Intravenous Alteplase For Acute Stroke Research Articles

Endovascular thrombectomy with or without intravenous alteplase in acute stroke: a systematic review and meta-analysis of randomized clinical trials.

This study investigated clinical outcomes after direct endovascular thrombectomy (EVT) compared to bridging therapy (EVT with prior intravenous alteplase) in acute stroke within 4.5h after onset. PubMed and Embase were searched for eligible randomized controlled trials. The primary outcome was the rates of neurological functional independence defined as modified Rankin scale score 0-2 at 90days, whose non-inferiority margin was set at - 15%, - 10%, - 6.5%, - 5%, and - 1.3% for its risk difference (RD). We included six studies enrolling 2334 participants. The crude cumulative rates of functional independence were 49.0% with direct EVT vs 50.9% with bridging therapy, without significant difference (Odd ratio [OR] = 0.93, 95% confidence interval [CI] 0.79-1.09) between two groups, where the pooled RD was - 2% (95% CI - 6 to 2%) whose lower 95% CI bound fell within non-inferiority margins of - 15%, - 10%, -6.5%, but not - 5% and - 1.3%. Between the two groups, no significant difference was found in excellent function rate (30.2% vs 30.6%, OR = 0.99, 95% CI 0.82-1.18) with RD of 0% (95% CI - 3 to 4%), mortality rate (16.0% vs 15.0%, OR = 1.08, 95% CI 0.86-1.35) with RD of 1% (95% CI - 2 to 4%), and symptomatic intracranial hemorrhage rate (4.3% vs 5.0%, OR = 0.86, 95% CI 0.58-1.27) with RD of 0% (95% CI - 2 to 1%). No statistical difference was found in functional and safety outcomes between direct EVT and bridging therapy groups in acute stroke within 4.5h after symptom onset. EVT alone was non-inferior to bridging therapy for several, but not the more stringent, non-inferiority margins.

In ischemic stroke, thrombectomy alone was noninferior to thrombectomy plus alteplase for functional outcome at 90 days.

Yang P, Zhang Y, Zhang L, et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. N Engl J Med. 2020;382:1981-93. 32374959.

Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke

BackgroundIn acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy.MethodsWe conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area.ResultsOf 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P=0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group.ConclusionsIn Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People’s Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.)

Time to recanalization and risk of symptomatic intracerebral haemorrhage in patients treated with intravenous thrombolysis

To test whether time to recanalization is associated with a progressive risk of symptomatic intracerebral haemorrhage (SICH) after intravenous alteplase (IVT), we conducted a serial transcranial duplex monitoring study up to 24 h after IVT in a cohort of 140 patients with acute ischaemic stroke attributed to large artery occlusion in the anterior circulation. Patients were classified in four groups according to the time to complete recanalization (Thrombolysis in Brain Ischaemia, TIBI grades 4 or 5) after alteplase bolus: <2 h (n = 53), 2-6 h (n = 9), 6-24 h (n = 32) and no recanalization (NR) at 24 h (n = 46). SICH was defined as any haemorrhagic transformation with National Institute of Health Stroke Scale (NIHSS) score worsening ≥ 4 points (European Australian Acute Stroke Study II, ECASS II criteria) or parenchymal haematoma type 2 with neurological worsening (SITS-MOST criteria) in the 24-36 h CT. Favourable outcome was defined as modified Rankin score ≤ 2 at 3 months. There were no differences between the groups of patients who recanalized at each time frame regarding localization of the occlusion (P = 0.29), stroke severity at baseline (P = 0.22) and age (P = 0.06). SICH (ECASS/SITS-MOST) was observed in 5.7%/5.7% of the patients who recanalized in <2 h, in 0%/0% of the patients who recanalized between 2-6 h, in 3.1%/3.1% of the patients who recanalized within 6-24 h and in 2.2%/0% of those patients who did not recanalize at 24 h. The rate of favourable outcome according to the time of recanalization was 79.2%, 50%, 46.9% and 34.1% (P < 0.001). Our findings are in line with the literature showing a relationship between time to recanalization and functional outcome after IVT in acute stroke, but they do not confirm a progressive increase in the rate of SICH.

Thrombolytic therapy for acute stroke in Austria: data from the Safe Implementation of Thrombolysis in Stroke (SITS) register

We aimed at determining the safety and efficacy of IV alteplase in Austrian versus non-Austrian centres as documented in the Internet-based registers Safe Implementation of Thrombolysis for Stroke - MOnitoring STudy (SITS-MOST) and - International Stroke Thrombolysis Register (SITS-ISTR). We analysed patient data entered in the registers SITS-MOST and SITS-ISTR in the period December 2002 to 15 November 2007. Compared to the non-Austrian cohort (n=15153), the Austrian cohort (n=896) was slightly older [median, interquartile range (IQR): 70, 60-77 years vs. 69, 60-76 years, P=0.05] and included more women (44.6% vs. 41.0%, P=0.03). Austrian patients had a significantly shorter stroke onset-to-treatment time (OTT; median, IQR: 135, 105-160 min vs. 145, 115-170 min, P<0.0005). Symptomatic intracerebral haemorrhages were observed in 1.6% of Austrian and 1.7% of non-Austrian patients (P=0.82). At 3 months, 50.8% of Austrian and 53.0% of non-Austrian patients were independent (P=0.23), but death was less frequent in Austrian patients (12.1% vs. 14.9%, P=0.03). Multivariate analyses adjusted for demographic and baseline characteristics confirmed lower mortality at 3 months in the Austrian cohort (odds ratio 0.81, 95% confidence intervals 0.71-0.92, P=0.001). Longer OTT was associated with increased mortality at 3 months, with a hazard ratio of 1.02 (95% CI 1.01-1.03; P=0.005) for each 10-min increase in OTT. The implementation of intravenous alteplase for acute stroke has been safe and efficacious in Austrian centres. OTT and mortality were significantly lower in Austrian patients compared to non-Austrian SITS centres.

Thrombolysis with 0.6 mg/kg intravenous alteplase for acute stroke in routine clinical practice: the outline of Japan post-Marketing Alteplase Registry Study (J-MARS)

Thrombolysis with 0.6 mg/kg intravenous alteplase for acute stroke in routine clinical practice: the outline of Japan post-Marketing Alteplase Registry Study (J-MARS)