increase early statin administration in ischemic stroke across all 20 hospitals of an integrated healthcare delivery system. A stroke EMR order set was modified from an "opt-in" to "opt-out" mode of statin ordering. Outcomes were mortality by 90 days, discharge disposition, and increase in stroke severity. We examined the relationship between intervention and outcome using autoregressive integrated moving average (ARIMA) time-series modeling. The EMR intervention increased both overall in-hospital statin administration (from 87.2% to 90.7%, P<0.001) and early statin administration (from 16.9% to 26.3%, P<0.001). ARIMA models showed a small increase in the rate of survival (difference in probability [Pdiff]=0.02, P=0.016) and discharge to home or rehabilitation facility (Pdiff=0.04, P=0.034) associated with the intervention. The increase in statin administration <8 hours was associated with much larger increases in survival (Pdiff=0.17, P=0.033) and rate of discharge to home or rehabilitation (Pdiff=0.29, P=0.011), as well as a decreased rate of neurological deterioration in-hospital (Pdiff=-0.14, P=0.026). CONCLUSIONS: A simple EMR change increased early statin administration in ischemic stroke and was associated with improved clinical outcomes. This is, to our knowledge, the first EMR intervention study to show that a modification of an electronic order set resulted in improved clinical outcomes.

Effect of statin use during hospitalization for intracerebral hemorrhage on mortality and discharge disposition.

IMPORTANCE: Statin use during hospitalization is associated with improved survival and a better discharge disposition among patients with ischemic stroke. It is unclear whether inpatient statin use has a similar effect among patients with intracerebral hemorrhage (ICH). OBJECTIVE: To determine whether inpatient statin use in ICH is associated with improved outcomes and whether the cessation of statin use is associated with worsened outcomes. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 3481 patients with ICH admitted to any of 20 hospitals in a large integrated health care delivery system over a 10-year period. Detailed electronic medical and pharmacy records were analyzed to explore the association between inpatient statin use and outcomes. MAIN OUTCOMES AND MEASURES: The primary outcome measures were survival to 30 days after ICH and discharge to home or inpatient rehabilitation facility. We used multivariable logistic regression, controlling for demographics, comorbidities, initial severity, and code status. In addition, we used instrumental variable modeling to control for confounding by unmeasured covariates at the individual patient level. RESULTS: Among patients hospitalized for ICH, inpatient statin users were more likely than nonusers to be alive 30 days after ICH (odds ratio [OR], 4.25 [95% CI, 3.46-5.23]; P < .001) and were more likely than nonusers to be discharged to their home or an acute rehabilitation facility (OR, 2.57 [95% CI, 2.16-3.06]; P < .001). Patients whose statin therapy was discontinued were less likely than statin users to survive to 30 days (OR, 0.16 [95% CI, 0.12-0.21]; P < .001) and were less likely than statin users to be discharged to their home or an acute rehabilitation facility (OR, 0.26 [95% CI, 0.20-0.35]; P < .001). Instrumental variable models of local treatment environment (to control for confounding by unmeasured covariates) confirmed that a higher probability of statin therapy was associated with a higher probability of 30-day survival (with an increase in probability of 0.15 [95% CI, 0.04-0.25]; P = .01) and a better chance of being discharged to home or an acute rehabilitation facility (with an increase in probability of 0.13 [95% CI, 0.02-0.24]; P = .02). CONCLUSIONS AND RELEVANCE: Inpatient statin use is associated with improved outcomes after ICH, and the cessation of statin use is associated with worsened outcomes after ICH. Given the association between statin cessation and substantially worsened outcomes, the risk-benefit balance of discontinuing statin therapy in the acute setting of ICH should be carefully considered.

High critical care usage due to pediatric stroke: results of a population-based study.

OBJECTIVES: To measure intensive care unit (ICU) admission, intubation, decompressive craniotomy, and outcomes at discharge in a large population-based study of children with ischemic and hemorrhagic stroke. METHODS: In a retrospective study of all children enrolled in a Northern Californian integrated health care plan (1993-2003), we identified cases of symptomatic childhood stroke (age >28 days through 19 years) from inpatient and outpatient electronic diagnoses and radiology reports, and confirmed them through chart review. Data regarding stroke evaluation, management, and outcomes at discharge were abstracted. Intensive care unit (ICU) admission, intubation, and decompressive neurosurgery rates were measured, and multivariate logistic regression was used to identify predictors of critical care usage and outcomes at discharge. RESULTS: Of 256 cases (132 hemorrhagic and 124 ischemic), 61% were admitted to the ICU, 32% were intubated, and 11% were treated with a decompressive neurosurgery. Rates were particularly high among children with hemorrhagic stroke (73% admitted to the ICU, 42% intubated, and 19% received a decompressive neurosurgery). Altered mental status at presentation was the most robust predictor for all 3 measures of critical care utilization. Neurologic deficits at discharge were documented in 57%, and were less common after hemorrhagic than ischemic stroke: 48% vs 66% (odds ratio 0.5, 95% confidence interval 0.3-0.8). Case fatality was 4% overall, 7% among children admitted to the ICU, and was similar between ischemic and hemorrhagic stroke. CONCLUSIONS: ICU admission is frequent after childhood stroke and appears to be justified by high rates of intubation and surgical decompression.

Practice variation in neuroimaging to evaluate dizziness in the ED.

BACKGROUND: The appropriate role of neuroimaging to evaluate emergency department (ED) patients with dizziness is not established by guidelines or evidence. METHODS: We identified all adults with a triage complaint of dizziness who were evaluated at 20 EDs of a large Northern California integrated health care program in 2008. Using comprehensive medical records, we captured all head computed tomographies (CTs) or brain magnetic resonance images (MRIs) completed at presentation or within 2 days and all stroke diagnoses within 1 week. We assessed variation in neuroimaging use by site using a random-effects logistic model to account for differences in patient- (demographic and vascular risk factors) and site-level factors (volume, % patients with dizziness, and % patients with dizziness admitted) and linear regression to assess the relationship between neuroimaging rates and stroke diagnosis rates by site. RESULTS: Of 378 992 patients seen in 2008, 20 795 (5.5%) had at least one ED visit for dizziness. Overall, 5585 patients (26.9%) had a head CT and 652 (3.1%) had a brain MRI. Between 21.8% and 32.8% of ED patients with dizziness at each site had a head CT (P<.001). For brain MRI, the range was 0.8% to 6.2%-a nearly 8-fold variation (P<.001) that persisted after adjustment for patient- and site-level factors. Higher neuroimaging rates did not translate into higher stroke diagnoses rates, with 0.7% to 2.5% of patients with dizziness diagnosed with stroke by site. CONCLUSION: The use of neuroimaging for ED patients with dizziness varies substantially without an associated improvement in stroke diagnosis, which is identified only rarely.

Statin use during ischemic stroke hospitalization is strongly associated with improved poststroke survival.

BACKGROUND AND PURPOSE: Statins reduce infarct size in animal models of stroke and have been hypothesized to improve clinical outcomes after ischemic stroke. We examined the relationship between statin use before and during stroke hospitalization and poststroke survival. METHODS: We analyzed records from 12 689 patients admitted with ischemic stroke to any of 17 hospitals in a large integrated healthcare delivery system between January 2000 and December 2007. We used multivariable survival analysis and grouped-treatment analysis, an instrumental variable method that uses treatment differences between facilities to avoid individual patient-level confounding. RESULTS: Statin use before ischemic stroke hospitalization was associated with improved survival (hazard ratio, 0.85; 95% CI, 0.79-0.93; P<0.001), and use before and during hospitalization was associated with better rates of survival (hazard ratio, 0.59; 95% CI, 0.53-0.65; P<0.001). Patients taking a statin before their stroke who underwent statin withdrawal in the hospital had a substantially greater risk of death (hazard ratio, 2.5; 95% CI, 2.1-2.9; P<0.001). The benefit was greater for high-dose (>60 mg/day) statin use (hazard ratio, 0.43; 95% CI, 0.34-0.53; P<0.001) than for lower dose (<60 mg/day) statin use (hazard ratio, 0.60; 95% CI, 0.54-0.67; P<0.001; test for trend P<0.001), and earlier treatment in-hospital further improved survival. Grouped-treatment analysis showed that the association between statin use and survival cannot be explained by patient-level confounding. CONCLUSIONS: Statin use early in stroke hospitalization is strongly associated with improved poststroke survival, and statin withdrawal in the hospital, even for a brief period, is associated with worsened survival.

Recent trauma and acute infection as risk factors for childhood arterial ischemic stroke.

OBJECTIVE: Trauma and acute infection have been associated with stroke in adults, and are prevalent exposures in children. We hypothesized that these environmental factors are independently associated with childhood arterial ischemic stroke (AIS). METHODS: In a case-control study nested within a cohort of 2.5 million children (≤19 years old) enrolled in an integrated health care plan (1993-2007), childhood AIS cases (n = 126) were identified from electronic records and confirmed through chart review. Age- and facility-matched controls (n = 378) were randomly selected from the cohort. Exposures were determined from review of medical records prior to the stroke diagnosis, or the same date for the paired controls; time windows were defined a priori. RESULTS: A medical encounter for head or neck trauma within the prior 12 weeks was an independent risk factor for childhood AIS (odds ratio [OR], 7.5; 95% confidence interval [CI], 2.9-19.3), present in 12% of cases (1.6% of controls). Median time from trauma to stroke was 0.5 days (interquartile range, 0-2 days); post hoc redefinition of trauma exposure (prior 1 week) was more strongly associated with AIS: OR, 39; 95% CI, 5.1-298. A medical encounter for a minor acute infection (prior 4 weeks) was also an independent risk factor (OR, 4.6; 95% CI, 2.6-8.2), present in 33% of cases (13% of controls). No single infection type predominated. Only 2 cases had exposure to trauma and infection. INTERPRETATION: Trauma and acute infection are common independent risk factors for childhood AIS, and may be targets for stroke prevention strategies.

Trends in usage of alternative antiplatelet therapy after stroke and transient ischemic attack.

BACKGROUND AND PURPOSE: The effects of alternative antiplatelet agents such as clopidogrel and dipyridamole have been studied in clinical trials and heavily marketed. Because public data on their usage are limited, we examined trends in their prescription after stroke and transient ischemic attack to assess the impact of marketing and trial results. METHODS: Between 2001 and 2005, 85 US hospitals prospectively enrolled all patients admitted with ischemic stroke or transient ischemic attack into a registry designed for quality improvement (Ethos). Data on rates of antiplatelet medication usage at discharge were examined over time, and trends were evaluated by the Mantel-Haenszel test. RESULTS: Among 18 020 patients included during the 4-year period, 89% were discharged on antithrombotic medication. Between the first quarter of 2001 and the first quarter of 2004, prescription of clopidogrel-aspirin doubled (P<0.0001 for trend), coincident with publication of results from CURE and CREDO showing efficacy in patients with acute coronary syndromes. Monotherapy with aspirin or clopidogrel decreased concomitantly, and use of dipyridamole-aspirin remained constant. After an increased bleeding risk was reported in the clopidogrel-aspirin arm of the MATCH trial, use of the combination decreased sharply from 31.5% in the first quarter of 2004 to 12.8% in the first quarter of 2005 (P<0.0001), while an increase was seen in the use of clopidogrel alone (7.6% to 12.8%, P=0.03) and dipyridamole-aspirin (7.4% to 20.2%, P<0.0001). CONCLUSIONS: Clopidogrel and dipyridamole-aspirin are used frequently after stroke or transient ischemic attack. Use of clopidogrel-aspirin was common in patients with recent ischemic stroke before the publication of MATCH, after which rates dramatically declined and use of dipyridamole-aspirin and clopidogrel alone increased.