scholarly journals Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke

Stroke ◽  
2019 ◽  
Vol 50 (8) ◽  
pp. 2156-2162 ◽  
Author(s):  
Adrian M. Burgos ◽  
Jeffrey L. Saver

Background and Purpose— TNK (tenecteplase), a newer fibrinolytic agent, has practical delivery advantages over ALT (alteplase) that would make it a useful agent if noninferior in acute ischemic stroke treatment outcome. Accordingly, the most recent US American Heart Association/American Stroke Association acute ischemic stroke guideline recognized TNK as an alternative to ALT, but only based on informal consideration, rather than formal meta-analysis, of completed randomized control trials. Methods— Systematic literature search and formal meta-analysis were conducted per PRISMA guidelines (Preferred Reporting Items for Systemic Reviews and Meta-Analyses), adapted to noninferiority analysis. The primary outcome of freedom from disability (modified Rankin Scale score, 0–1) outcome at 3 m, and additional efficacy and safety outcomes, were analyzed. Results— Systematic search identified 5 trials enrolling 1585 patients (828 TNK, 757 ALT). Across all trials, mean age was 70.8, 58.5% male, baseline National Institutes of Health Stroke Scale mean 7.0, and time from last known well to treatment start mean 148 minutes. All ALT patients received standard 0.9 mg/kg dosing, while TNK dosing was 0.1 mg/kg in 6.8%, 0.25 mg/kg in 24.6%, and 0.4 mg/kg in 68.6%. For the primary end point, crude cumulative rates of disability-free (modified Rankin Scale score, 0–1) 3 m outcome were TNK 57.9% versus ALT 55.4%. Informal, random-effects meta-analysis, the risk difference was 4% (95% CI, −1% to 8%). The lower 95% CI bound fell well within the prespecified noninferiority margin. Similar results were seen for the additional efficacy end points: functional independence (modified Rankin Scale score, 0–2): crude TNK 71.9% versus ALT 70.5%, risk difference 2% (95% CI, −3% to 6%); and modified Rankin Scale shift analysis, common odds ratio 1.21 (95% CI, 0.93–1.57). For safety end points, lower event rates reduced power, but point estimates were also consistent with noninferiority Conclusions— Accumulated clinical trial data provides strong evidence that TNK is noninferior to ALT in the treatment of acute ischemic stroke. These findings provide formal support for the recent guideline recommendation to consider TNK an alternative to ALT.

2021 ◽  
pp. neurintsurg-2021-017667
Author(s):  
Chun-Hsien Lin ◽  
Jeffrey L Saver ◽  
Bruce Ovbiagele ◽  
Wen-Yi Huang ◽  
Meng Lee

ObjectiveTo conduct a meta-analysis of randomized trials to comprehensively compare the effect of endovascular thrombectomy (EVT) versus intravenous thrombolysis (IVT) plus EVT on functional independence (modified Rankin Scale (mRS) 0–2) after acute ischemic stroke due to large vessel occlusions (AIS-LVO).MethodsWe searched Pubmed, EMBASE, CENTRAL, and clinicaltrials.gov from January 2000 to February 2021 and abstracts presented at the International Stroke Conference in March 2021 to identify trials comparing EVT alone versus IVT plus EVT in AIS-LVO. Five non-inferiority margins established in the literature were assessed: −15%, −10%, −6.5%, −5%, and −1.3% for the risk difference for functional independence at 90 days.ResultsFour trials met the selection criteria, enrolling 1633 individuals, with 817 participants randomly assigned to EVT alone and 816 to IVT plus EVT. Crude cumulative rates of 90-day functional independence were 46.0% with EVT alone versus 45.5% with IVT plus EVT. Pooled results showed the risk difference of functional independence was 1% (95% CI −4% to 5%) between EVT alone versus IVT plus EVT. The lower 95% CI bound of −4% fell within the non-inferiority margins of −15%, −10%, −6.5%, and −5%, but not −1.3%. Pooled results also showed the risk difference between EVT alone versus IVT plus EVT was 1% (95% CI −3% to 5%) for mRS 0–1, and 1% (95% CI −1% to 3%) for symptomatic intracranial hemorrhage.ConclusionsThis meta-analysis suggests that EVT alone is non-inferior to IVT plus EVT for several, but not the most stringent, non-inferiority margins.


Stroke ◽  
2020 ◽  
Vol 51 (11) ◽  
pp. 3232-3240 ◽  
Author(s):  
Johanna M. Ospel ◽  
Bijoy K. Menon ◽  
Andrew M. Demchuk ◽  
Mohammed A. Almekhlafi ◽  
Nima Kashani ◽  
...  

Background and Purpose: Available data on the clinical course of patients with acute ischemic stroke due to medium vessel occlusion (MeVO) are mostly limited to those with M2 segment occlusions. Outcomes are generally better compared with more proximal occlusions, but many patients will still suffer from severe morbidity. We aimed to determine the clinical course of acute ischemic stroke due to MeVO with and without intravenous alteplase treatment. Methods: Patients with MeVO (M2/M3/A2/A3/P2/P3 occlusion) from the INTERRSeCT (The Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) and PRoveIT (Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy) studies were included. Baseline characteristics and clinical outcomes were summarized using descriptive statistics. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days, describing excellent functional outcome. Secondary outcomes were the common odds ratio for a 1-point shift across the modified Rankin Scale and functional independence, defined as modified Rankin Scale score of 0 to 2. We compared outcomes between patients with versus without intravenous alteplase treatment and between patients who did and did not show recanalization on follow-up computed tomography angiography. Logistic regression was used to provide adjusted effect-size estimates. Results: Among 258 patients with MeVO, the median baseline National Institutes of Health Stroke Scale score was 7 (interquartile range: 5–12). A total of 72.1% (186/258) patients were treated with intravenous alteplase and in 41.8% (84/201), recanalization of the occlusion (revised arterial occlusive lesion score 2b/3) was seen on follow-up computed tomography angiography. Excellent functional outcome was achieved by 50.0% (129/258), and 67.4% (174/258) patients gained functional independence, while 8.9% (23/258) patients died within 90 days. Recanalization was observed in 21.4% (9/42) patients who were not treated with alteplase and 47.2% (75/159) patients treated with alteplase ( P =0.003). Early recanalization (adjusted odds ratio, 2.29 [95% CI, 1.23–4.28]) was significantly associated with excellent functional outcome, while intravenous alteplase was not (adjusted odds ratio, 1.70 [95% CI, 0.88–3.25]). Conclusions: One of every 2 patients with MeVO did not achieve excellent clinical outcome at 90 days with best medical management. Early recanalization was strongly associated with excellent outcome but occurred in <50% of patients despite intravenous alteplase treatment.


Author(s):  
Ganesh Asaithambi ◽  
Amy L Castle ◽  
Emily H Marino ◽  
Bridget M Ho ◽  
Sandra K Hanson

Background: It has been suggested that there is a “weekend effect” resulting in higher mortality rates for stroke patients admitted on weekends. We examine this phenomenon for acute ischemic stroke (AIS) patients presenting to telestroke (TS) sites to determine its effect on stroke code process times and outcomes. Methods: From October 2015-June 2017, we reviewed consecutive AIS patients receiving IV alteplase within our TS network who then were transferred to our CSC. We compared patients presenting to TS sites on weekdays (Monday 0700 to Friday 1859) to patients presenting on weekends (Friday 1900 to Monday 0659). We analyzed door to code activation, code activation to TS evaluation, door to imaging, and door to needle times. Rates of favorable outcome (modified Rankin Scale score ≤2) and death at 90 days were compared. Results: We identified 89 (54 weekday, 35 weekend) patients (mean age 71.8±13.3 years, 47.2% women) during the study period. Median door to code activation (15 [5, 27] vs 8 [1, 17] mins, p=0.01) and door to needle (61 [49, 73] vs 47 [35, 59] mins, p=0.003) times were significantly longer for patients presenting on weekends compared to weekdays. There were no significant differences in median door to imaging (weekend 17 [7, 30] vs weekday 11 [6, 21], p=0.1) and code activation to TS evaluation (weekend 7 [6, 10] vs weekday 5 [4, 9], p=0.14) times. The rates of favorable outcome (weekend 50% vs weekday 66.7%, p=0.18) and death (weekend 8.3% vs weekday 4.8%, p=0.56) at 90 days were not significantly different. Conclusion: While there were no significant differences in outcomes, the “weekend effect” results in slower door to code activation and door to needle times. Efforts to improve methods in increasing efficiency of care on weekends should be considered.


2016 ◽  
Vol 5 (3-4) ◽  
pp. 118-122 ◽  
Author(s):  
Marie L. Schmitz ◽  
Sharon D. Yeatts ◽  
Thomas A. Tomsick ◽  
David S. Liebeskind ◽  
Achala Vagal ◽  
...  

Background: Prompt revascularization is the main goal of acute ischemic stroke treatment. We examined which revascularization scale - reperfusion (modified Treatment in Cerebral Infarctions, mTICI) or recanalization (Arterial Occlusive Lesion, AOL) - better predicted the clinical outcome in ischemic stroke participants treated with endovascular therapy (EVT). Additionally, we determined the optimal thresholds for the predictive accuracy of each scale. Methods: We included participants from the Interventional Management of Stroke (IMS) III trial with complete occlusion in the internal carotid artery terminus or proximal middle cerebral artery (M1 or M2) who completed EVT within 7 h of symptom onset. The abilities of the AOL and mTICI scales to predict a favorable outcome (defined as a modified Rankin Scale score of 0-2 at 3 months) were compared by receiver operating characteristic analyses. The maximal sensitivity and specificity for each revascularization scale were established. Results: Among 240 participants who met the study inclusion criteria, 79 (33%) achieved a favorable outcome. Higher scores of mTICI and AOL increased the likelihood of a favorable outcome (2.7% with mTICI 0 vs. 83.3% with mTICI 3, and 3.0% with AOL 0 vs. 43% with AOL 3). The accuracy of mTICI reperfusion and AOL recanalization for a favorable outcome prediction was similar, with optimal thresholds of mTICI 2b/3 and AOL 3, respectively. Conclusion: Reperfusion (mTICI) and recanalization (AOL) predicted a favorable clinical outcome with comparable accuracy in ischemic stroke participants treated with EVT. Optimal revascularization goals to maximize clinical outcome (modified Rankin Scale score of 0-2) consisted of complete recanalization (AOL 3) and reperfusion of at least 50% of the arterial tree of the symptomatic artery (mTICI 2b/3) in the IMS III trial setting.


2021 ◽  
pp. 174749302110473
Author(s):  
Jin Pyeong Jeon ◽  
Chih-Hao Chen ◽  
Fon-Yih Tsuang ◽  
Jianming Liu ◽  
Michael D Hill ◽  
...  

Background. The impact of renal impairment (RI) on the outcomes of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) was relatively limited and contradictory. We performed a systematic review and meta-analysis to investigate this. Aims. We registered a protocol on September 2020 and searched MEDLINE, EMBASE, and Google Scholar accordingly. RI was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Predefined outcomes included functional independence (defined as a modified Rankin Scale of 0, 1, or 2) at 3 months, successful reperfusion, mortality, and symptomatic intracerebral hemorrhage (sICH). Summary of review. Eleven studies involving 3453 patients were included. For the unadjusted outcomes, RI was associated with fewer functional independence (odds ratio (OR), 0.49; 95% confidence interval (CI), 0.39–0.62) and higher mortality (OR, 2.55; 95% CI, 2.03–3.21). RI was not associated with successful reperfusion (OR, 0.80; 95% CI 0.63–1.00) and sICH (OR, 1.41; 95% CI, 0.95–2.10). For the adjusted outcomes, results derived from a multivariate meta-analysis were consistent with the respective unadjusted outcomes: functional independence (OR, 0.59; 95% CI, 0.45–0.77), mortality (OR, 2.23, 95% CI, 1.45–3.43), and sICH (OR, 1.34; 95% CI, 0.85–2.10). Conclusions. We presented the first systematic review to demonstrate that RI is associated with fewer functional independence and higher mortality. Future EVT studies should publish complete renal eGFR data to facilitate prognostic studies and permit eGFR to be analyzed in a continuous variable. Systematic Review Registration: PROSPERO CRD42020191309


Author(s):  
Azalea T. Pajo ◽  
Jose Danilo B. Diestro ◽  
Adrian I. Espiritu ◽  
Adam A. Dmytriw ◽  
Alejandro Enriquez-Marulanda ◽  
...  

ABSTRACT:Background:Intravenous tissue-type plasminogen activator (IVtPA) is a proven treatment for acute ischemic stroke; however, diabetes mellitus (DM) and previous cerebral infarction (PCI) were considered relative contraindications for thrombolysis within the 3–4.5 h period.Objective:The study aimed to determine the safety and efficacy of IVtPA among diabetic patients with PCI presenting with acute ischemic stroke.Methods:Studies which evaluated the outcome of IVtPA in terms of symptomatic intracerebral hemorrhage (sICH), functional outcome in modified Rankin scale, and death among diabetic patients with PCI presenting with acute ischemic stroke within the 3–4.5 h period were systematically searched until July 2019. Screening and eligibility criteria were applied. Risk of bias was evaluated using the Newcastle–Ottawa Scale. Odds ratios (ORs) with 95% confidence interval (CI) were used to compare measures of treatment effect. Mantel–Haenszel method and random-effects model were also employed.Results:Four registry-based studies with a total of 44,572 patients were included for quantitative synthesis. Giving IVtPA among DM+/PCI+ patients did not result in significantly increased rate of sICH (OR, 1.09; 95% CI, 0.88, 1.36) compared to No DM+/PCI+ patients. However, there was significantly higher mortality (OR, 1.81; 95% CI, 1.60, 2.06) in the DM+/PCI+ group. Conversely, among those who survived, the DM+/PCI+ patients were more functionally independent at 3 months (OR, 0.76; 95% CI, 0.61, 0.94).Conclusion:Limited evidence suggests that thrombolysis in DM+/PCI+ patients does not result in significantly higher incidence of sICH and may improve functional independence. However, the significantly higher mortality in this group warrants an assessment of the individualized risk–benefit ratio in the use of IVtPA.


Stroke ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 923-930 ◽  
Author(s):  
Esmee Venema ◽  
Adrien E. Groot ◽  
Hester F. Lingsma ◽  
Wouter Hinsenveld ◽  
Kilian M. Treurniet ◽  
...  

Background and Purpose— To assess the effect of inter-hospital transfer on time to treatment and functional outcome after endovascular treatment (EVT) for acute ischemic stroke, we compared patients transferred from a primary stroke center to patients directly admitted to an intervention center in a large nationwide registry. Methods— MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry is an ongoing, prospective, observational study in all centers that perform EVT in the Netherlands. We included adult patients with an acute anterior circulation stroke who received EVT between March 2014 to June 2016. Primary outcome was time from arrival at the first hospital to arterial groin puncture. Secondary outcomes included the 90-day modified Rankin Scale score and functional independence (modified Rankin Scale score of 0–2). Results— In total 821/1526 patients, (54%) were transferred from a primary stroke center. Transferred patients less often had prestroke disability (227/800 [28%] versus 255/699 [36%]; P =0.02) and more often received intravenous thrombolytics (659/819 [81%] versus 511/704 [73%]; P <0.01). Time from first presentation to groin puncture was longer for transferred patients (164 versus 104 minutes; P <0.01, adjusted delay 57 minutes [95% CI, 51–62]). Transferred patients had worse functional outcome (adjusted common OR, 0.75 [95% CI, 0.62–0.90]) and less often achieved functional independence (244/720 [34%] versus 289/681 [42%], absolute risk difference −8.5% [95% CI, −8.7 to −8.3]). Conclusions— Interhospital transfer of patients with acute ischemic stroke is associated with delay of EVT and worse outcomes in routine clinical practice, even in a country where between-center distances are short. Direct transportation of patients potentially eligible for EVT to an intervention center may improve functional outcome.


2019 ◽  
Vol 10 (2) ◽  
pp. 115-117
Author(s):  
Ganesh Asaithambi ◽  
Amy L. Castle ◽  
Megan E. Tipps ◽  
Bridget M. Ho ◽  
Emily H. Marino ◽  
...  

A “weekend effect” resulting in higher mortality rates for patients with stroke admitted on weekends has been reported. We examine this phenomenon for patients with acute ischemic stroke (AIS) presenting to telestroke (TS) sites to determine its effect on stroke alert process times and outcomes. From October 2015 to June 2017, we reviewed patients with AIS receiving intravenous alteplase within our TS network. We compared patients presenting to TS sites on weekdays (Monday 07:00 to Friday 18:59) to those presenting on weekends (Friday 19:00 to Monday 06:59). We analyzed door-to-alert activation, alert activation-to-TS evaluation, door-to-imaging, and door-to-needle times. Rates of favorable outcome (modified Rankin Scale score ≤2) and death at 90 days were compared. We identified 89 (54 weekday and 35 weekend) patients (mean age: 71.8 ± 13.3 years, 47.2% women) during the study period. Median door-to-alert activation ( P = .01) and door-to-needle ( P = .004) times were significantly longer for patients presenting on weekends compared to weekdays. There were no significant differences in median door-to-imaging ( P = .1) and alert activation-to-TS evaluation ( P = .07) times. Rates of favorable outcome ( P = .19) and death ( P = .56) at 90 days did not differ. While there were no significant differences in outcomes, patients presenting on weekends had longer door-to-alert activation and door-to-needle times. Efforts to improve methods in efficiency of care on weekends should be considered.


Stroke ◽  
2021 ◽  
Vol 52 (1) ◽  
pp. 144-151
Author(s):  
Zuolu Liu ◽  
Nerses Sanossian ◽  
Sidney Starkman ◽  
Gilda Avila-Rinek ◽  
Marc Eckstein ◽  
...  

Background and Purpose: A survival advantage among individuals with higher body mass index (BMI) has been observed for diverse acute illnesses, including stroke, and termed the obesity paradox. However, prior ischemic stroke studies have generally tested only for linear rather than nonlinear relations between body mass and outcome, and few studies have investigated poststroke functional outcomes in addition to mortality. Methods: We analyzed consecutive patients with acute ischemic stroke enrolled in a 60-center acute treatment trial, the NIH FAST-MAG acute stroke trial. Outcomes at 3 months analyzed were (1) death; (2) disability or death (modified Rankin Scale score, 2–6); and (3) low stroke-related quality of life (Stroke Impact Scale<median). Relations with BMI were analyzed univariately and in multivariate models adjusting for 14 additional prognostic variables. Results: Among 1033 patients with acute ischemic stroke, average age was 71 years (±13), 45.1% female, National Institutes of Health Stroke Scale 10.6 (±8.3), and BMI 27.5 (±5.6). In both unadjusted and adjusted analysis, increasing BMI was linearly associated with improved 3-month survival ( P =0.01) odds ratios in adjusted analysis for mortality declined across the BMI categories of underweight (odds ratio, 1.7 [CI, 0.6–4.9]), normal (odds ratio, 1), overweight (0.9 [CI, 0.5–1.4]), obese (0.5, [CI, 0.3–1.0]), and severely obese (0.4 [CI, 0.2–0.9]). In unadjusted analysis, increasing BMI showed a U-shaped relation to poststroke disability or death (modified Rankin Scale score, 2–6), with odds ratios of modified Rankin Scale score, 2 to 6 for underweight, overweight, and obese declined initially when compared with normal weight patients, but then increased again in severely obese patients, suggesting a U-shaped or J-shaped relation. After adjustment, including for baseline National Institutes of Health Stroke Scale, modified Rankin Scale score 2 to 6 was no longer related to adiposity. Conclusions: Mortality and functional outcomes after acute ischemic stroke have disparate relations with patients’ adiposity. Higher BMI is linearly associated with increased survival; and BMI has a U-shaped or J-shaped relation to disability and stroke-related quality of life. Potential mechanisms including nutritional reserve aiding survival during recovery and greater frequency of atherosclerotic than thromboembolic infarcts in individuals with higher BMI.


Stroke ◽  
2021 ◽  
Author(s):  
Mouhammad A. Jumaa ◽  
Alicia C. Castonguay ◽  
Hisham Salahuddin ◽  
Ashutosh P. Jadhav ◽  
Kaustubh Limaye ◽  
...  

Background and Purpose: The safety and benefit of mechanical thrombectomy in the treatment of acute ischemic stroke patients with M2 segment middle cerebral artery occlusions remain uncertain. Here, we compare clinical and angiographic outcomes in M2 versus M1 occlusions in the STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) Registry. Methods: The STRATIS Registry was a prospective, multicenter, nonrandomized, observational study of acute ischemic stroke large vessel occlusion patients treated with the Solitaire stent-retriever as the first-choice therapy within 8 hours from symptoms onset. Primary outcome was defined as functional disability at 3 months measured by dichotomized modified Rankin Scale. Secondary outcomes included reperfusion rates and rates of symptomatic intracranial hemorrhage. Results: A total of 984 patients were included, of which 538 (54.7%) had M1 and 170 (17.3%) had M2 occlusions. Baseline demographics were well balanced within the groups, with the exception of mean baseline National Institutes of Health Stroke Scale score which was significantly higher in the M1 population (17.3±5.5 versus 15.7±5.0, P ≤0.001). No difference was seen in mean puncture to revascularization times between the cohorts (46.0±27.8 versus 45.1±29.5 minutes, P =0.75). Rates of successful reperfusion (modified Thrombolysis in Cerebral Infarction≥2b) were similar between the groups (91% versus 95%, P =0.09). M2 patients had significantly increased rates of symptomatic ICH at 24 hours (4% versus 1%, P =0.01). Rates of good functional outcome (modified Rankin Scale score of 0–2; 58% versus 59%, P =0.83) and mortality (15% versus 14%, P =0.75) were similar between the 2 groups. There was no difference in the association of outcome and onset to groin puncture or onset to successful reperfusion in M1 and M2 occlusions. Conclusions: In the STRATIS Registry, M2 occlusions achieved similar rates of successful reperfusion, good functional outcome, and mortality, although increased rates of symptomatic ICH were demonstrated when compared with M1 occlusions. The time dependence of benefit was also similar between the 2 groups. Further studies are needed to understand the benefit of mechanical thrombectomy for M2 occlusions. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02239640.


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