scholarly journals Lipid-Lowering Pretreatment and Outcome Following Intravenous Thrombolysis for Acute Ischaemic Stroke: A Post Hoc Analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study Trial

2018 ◽  
Vol 45 (5-6) ◽  
pp. 213-220 ◽  
Author(s):  
Jatinder S. Minhas ◽  
Xia Wang ◽  
Hisatomi Arima ◽  
Philip M. Bath ◽  
Laurent Billot ◽  
...  

Background: Debate exists as to whether statin pretreatment confers an increased risk of 90-day mortality and symptomatic intracranial haemorrhage (sICH) in acute ischaemic stroke (AIS) patients treated with intravenous thrombolysis. We assessed the effects of undifferentiated lipid-lowering pretreatment on outcomes and interaction with low-dose versus standard-dose alteplase in a post hoc subgroup ­analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study. Methods: In all, 3,284 thrombolysis-eligible AIS patients (mean age 66.6 years; 38% women), with information on lipid-lowering pretreatment, were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 h of symptom onset. Of the total number of patients, 615 (19%) received statin or other lipid-lowering pretreatment. The primary clinical outcome was combined endpoint of death or disability (modified Rankin Scale scores 2–6) at 90 days. Results: Compared with patients with no lipid-lowering pretreatment, those with lipid-lowering pretreatment were significantly older, more likely to be non-Asian and more likely to have a medical history including vascular co-morbidity. After propensity analysis assessment and adjustment for important baseline variables at the time of randomisation, as well as imbalances in management during the first 7 days of hospital admission, there were no significant differences in mortality (OR 0.85; 95% CI 0.58–1.25, p = 0.42), or in overall ­90-day death and disability (OR 0.85, 95% CI 0.67–1.09, p = 0.19), despite a significant decrease in sICH among those with ­lipid-lowering pretreatment according to the European Co-operative Acute Stroke Study 2 definition (OR 0.49, 95% CI 0.28–0.83, p = 0.009). No differences in key efficacy or safety outcomes were seen in patients with and without lipid-lowering pretreatment between low- and standard-dose alteplase arms. Conclusions: Lipid-lowering pretreatment is not associated with adverse outcome in AIS patients treated with intravenous alteplase, whether assessed by 90-day death and disability or death alone.

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Xia Wang ◽  
Thompson Robinson ◽  
Hisatomi. Arima ◽  
Joseph Broderick ◽  
Andrew Demchuk ◽  
...  

Background and Purpose: As lower doses of alteplase reduce the risk of symptomatic intracerebral hemorrhage (sICH), older and Asian people may benefit more from low-dose alteplase than other patients with acute ischemic stroke (AIS). Methods: Data from the ENhanced Control of Hypertension ANd Thrombolysis strokE study (ENCHANTED), an international, multi-center, prospective, randomized, open-label, blinded-endpoint trial, were analyzed to assess effects of low- (0.6mg/kg body weight) vs. standard-dose (0.9mg/kg) alteplase in AIS patients, by age and ethnicity (Asian vs. non-Asian), pre-specified subgroup analyses, on key efficacy and safety outcomes. Results: 3297 patients (1248 female), mean age 67 years were included. After adjusting for baseline characteristics and management variables over the first seven days, increasing age was associated with poor outcome, defined by ordinal analysis of the modified Rankin score (mRS) (shift to a less favorable outcome, P trend <0.0001). In the comparison between low- and standard-dose alteplase, no significant differences were observed for 90-day poor outcome by age deciles and ethnicity. Less sICH was observed with low-dose alteplase, and this was consistent for age and ethnicity. There was no ethnic difference in the treatment effects by age, severity, and time to treatment. Conclusions: Increasing age predicts poor outcome in thrombolysis-treated AIS patients. There was no heterogeneity in the treatment effects of low- vs. standard-dose alteplase. Decisions about intravenous thrombolysis should be based on variables other than age and ethnicity.


2017 ◽  
Vol 2 (2) ◽  
pp. 53-58 ◽  
Author(s):  
Lily Song ◽  
Xia Wang ◽  
Thompson Robinson ◽  
Richard I Lindley ◽  
Hisatomi Arima ◽  
...  

BackgroundThe characteristics of patients with acute ischaemic stroke (AIS) and their management vary across regions, which may influence outcomes. We examined for differential patterns of outcome between China and non-China participants of the ENhanced Control of Hypertension And Thrombolysis strokE stuDy (ENCHANTED), which tested different alteplase doses in AIS.MethodsENCHANTED was an international, multicentre, open, blinded-endpoint trial of the effects of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase on 90-day disability outcomes and symptomatic intracerebral haemorrhage (sICH) in 3310 patients with AIS.ResultsParticipants (n=1419, 48%) in China were younger, and more often male, hypertensive and with prior stroke and coronary artery disease, but less likely to have atrial fibrillation and use antihypertensive, antithrombotic and lipid-lowering agents, compared with non-China patients with AIS. Although China participants had more AIS due to large artery occlusion, were treated later and had differing ancillary management, there was no significant difference in 90-day modified Rankin scale scores 2–6 (55.6% vs 47.8%; OR, adjusted for baseline and management factors 0.87 (95% CI 0.71 to 1.07; p=0.20)) and risk of sICH (Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria: 1.4% vs 1.8%; p=0.12) compared with non-China participants. There was no heterogeneity in the treatment effects of low-dose versus standard-dose alteplase between China and non-China participants.ConclusionPatients with AIS recruited to the ENCHANTED trial in China had similar outcomes in response to thrombolysis treatment despite significantly differing demographic, clinical and management factors to patients with AIS in other regions.


2018 ◽  
Vol 3 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Xia Wang ◽  
Shoujiang You ◽  
Shoichiro Sato ◽  
Jie Yang ◽  
Cheryl Carcel ◽  
...  

The optimal dose of recombinant tissue plasminogen activator (rtPA) for acute ischaemic stroke (AIS) remains controversial, especially in Asian countries. We aimed to update the evidence regarding the use of low-dose versus standard-dose rtPA. We performed a systematic literature search across MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to 22 August 2016 to identify all related studies. The outcomes were death or disability (defined by modified Rankin Scale 2–6), death, and symptomatic intracerebral haemorrhage (sICH). Where possible, data were pooled for meta-analysis with ORs and corresponding 95% CIs by means of random-effects or fixed-effects meta-analysis. We included 26 observational studies and 1 randomised controlled trial with a total of 23 210 patients. Variable doses of rtPA were used for thrombolysis of AIS in Asia. Meta-analysis shows that low-dose rtPA was not associated with increased risk of death or disability (OR 1.13, 95% CI 0.95 to 1.33), or death (OR 0.86, 95% CI 0.74 to 1.01), or decreased risk of sICH (OR 1.06, 95% CI 0.65 to 1.72). The results remained consistent when sensitivity analyses were performed including only low-dose and standard-dose rtPA or only Asian studies. Our review shows small difference between the outcomes or the risk profile in the studies using low-dose and/or standard-dose rtPA for AIS. Low-dose rtPA was not associated with lower risk of death or disability, death alone, or sICH.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chaohua Cui ◽  
Yanbo Li ◽  
Jiajia Bao ◽  
Shuju Dong ◽  
Lijie Gao ◽  
...  

Abstract Background For acute ischaemic stroke patients, it is uncertain whether intravenous thrombolysis combined with statins might increase the therapeutic effect. Additionally, using high-intensity statins after thrombolysis may increase the risk of bleeding in patients. Asian stroke patients often take low-dose statins. It is speculated that reducing the dose of statins may improve the risk of bleeding. Methods Data from consecutive acute ischaemic stroke patients with intravenous thrombolysis were prospectively collected. Efficacy outcomes included NIHSS (National Institutes of Health Stroke Scale) score improvement at 7 days after admission and mRS (Modified Rankin Scale) improvement at 90 days. Safety outcomes included haemorrhage events (intracerebral haemorrhage and gastrointestinal haemorrhage) in the hospital and death events within 2 years. Results The study finally included 215 patients. The statin group had a higher percentage of NIHSS improvement at 7 days (p < 0.001) and a higher percentage of a favourable functional outcome (FFO, mRS <  = 2) (p < 0.001) at 90 days. The statin group had a lower percentage of intracerebral haemorrhage (p < 0.001) and gastrointestinal haemorrhage (p = 0.003) in the hospital and a lower percentage of death events (p < 0.001) within 2 years. Logistic regression indicated that statin use was significantly related to NIHSS improvement (OR = 4.697, p < 0.001), a lower percentage of intracerebral haemorrhage (OR = 0.372, p = 0.049) and gastrointestinal haemorrhage (OR = 0.023, p = 0.016), and a lower percentage of death events (OR = 0.072, p < 0.001). Conclusion For acute ischaemic stroke patients after intravenous thrombolysis, the use of low-dose statins was related to NIHSS improvement at 7 days and inversely related to haemorrhage events in the hospital and death events within 2 years, especially for moderate stroke or noncardioembolic stroke patients.


2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Xuya Huang ◽  
Phillip Nash ◽  
Vafa Alakbarzade ◽  
Brian Clarke ◽  
Anthony C. Pereira

Intravenous thrombolysis with alteplase within 4.5 hours from symptom onset is a well-established treatment of acute ischaemic stroke (AIS). The aim was to compare alteplase for AIS between patients aged >80 and ≤80 years in our registry data, from 2013 to 2018. Mechanical thrombectomy cases were excluded. We assessed clinical outcomes over the six-year period and between patients aged over 80 and ≤80 years, using measures including the discharge modified Rankin Scale (mRS), 24-hour National Institutes of Health Stroke Scale (NIHSS) improvement, and symptomatic intracerebral haemorrhage (sICH) rate. Of a total of 805 AIS patients who received intravenous alteplase, 278 (34.5%) were over 80 years old, and 527 (65%) were younger. 616 (76.5%) received thrombolysis ≤ 3 hours after symptom onset and 189 (23.5%) within 3-4.5 hours. Median baseline mRS and NIHSS of the elderly cohort were 1 (IQR 0-5) and 13 (IQR 2-37), respectively, compared to the younger cohort 0 (IQR 0-5) and 9 (IQR 0-29). The sICH rate was 7.2% in the elderly and 4.6% in those ≤80 years, p = 0.05 . NIHSS improved within 24 hours in 34% of the elderly cohort compared to 35% in the younger cohort. At hospital discharge, the mortality rate was 9% in the elderly cohort compared to the 6% in the younger cohort, p = 0.154 . 25% of patients aged >80 years had mRS ≤ 2 compared to 47% in the younger patients ( p < 0.0001 ). In conclusion, thrombolysis in elderly patients results in clinical improvement comparable to younger patients.


2020 ◽  
Vol 5 (3) ◽  
pp. 285-290
Author(s):  
Huaguang Zheng ◽  
Yi Yang ◽  
Huisheng Chen ◽  
Chuanling Li ◽  
Yangkun Chen ◽  
...  

Background and purposeData on the efficacy and safety of alteplase for acute ischaemic stroke (AIS) administered 3–4.5 hours after the onset of stroke symptoms in Chinese patients is limited. We sought to determine whether AIS patients would benefit from thrombolysis with alteplase between 3 and 4.5 hours after the onset of stroke symptoms in a prospective, multicentre, single-arm trial in China.Materials and methodsEligible AIS patients were given 0.9 mg/kg alteplase intravenously. The primary efficacy endpoint was a favourable outcome at 3 months, defined as a score of 0 or 1 on the modified Rankin Scale. Thresholds for the primary efficacy endpoint were determined to be 40% based on the literature review. The primary safety endpoint was symptomatic intracranial haemorrhage (sICH) according to the European Cooperative Acute Stroke Study III (ECASS III) trial definition. Post hoc analysis between this study and the ECASS III trial were compared using the propensity score matching (PSM) method.ResultsA total of 120 eligible AIS patients from 11 sites in China received thrombolysis therapy in this study. The median time from onset of symptoms to needle was 3 hours 54 min. The percentage of patients with a favourable outcome was 63.3% (95% CI 54.4 to 71.4), significantly higher than the predefined threshold (p<0.0001). Three patients (2.5%, 95% CI 0.5 to 7.1) had sICH, including two fatal sICH. Six patients died within 3 months after treatment. The post hoc PSM analysis showed a numerically higher rate of the primary efficacy endpoint in this study (63.3%) than the matched placebo arm (56.7%) in the ECASS III trial.ConclusionsIntravenous alteplase with a standard dose administered between 3 and 4.5 hours after onset of symptoms is effective and safe for Chinese AIS patients.Trial registration numberNCT02930837


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Zien Zhou ◽  
Candice Delcourt ◽  
Chao Xia ◽  
Sohei Yoshimura ◽  
Cheryl Carcel ◽  
...  

Objective: To identify any differential efficacy and safety of low- versus standard-dose intravenous alteplase for lacunar versus non-lacunar acute ischemic stroke (AIS) in the alteplase dose-arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: In a cohort of 3297 ENCHANTED participants, we identified those with lacunar or non-lacunar AIS with different levels of confidence (definite/probable/possible) according to pre-specified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration [END] or death) and treatment effects of low- versus standard-dose alteplase across lacunar and non-lacunar AIS with adjustment for baseline covariables. Results: Of 2588 participants with available imaging and clinical data, we classified cases as definite or probable lacunar (n=490) or non-lacunar AIS (n=2098) for primary analyses. Regardless of the alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% CI] 0.60 [0.47-0.77]) and other clinical or safety outcomes, compared to participants with non-lacunar AIS. Overall, low-dose alteplase (compared to standard) had no differential effect on the functional outcome (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of ICH. There were no differential treatment effects of low- versus standard-dose alteplase on all outcomes across lacunar and non-lacunar AIS (all P interaction ≥0.07). Conclusions: We found no clear evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard-dose for definite/probable lacunar AIS.


2019 ◽  
Vol 48 (3-6) ◽  
pp. 207-216
Author(s):  
Xia Wang ◽  
Lili Song ◽  
Jie Yang ◽  
Lingli Sun ◽  
Tom J. Moullaali ◽  
...  

Objective: To determine the extent to which the effects of intensive blood pressure (BP) lowering are modified by doses of alteplase in thrombolysis-eligible acute ischemic stroke (AIS) patients. Methods: Prespecified analyses of the Enhanced Control of Hypertension and Thrombolysis Stroke Study for patients enrolled in both arms: (i) low-dose (0.6 mg/kg body weight) or standard-dose (0.9 mg/kg) alteplase and (ii) intensive (target systolic BP [SBP] 130–140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) BP management. The primary outcome was functional recovery, measured by a shift in scores on modified Rankin scale at 90 days. The safety outcome was any intracranial hemorrhage (ICH). Results: There were 925 participants (mean age 67 years, 39% female, 77% Asian) randomized to both arms: 242 randomly assigned to guideline/standard-dose (GS); 234 to guideline/low-dose (GL); 227 to intensive/standard-dose (IS); and 222 to intensive/low-dose (IL). Overall, average SBP levels within 24 h were lower in the low-dose compared to standard-dose alteplase group (146 and 144 vs. 151 and 150 mm Hg, for GS and GL vs. IS and IL, respectively, p < 0.0001). There was no heterogeneity of the effects of BP lowering (intensive vs. guideline) on functional recovery between standard-dose (OR 0.81, 95% CI 0.59–1.12) and low-dose alteplase (1.06, 0.77–1.47; p = 0.25 for interaction). Similar results were observed for ICH (p = 0.50 for interaction). Conclusions: In thrombolysis-treated patients with predominantly mild-to-moderate severity AIS, intensive BP lowering neither improve functional recovery, either with low- or standard-dose intravenous alteplase, nor beneficially interact with low-dose alteplase in reducing ICH. Trial Registration: The trial is registered with ClinicalTrials.gov (NCT01422616).


Neurology ◽  
2021 ◽  
Vol 96 (11) ◽  
pp. e1512-e1526
Author(s):  
Zien Zhou ◽  
Candice Delcourt ◽  
Chao Xia ◽  
Sohei Yoshimura ◽  
Cheryl Carcel ◽  
...  

ObjectiveTo determine any differential efficacy and safety of low- vs standard-dose IV alteplase for lacunar vs nonlacunar acute ischemic stroke (AIS), we performed post hoc analyzes from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) alteplase dose arm.MethodsIn a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence (definite/according to prespecified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin Scale [mRS] scores 2–6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration or death) and treatment effects of low- vs standard-dose alteplase across lacunar and nonlacunar AIS with adjustment for baseline covariables.ResultsOf 2,588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n = 490) or nonlacunar AIS (n = 2,098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2–6, adjusted odds ratio [95% confidence interval] 0.60 [0.47–0.77]) and other clinical or safety outcomes compared to participants with nonlacunar AIS. Low-dose alteplase (versus standard) had no differential effect on functional outcomes (mRS 2–6, 1.04 [0.87–1.24]) but reduced the risk of symptomatic ICH in all included participants. There were no differential treatment effects of low- vs standard-dose alteplase on all outcomes across lacunar and nonlacunar AIS (all pinteraction ≥0.07).ConclusionsWe found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/probable lacunar AIS.Classification of EvidenceThis study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safety over standard-dose alteplase.Clinical Trial RegistrationClinicaltrials.gov identifier NCT01422616.


VASA ◽  
2017 ◽  
Vol 46 (2) ◽  
pp. 116-120 ◽  
Author(s):  
Naz Ahmed ◽  
Damian Kelleher ◽  
Manmohan Madan ◽  
Sarita Sochart ◽  
George A. Antoniou

Abstract. Background: Insufficient evidence exists to support the safety of carotid endarterectomy (CEA) following intravenous thrombolysis (IVT) for acute ischaemic stroke. Our study aimed to report a single-centre experience of patients treated over a five-year period. Patients and methods: Departmental computerised databases were interrogated to identify patients who suffered an ischaemic stroke and subsequently underwent thrombolysis followed by CEA. Mortality and stroke within 30 days of surgery were defined as the primary outcome end points. Results: Over a five-year period, 177 out of a total of 679 carotid endarterectomies (26 %) were performed in patients presenting with acute ischaemic stroke. Twenty-five patients (14 %) received IVT prior to CEA in the form of alteplase. Sixty percent of patients were male with a mean age of 68 years. Sixteen patients (64 %) underwent CEA within 14 days of IVT and the median interval between thrombolysis and CEA was 7.5 days (range, 3–50 days). One female patient died of a further intraoperative stroke within 30 days of surgery, yielding a mortality rate of 4 %. Two patients (8 %) suffered from cardiac complications postoperatively resulting in a short high dependency unit stay. Another two patients (8 %) developed local wound complications, which were managed conservatively without the need for re-operation. The median hospital length of stay was 4.5 days (range, 1–33 days). Conclusions: Our experience indicates that CEA post-thrombolysis has a low incidence of mortality. Further high quality evidence is required before CEA can be routinely recommended following IVT for acute ischaemic stroke.


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