Alteplase In Ischemic Stroke Patients Research Articles

Abstract P27: Safety and Efficacy of Alteplase in Ischemic Stroke Patients > 80 Years of Age in the Extended Time Window

Background: While patients > 80 years of age were originally excluded from the ECASS 3 trial showing benefit in the 3 – 4.5-hour window, recent studies have shown that intravenous alteplase is safe and benefits this population. We aimed to assess safety and efficacy of intravenous thrombolysis in stroke patients above 80 presenting both in the 3 and 3 – 4.5-hour windows. Methods: We analyzed data from 3 comprehensive stroke centers in the US of consecutive patients > 80 years of age presenting with acute ischemic stroke who received intravenous alteplase in both the 3 and 4.5-hour time windows over a 3-year period. We collected baseline demographic data, stroke severity as assessed by NIHSS scores, and use of mechanical thrombectomy (MT). Primary outcome was symptomatic intracerebral hemorrhage, as defined by ECASS 2 criteria (hemorrhagic transformation post thrombolysis with worsening of NIHSS score by ≥ 4 points). Secondary outcomes included assessment of efficacy, evaluated by good functional outcome (mRS 0 – 2) at time of discharge. Results: We identified 418 patients with ischemic stroke above 80 years (64.8% women) who received alteplase: 344 (82.3%) within 3 hour and 74 (17.7%) in the 3 to 4.5-hour window, with similar stroke severity by NIHSS scores (median [IQR] 13 [12-32] vs. 12 [6-20], p = 0.87). In addition, 147 patients received MT, 128 (37.2%) versus 19 (25.7%), (p= 0.059) in the 3 and 3-4.5-hour groups. The overall rate of sICH was 6.1% and 4.0% (p = 0.49), in the 3 and 3-4.5-hour groups, respectively. Good functional outcome was achieved in 16.7% at time of discharge, for 17.7% in the 3-hour group and for 12.2% in the 3 – 4.5-hour group (p= 0.24). Conclusions: In our multi-center cohort, the use of alteplase in patients above 80 was safe, with low sICH rates similar to the literature, irrespective of age. Given the rare occurrence of our primary outcome in a selected cohort of acute stroke patients, our study was not powered to detect a possible significant difference in sICH.

Abstract WP192: Last Known Well to Arrival Times in Midwest Hospitals Indicate Need for Further Community Education

Background & Objectives: Timely administration of IV Alteplase in ischemic stroke patients can lead to reduction in the severity of disability and improve patient outcomes. The treatment window for IV Alteplase is within 3 hours of last known well (LKW) and up to 4.5 hours in certain eligible patients. Community education of the message “time is brain” is a critical component in the chain of survival for stroke patients. The American Heart Association and the American Stroke Association have focused community awareness efforts on signs & symptoms recognition and the importance of acting F.A.S.T. © when stroke symptoms occur. Our objective is to determine if ischemic stroke patients are arriving to the hospital within the timeframe to be eligible for IV Alteplase treatment. Methods: Get With the Guidelines (GWTG) -Stroke® is a quality improvement initiative to improve care by promoting adherence to scientific guidelines. A retrospective review was conducted of 337, 407 ischemic stroke patients from over 325 hospitals using GWTG-Stroke® in the Midwest from 2011 through 2016. LKW to hospital arrival times were analyzed. Results: The percentage of patients arriving within 3 hours of LKW was as follows: 23.3% in 2011, 22.5% in 2012, 23.1% in 2013, 22.5% in 2014, 23.4% in 2015, and 23.3% in 2016. The percentage of patients arriving within 4.5 hours of LKW: 29.1% in 2011, 28.2 % in 2012, 28.9% in 2013, 28.4% in 2014, 29.5% in 2015, 29.4% in 2016. Conclusions: Throughout the six years of this study, an average of only 23% of ischemic stroke patients arrived to the hospital within 3 hours of LKW, with slightly more, 29%, of patients arriving within the extended window (4.5 hrs of LKW) to be considered eligible for IV Alteplase treatment. With greater than 70% of patients arriving too late to receive this clot-busting drug, this data identifies the continued need for community education regarding acting F.A.S.T. © in recognizing signs and symptoms of stroke.

Intravenous Thrombolysis in Unknown-Onset Stroke: Results From the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry.

Stroke patients with unknown onset (UKO) are excluded from thrombolytic therapy. We aim to study the safety and efficacy of intravenous alteplase in ischemic stroke patients with UKO of symptoms compared with those treated within 4.5 hours in a large cohort. Data were analyzed from 47 237 patients with acute ischemic stroke receiving intravenous tissue-type plasminogen activator in hospitals participating in the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry between 2010 and 2014. Two groups were defined: (1) patients with UKO (n=502) and (2) patients treated within 4.5 hours of stroke onset (n=44 875). Outcome measures were symptomatic intracerebral hemorrhage per Safe Implementation of Treatment in Stroke on the 22 to 36 hours post-treatment neuroimaging and mortality and functional outcome assessed by the modified Rankin Scale at 3 months. Patients in UKO group were significantly older, had more severe stroke at baseline, and longer door-to-needle times than patients in the ≤4.5 hours group. Logistic regression showed similar risk of symptomatic intracerebral hemorrhage (adjusted odds ratio, 1.09; 95% confidence interval, 0.44-2.67) and no significant differences in functional independency (modified Rankin Scale score of 0-2; adjusted odds ratio, 0.79; 95% confidence interval, 0.56-1.10), but higher mortality (adjusted odds ratio, 1.58; 95% confidence interval, 1.04-2.41) in the UKO group compared with the ≤4.5 hours group. Patients treated within 4.5 hours showed reduced disability over the entire range of modified Rankin Scale compared with the UKO group (common adjusted odds ratio, 1.29; 95% confidence interval, 1.01-1.65). Our data suggest no excess risk of symptomatic intracerebral hemorrhage but increased mortality and reduced favorable outcome in patients with UKO stroke compared with patients treated within the approved time window.

Orolingual angioedema after thrombolysis is not associated with insular cortex ischemia on pre-thrombolysis CT

ObjectiveOrolingual angioedema (OA) is a well known early complication of treatment with alteplase in ischemic stroke patients. Our aim was to study risk factors for OA in these patients, namely insular cortex ischemia. MethodsRetrospective case-cohort study using the prospective registry of all consecutive ischemic stroke patients submitted to intravenous thrombolysis with alteplase. Clinical data was retrieved from the registry and medical records. Two independent observers evaluated early signs of insular cortex ischemia on pre-thrombolysis computed tomography (CT) and of insular cortex infarct on early follow-up imaging. Univariate and multivariate analysis were performed to identify predictors of OA. ResultsOf the 659 patients with acute ischemic stroke treated with alteplase, 32 developed OA (4.9%, 95%CI=3.3–6.6). Frequency of early signs of insular cortex ischemia on pre-thrombolysis CT and of insular cortex infarct on follow-up imaging was similar in patients with and without OA (p=0.241 and p=0.145, respectively). The only independent predictors of OA occurrence were female sex (OR=5.47, 95%CI=1.98–15.10) and angiotensin-converting enzyme inhibitor (ACE-I) use (OR=3.87, 95%CI=1.71–8.75). ConclusionsFemale sex and ACE-I use are independent risk factors for OA occurrence in ischemic stroke patients treated with alteplase. Early signs of insular cortex ischemia on pre-thrombolysis CT were not significantly associated with OA.

Intravenous Alteplase in Ischemic Stroke Patients not Fully Adhering to the Current Drug License in Central and Eastern Europe

The current European license for alteplase in acute ischemic stroke excludes from treatment large groups of patients. Nevertheless, in everyday practice, many patients receive off-label thrombolysis at the physician's discretion. Our aim was to evaluate safety and effectiveness of intravenous alteplase in patients not fully adhering to the drug license compared with those treated strictly according to the license in Central and Eastern Europe. We analyzed the data contributed to Safe Implementation of Thrombolysis in Stroke registry from nine countries between February 2003 and February 2010. Statistical analysis included multivariate logistic regression. Of 5594 consecutive patients, 1919 patients (34·3%) not fully adhered to the license. The most frequent deviations were: time-to-treatment >3 h (13·1%), use of intravenous antihypertensives (8·3%), age >80 years (7·3%), oral anticoagulation (4·2%), a previous stroke with concomitant diabetes (3·9%), and previous stroke <three-months (2·7%). The off-label group showed a significantly higher rate of symptomatic intracranial haemorrhage, which was not confirmed in the multivariate analysis. License nonadherence significantly increased the risk of death or dependency (odds ratio 1·26; 95% confidence interval: 1·08-1·48), with a trend for increased mortality (odds ratio 1·17; 95% confidence interval: 0·97-1·42). Isolated time-to-treatment >3 h was an independent predictor of unfavorable outcome (odds ratio 1·32; 95% confidence interval: 1·01-1·71). Our findings show that patients not fully adhering to the European license are not at increased risk of symptomatic intracranial haemorrhage but achieve less favorable outcome. Some contraindications appear more redundant than others. However, the final conclusions about safety and effectiveness should be based on the results of ongoing randomized trials.