Comparative safety of tenecteplase vs alteplase for acute ischemic stroke.

INTRODUCTION: Tenecteplase has been compared to alteplase in acute stroke randomized trials, with similar outcomes and safety measures, but higher doses of tenecteplase have been associated with higher hemorrhage rates in some studies. Limited data are available on the safety of tenecteplase outside of clinical trials. METHODS: We examined the safety measures of intracranial hemorrhage, angioedema, and serious extracranial adverse events in a 21-hospital integrated healthcare system that switched from alteplase (0.9 mg/kg, maximum dose 90 mg) to tenecteplase (0.25 mg/kg, maximum dose 25 mg) for acute ischemic stroke. RESULTS: Among 3,689 subjects, no significant differences were seen between tenecteplase and alteplase in the rate of intracranial hemorrhage (ICH), parenchymal hemorrhage, or volume of parenchymal hemorrhage. Symptomatic hemorrhage (sICH) was not different between the two agents: sICH by NINDS criteria was 2.0 % for alteplase vs 2.3 % for tenecteplase (P = 0.57), and sICH by SITS criteria was 0.8 % vs 1.1 % (P = 0.39). Adjusted logistic regression models also showed no differences between tenecteplase and alteplase: the odds ratio for tenecteplase (vs alteplase) modeling sICH by NINDS criteria was 0.9 (95 % CI 0.33 - 2.46, P = 0.83) and the odds ratio for tenecteplase modeling sICH by SITS criteria was 1.12 (95 % CI 0.25 - 5.07, P = 0.89). Rates of angioedema and serious extracranial adverse events were low and did not differ between tenecteplase and alteplase. Elapsed door-to-needle times showed a small improvement after the switch to tenecteplase (51.8 % treated in under 30 min with tenecteplase vs 43.5 % with alteplase, P < 0.001). CONCLUSION: In use outside of clinical trials, complication rates are similar between tenecteplase and alteplase. In the context of a stroke telemedicine program, the rates of hemorrhage observed with either agent were lower than expected based on prior trials and registry data. The more easily prepared tenecteplase was associated with a lower door-to-needle time.

Outcome prediction in large vessel occlusion ischemic stroke with or without endovascular stroke treatment: THRIVE-EVT.

INTRODUCTION: The THRIVE score and the THRIVE-c calculation are validated ischemic stroke outcome prediction tools based on patient variables that are readily available at initial presentation. Randomized controlled trials (RCTs) have demonstrated the benefit of endovascular treatment (EVT) for many patients with large vessel occlusion (LVO), and pooled data from these trials allow for adaptation of the THRIVE-c calculation for use in shared clinical decision making regarding EVT. METHODS: To extend THRIVE-c for use in the context of EVT, we extracted data from the Virtual International Stroke Trials Archive (VISTA) from 7 RCTs of EVT. Models were built in a randomly selected development cohort using logistic regression that included the predictors from THRIVE-c: age, NIH Stroke Scale (NIHSS) score, presence of hypertension, diabetes mellitus, and/or atrial fibrillation, as well as randomization to EVT and, where available, the Alberta Stroke Program Early CT Score (ASPECTS). RESULTS: Good outcome was achieved in 366/787 (46.5%) of subjects randomized to EVT and in 236/795 (29.7%) of subjects randomized to control (P < 0.001), and the improvement in outcome with EVT was seen across age, NIHSS, and THRIVE-c good outcome prediction. Models to predict outcome using THRIVE elements (age, NIHSS, and comorbidities) together with EVT, with or without ASPECTS, had similar performance by ROC analysis in the development and validation cohorts (THRIVE-EVT ROC area under the curve (AUC) = 0.716 in development, 0.727 in validation, P = 0.30; THRIVE-EVT + ASPECTS ROC AUC = 0.718 in development, 0.735 in validation, P = 0.12). CONCLUSION: THRIVE-EVT may be used alongside the original THRIVE-c calculation to improve outcome probability estimation for patients with acute ischemic stroke, including patients with or without LVO, and to model the potential improvement in outcomes with EVT for an individual patient based on variables that are available at initial presentation. Online calculators for THRIVE-c estimation are available at www.thrivescore.org and www.mdcalc.com/thrive-score-for-stroke-outcome.

Underdiagnosis of Isolated Systolic and Isolated Diastolic Hypertension.

Systolic and diastolic hypertension independently predict the risk of adverse cardiovascular events. It remains unclear how systolic pressure, diastolic pressure, and other patient characteristics influence the initial diagnosis of hypertension. Here, we use a cohort of 146,816 adults in a large healthcare system to examine how elevated systolic and/or diastolic blood pressure measurements influence initial diagnosis of hypertension and how other patient characteristics influence the diagnosis. Thirty-four percent of the cohort were diagnosed with hypertension within 1 year. In multivariable logistic regression of the diagnosis of hypertension, controlling for covariates, isolated systolic hypertensive measures (odds ratio [OR] 0.42 [95% confidence interval {CI} 0.41 to 0.43]) and isolated diastolic hypertensive measures (OR 0.32 [95% CI 0.31 to 0.33]) were less likely to lead to hypertension diagnosis when compared with combined hypertensive measures. Higher levels of systolic blood pressure had a greater impact on hypertension diagnosis (OR 1.77 [95% CI 1.75 to 1.79] per Z-score) than did higher levels of diastolic blood pressure (OR 1.34 [95% CI 1.32 to 1.36] per Z-score). Older age, non-white race/ethnicity, and medical comorbidities all predicted the establishment of a diagnosis of hypertension. Isolated systolic and isolated diastolic hypertension are underdiagnosed in clinical practice, and several patient-centered factors also strongly influence whether a diagnosis is made. In conclusion, our findings uncover a care gap that can be closed with increased attention to the independent influence of systolic and diastolic hypertension and the various patient-centered factors that may impact hypertension diagnosis.

Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment.

BACKGROUND AND PURPOSE: In large artery occlusion stroke, both intravenous (IV) tPA (tissue-type plasminogen activator) and endovascular stroke treatment (EST) are standard-of-care. It is unknown how often tPA causes distal embolization, in which a procedurally accessible large artery occlusion is converted to a more distal and potentially inaccessible occlusion. METHODS: We analyzed data from a decentralized stroke telemedicine program in an integrated healthcare delivery system covering 21 hospitals, with 2 high-volume EST centers. We captured all cases sent for EST and examined the relationship between IV tPA administration and the rate of distal embolization, the rate of target recanalization (modified Treatment in Cerebral Infarction scale 2b/3), clinical improvement before EST, and short-term and long-term clinical outcomes. RESULTS: Distal embolization before EST was quite common (63/314 [20.1%]) and occurred more often after IV tPA before EST (57/229 [24.9%]) than among those not receiving IV tPA (6/85 [7.1%]; P<0.001). Distal embolization was associated with an inability to attempt EST: after distal embolization, 26/63 (41.3%) could not have attempted EST because of the new clot location, while in cases without distal embolization, only 8/249 (3.2%) were unable to have attempted EST (P<0.001). Among patients who received IV tPA, 13/242 (5.4%) had sufficient symptom improvement that a catheter angiogram was not performed; 6/342 (2.5%) had improvement to within 2 points of their baseline NIHSS. At catheter angiogram, 2/229 (0.9%) of patients who had received tPA had complete recanalization without distal embolization. Both IV tPA and EST recanalization were associated with improved long-term outcome. CONCLUSIONS: IV tPA administration before EST for large artery occlusion is associated with distal embolization, which in turn may reduce the chance that EST can be attempted and recanalization achieved. At the same time, some IV tPA-treated patients show symptomatic improvement and complete recanalization. Because IV tPA is associated with both distal embolization and improved long-term clinical outcome, there is a need for prospective clinical trials testing the net benefit or harm of IV tPA before EST.

Effect of Systolic and Diastolic Blood Pressure on Cardiovascular Outcomes.

BACKGROUND: The relationship between outpatient systolic and diastolic blood pressure and cardiovascular outcomes remains unclear and has been complicated by recently revised guidelines with two different thresholds (≥140/90 mm Hg and ≥130/80 mm Hg) for treating hypertension. METHODS: Using data from 1.3 million adults in a general outpatient population, we performed a multivariable Cox survival analysis to determine the effect of the burden of systolic and diastolic hypertension on a composite outcome of myocardial infarction, ischemic stroke, or hemorrhagic stroke over a period of 8 years. The analysis controlled for demographic characteristics and coexisting conditions. RESULTS: The burdens of systolic and diastolic hypertension each independently predicted adverse outcomes. In survival models, a continuous burden of systolic hypertension (≥140 mm Hg; hazard ratio per unit increase in z score, 1.18; 95% confidence interval [CI], 1.17 to 1.18) and diastolic hypertension (≥90 mm Hg; hazard ratio per unit increase in z score, 1.06; 95% CI, 1.06 to 1.07) independently predicted the composite outcome. Similar results were observed with the lower threshold of hypertension (≥130/80 mm Hg) and with systolic and diastolic blood pressures used as predictors without hypertension thresholds. A J-curve relation between diastolic blood pressure and outcomes was seen that was explained at least in part by age and other covariates and by a higher effect of systolic hypertension among persons in the lowest quartile of diastolic blood pressure. CONCLUSIONS: Although systolic blood-pressure elevation had a greater effect on outcomes, both systolic and diastolic hypertension independently influenced the risk of adverse cardiovascular events, regardless of the definition of hypertension (≥140/90 mm Hg or ≥130/80 mm Hg). (Funded by the Kaiser Permanente Northern California Community Benefit Program.).

Detection of Anterior Circulation Large Artery Occlusion in Ischemic Stroke Using Noninvasive Cerebral Oximetry.

BACKGROUND AND PURPOSE: Large artery occlusion (LAO) in ischemic stroke requires recognition and triage to an endovascular stroke treatment center. Noninvasive LAO detection is needed to improve triage. METHODS: Prospective study to test whether noninvasive cerebral oximetry can detect anterior circulation LAO in acute stroke. Interhemispheric ΔBrSO2 in LAO was compared with controls. RESULTS: In LAO stroke, mean interhemispheric ΔBrSO2 was -8.3±5.8% (n=19), compared with 0.4±5.8% in small artery stroke (n=17), 0.4±6.0% in hemorrhagic stroke (n=14), and 0.2±7.5% in subjects without stroke (n=19) (P<0.001). Endovascular stroke treatment reduced the ΔBrSO2 in most LAO subjects (16/19). Discrimination of LAO at a -3% ΔBrSO2 cut had 84% sensitivity and 70% specificity. Addition of the G-FAST clinical score (gaze-face-arm-speech- time) to the BrSO2 measure had 84% sensitivity and 90% specificity. CONCLUSIONS: Noninvasive cerebral oximetry may help detect LAO in ischemic stroke, particularly when combined with a simple clinical scoring system.

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.

Treatment of chronic subdural hematomas with subdural evacuating port system placement in the intensive care unit: evolution of practice and comparison with bur hole evacuation in the operating room.

OBJECTIVE The aims of this study were to evaluate a multiyear experience with subdural evacuating port system (SEPS) placement for chronic subdural hematoma (cSDH) in the intensive care unit at a tertiary neurosurgical center and to compare SEPS placement with bur hole evacuation in the operating room. METHODS All cases of cSDH evacuation were captured over a 7-year period at a tertiary neurosurgical center within an integrated health care delivery system. The authors compared the performance characteristics of SEPS and bur hole placement with respect to recurrence rates, change in recurrence rates over time, complications, length of stay, discharge disposition, and mortality rates. RESULTS A total of 371 SEPS cases and 659 bur hole cases were performed (n = 1030). The use of bedside SEPS placement for cSDH treatment increased over the 7-year period, from 14% to 80% of cases. Reoperation within 6 months was higher for the SEPS (15.6%) than for bur hole drainage (9.1%) across the full 7-year period (p = 0.002). This observed overall difference was due to a higher rate of reoperation during the same hospitalization (7.0% for SEPS vs 3.2% for bur hole; p = 0.008). Over time, as the SEPS procedure became more common and modifications of the SEPS technique were introduced, the rate of in-hospital reoperation after SEPS decreased to 3.3% (p = 0.02 for trend), and the difference between SEPS and bur hole recurrence was no longer significant (p = 0.70). Complications were uncommon and were similar between the groups. CONCLUSIONS Overall performance characteristics of bedside SEPS and bur hole drainage in the operating room were similar. Modifications to the SEPS technique over time were associated with a reduced reoperation rate.

A Simple Infection Control Protocol Durably Reduces External Ventricular Drain Infections to Near-Zero Levels.

OBJECTIVE: External ventricular drains (EVDs) historically have a high rate of infection, and EVD infections are a cause of significant morbidity and mortality. We have shown previously that a simple infection control protocol reduced the rate of EVD infections during a 3-year period, and the present study examines whether infection rates were durably reduced over an additional 4 years. METHODS: Retrospective analysis of EVDs placed in the intensive care unit of a tertiary neurosurgical center over an additional 4 year follow-up period. RESULTS: In the 4-year follow-up period, 189 EVDs were placed in 173 patients. The previously observed decrease in cerebrospinal fluid culture positivity from 9.8% in the baseline period to 0.8% in the first 3 years of the protocol period continued in the 4-year follow-up period (0%, 0 of 189 EVD placements, 0 per 1000 catheter-days; P < 0.001 compared with baseline). The previously observed decrease in the rate of ventriculitis from 6.3% to 0.8% also continued in the follow-up period (0%, 0 of 189 EVD placements, 0 per 1000 catheter-days; P < 0.001 compared with baseline). Over the total 7 years of protocol use, the rate of culture positivity was 0.3% (1 of 308 EVD placements, 0.29 per 1000 catheter-days) and the rate of ventriculitis was 0.3% (1 of 308 EVD placements, 0.29 per 1000 catheter-days). The only observed infection over 7 years occurred in a patient who removed their own EVD. CONCLUSIONS: A straightforward EVD infection control protocol substantially and durably reduces EVD infections to a near-zero rate.

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.

Improved ischemic stroke outcome prediction using model estimation of outcome probability: the THRIVE-c calculation.

BACKGROUND AND PURPOSE: The Totaled Health Risks in Vascular Events (THRIVE) score is a previously validated ischemic stroke outcome prediction tool. Although simplified scoring systems like the THRIVE score facilitate ease-of-use, when computers or devices are available at the point of care, a more accurate and patient-specific estimation of outcome probability should be possible by computing the logistic equation with patient-specific continuous variables. METHODS: We used data from 12 207 subjects from the Virtual International Stroke Trials Archive and the Safe Implementation of Thrombolysis in Stroke - Monitoring Study to develop and validate the performance of a model-derived estimation of outcome probability, the THRIVE-c calculation. Models were built with logistic regression using the underlying predictors from the THRIVE score: age, National Institutes of Health Stroke Scale score, and the Chronic Disease Scale (presence of hypertension, diabetes mellitus, or atrial fibrillation). Receiver operator characteristics analysis was used to assess model performance and compare the THRIVE-c model to the traditional THRIVE score, using a two-tailed Chi-squared test. RESULTS: The THRIVE-c model performed similarly in the randomly chosen development cohort (n = 6194, area under the curve = 0·786, 95% confidence interval 0·774-0·798) and validation cohort (n = 6013, area under the curve = 0·784, 95% confidence interval 0·772-0·796) (P = 0·79). Similar performance was also seen in two separate external validation cohorts. The THRIVE-c model (area under the curve = 0·785, 95% confidence interval 0·777-0·793) had superior performance when compared with the traditional THRIVE score (area under the curve = 0·746, 95% confidence interval 0·737-0·755) (P < 0·001). CONCLUSION: By computing the logistic equation with patient-specific continuous variables in the THRIVE-c calculation, outcomes at the individual patient level are more accurately estimated. Given the widespread availability of computers and devices at the point of care, such calculations can be easily performed with a simple user interface.