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Desmoteplase for Acute Ischemic Stroke within 3 to 9?Hours after Symptom Onset: Evidence from Randomized Controlled Trials.

ABSTRACT: Recent studies have shown inconsistent results regarding the value of desmoteplase for treating acute ischemic stroke (AIS) when administered within an extended time window. We performed a meta-analysis to explore the value of desmoteplase in AIS treatment. The MEDLINE, EMBASE, and Cochrane Library databases were searched for randomized controlled trials (RCTs) that had evaluated desmoteplase versus placebo for AIS. The primary outcomes were intracranial hemorrhage (ICH) within 72?hours and favorable outcome at Day 90. We pooled 819 patients from 5 RCTs. Desmoteplase treatment showed a neutral effect on favorable outcome (P?=?0.42) but a favorable safety profile in terms of ICH (P?=?0.64) compared with the placebo group. In the subgroup analysis, 90??g/kg desmoteplase, a late time to treatment (6-9?hours), and serious stroke symptoms at baseline (NIHSS?>?12) subgroups showed high risks of ICH (P???0.02). A high dose of desmoteplase (125??g/kg) showed a tendency to improve recanalization (P?=?0.05), but was also associated with an increased risk of death (P?=?0.04). In conclusion, desmoteplase administered over an extended time window had no significant effect on functional recovery but exhibited a favorable safety profile in patients with AIS.

SUBMITTER: Shi L

PROVIDER: S-EPMC5037417 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Desmoteplase for Acute Ischemic Stroke within 3 to 9 Hours after Symptom Onset: Evidence from Randomized Controlled Trials.

Shi Ligen L Liang Feng F Li Yunping Y Shao Anwen A Zhou Keren K Yu Jun J Zhang Jianmin J

Scientific reports 20160927

Recent studies have shown inconsistent results regarding the value of desmoteplase for treating acute ischemic stroke (AIS) when administered within an extended time window. We performed a meta-analysis to explore the value of desmoteplase in AIS treatment. The MEDLINE, EMBASE, and Cochrane Library databases were searched for randomized controlled trials (RCTs) that had evaluated desmoteplase versus placebo for AIS. The primary outcomes were intracranial hemorrhage (ICH) within 72 hours and favo ...[more]

PMID: 27671010

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Project description:BackgroundThe optimal dose of tenecteplase vs. alteplase for acute ischemic stroke (AIS) has yet to be established. Therefore, we included the latest randomized controlled trials (RCT) to assess the efficacy and safety of different doses of tenecteplase vs. alteplase for AIS within 4.5 hours of symptom onset.MethodsLiterature was searched in PubMed, Cochrane Library, Embase, Web of Science, and clinical trial registries until February 12, 2023. Odds ratios (OR) with 95% credible intervals (CrI) were estimated using Bayesian network meta-analysis (NMA). Treatments were ranked based on efficacy and safety using the surface under the cumulative ranking curve (SUCRA).ResultsEleven RCTs with 5,475 patients were included. Tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg had significantly higher rates of excellent functional outcome (tenecteplase: OR, 1.85; 95% CrI, 1.44-2.37; alteplase: OR, 1.60; 95% CrI, 1.29-1.97) and good functional outcome (tenecteplase: OR, 1.54; 95% CrI, 1.19-1.98; alteplase: OR, 1.40; 95% CrI, 1.14-1.74) than placebo, despite an increased risk of symptomatic intracranial hemorrhage. Furthermore, the NMA (OR, 1.16; 95% CrI, 1.01-1.33) and the pairwise meta-analysis (OR, 1.16; 95% CI, 1.02-1.33; P = 0.03) indicated that tenecteplase 0.25 mg/kg was superior to alteplase 0.9 mg/kg in excellent functional outcome. Alteplase 0.9 mg/kg (OR, 2.54; 95% CrI, 1.45-8.08) significantly increased the risk of any intracranial hemorrhage compared with placebo. SUCRA results demonstrated that tenecteplase 0.25 mg/kg ranked first and tenecteplase 0.4 mg/kg ranked last in efficacy outcomes.ConclusionsThe NMA indicated that tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg are safe and significantly improve clinical outcomes in patients with AIS within 4.5 h of symptom onset. Furthermore, tenecteplase 0.25 mg/kg provides more benefit and has the potential to replace alteplase 0.9 mg/kg in AIS treatment.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/index.php, identifier: CRD42022343948.

Project description:ImportanceTwo 2018 randomized controlled trials (DAWN and DEFUSE 3) demonstrated the clinical benefit of mechanical thrombectomy (MT) more than 6 hours after onset in acute ischemic stroke (AIS). Health-economic evidence is needed to determine whether the short-term health benefits of late MT translate to a cost-effective option during a lifetime in the United States.ObjectiveTo compare the cost-effectiveness of 2 strategies (MT added to standard medical care [SMC] vs SMC alone) for various subgroups of patients with AIS receiving care more than 6 hours after symptom onset.Design, setting, and participantsThis economic evaluation study used the results of the DAWN and DEFUSE 3 trials to populate a cost-effectiveness model from a US health care perspective combining a decision tree and Markov trace. The DAWN and DEFUSE 3 trials enrolled 206 international patients from 2014 to 2017 and 182 US patients from 2016 to 2017, respectively. Patients were followed until 3 months after stroke. The clinical outcome at 3 months was available for 29 subgroups of patients with AIS and anterior circulation large vessel occlusions. Data analysis was conducted from July 2018 to October 2019.ExposuresMT with SMC in the extended treatment window vs SMC alone.Main outcomes and measuresExpected costs and quality-adjusted life-years (QALYs) during lifetime were estimated. Deterministic results (incremental costs and effectiveness, incremental cost-effectiveness ratios, and net monetary benefit) were presented, and probabilistic analyses were performed for the total populations and 27 patient subgroups.ResultsIn the DAWN study, the MT group had a mean (SD) age of 69.4 (14.1) years and 42 of 107 (39.3%) were men, and the control group had a mean (SD) age of 70.7 (13.2) years and 51 of 99 (51.5%) were men. In the DEFUSE 3 study, the MT group had a median (interquartile range) age of 70 (59-79) years, and 46 of 92 (50.0%) were men, and the control group had a median (interquartile range) age of 71 (59-80) years, and 44 of 90 (48.9%) were men. For the total trial population, incremental cost-effectiveness ratios were $662/QALY and $13 877/QALY based on the DAWN and DEFUSE 3 trials, respectively. MT with SMC beyond 6 hours had a probability greater than 99.9% of being cost-effective vs SMC alone at a willingness-to-pay threshold of $100 000/QALY. Subgroup analyses showed a wide range of probabilities for MT with SMC to be cost-effective at a willingness-to-pay threshold of $50 000/QALY, with the greatest uncertainty observed for patients with a National Institute of Health Stroke Scale score of at least 16 and for those aged 80 years or older.Conclusions and relevanceThe results of this study suggest that late MT added to SMC is cost-effective in all subgroups evaluated in the DAWN and DEFUSE 3 trials, with most results being robust in probabilistic sensitivity analyses. Future MT evidence-gathering could focus on older patients and those with National Institute of Health Stroke Scale scores of 16 and greater.

Project description:Background and purposePrompt thrombolytic therapy with intravenous alteplase reduces disability after acute ischemic stroke. In an exploratory analysis, we examined whether long-term survival varied by baseline characteristics after alteplase.MethodsIn this open-treatment, international, randomized, controlled trial, ischemic stroke patients were randomly allocated <6 hours of onset to intravenous alteplase (0.9 mg/kg) plus standard care (n=1515) or standard care alone (n=1520). We followed patients to death, censoring when last known to be alive. We grouped patients by delay to randomization, and good or poor predicted prognosis (calculated from baseline National Institutes of Health Stroke Scale [NIHSS] score and age). We present absolute mortality differences between treated and control groups at 7 days, 6 months, and 18 months poststroke.ResultsAlteplase was not associated with a significant increase in mortality within 18 months (0.6% [95% confidence interval (CI), -2.9% to +4.2] P=0.72] in all patients with complete vital status (99.9%, 3034/3035). In patients randomized <3 hours of stroke, 18-month mortality was lower in the alteplase-treated group than the control group (40.6% [95% CI, 42.6-52.7] versus 47.8% [95% CI, 35.5-45.3]; P=0.0434]. The difference in 18-month mortality between alteplase-treated and control patients was greater in patients who were randomized early (<3 hours) compared with late (3-6 hours; +9% [95% CI, 1-17]; P=0.0317). Alteplase led to a greater improvement in 18-month survival in patients with a poor prognosis than in patients with a good prognosis (+8% [95% CI, 2-14]; P=0.0091).ConclusionsThese exploratory analyses of the third International Stroke Trial (IST-3) trial support improving acute stroke patients' access to earlier alteplase treatment, treatment of patients with poor prognosis, and further randomized controlled trials in minor stroke to replicate these findings.Clinical trial registration urlhttp://www.controlled-trials.com. Unique identifier: ISRCTN25765518.

Project description:BACKGROUND:In acute ischemic stroke, blood pressure (BP) tends to rise initially and fall to a baseline level within 24-48 hours. Previous studies reported several different effects of BPs during acute ischemic stroke on clinical outcomes, which was partly due to the different time intervals from stroke onset to BP measurement. METHODS:All patients with acute ischemic stroke (onset ≤3 hours) who lived independently before the stroke, were consecutively enrolled for a 62-month period. BPs at 0, 12, and 24 hours after admission were collected. A favorable outcome was defined as a modified Rankin Scale (mRS) score 0-2 at discharge. For different standards of BP management, patients were grouped and analyzed according to intravenous (IV) tissue plasminogen activator (tPA) treatment and favorable outcome. RESULTS:Among the 446 enrolled patients, 227 patients underwent IV tPA treatment and 216 had mRS score 0-2 at discharge. Patients with favorable outcomes had lower initial NIH Stroke Scale (NIHSS) scores, less frequent progressive neurological deficits, and lower systolic BP (SBP) 12 and 24 hours after admission than patients with unfavorable outcomes, regardless of whether they underwent tPA treatment or not (p <0.05). The BP decreased over a period of 24 hours after admission. In logistic regression analysis, the independent variables associated with favorable outcome were the initial NIHSS score, a progressive neurological deficit, a previous stroke, and the SBP 24 hours after admission in the patients who underwent tPA treatment and the initial NIHSS score and a progressive neurological deficit in the patients who did not undergo tPA treatment (p <0.05). CONCLUSIONS:The SBPs at 12 and 24 hours after admission were lower in acute stroke patients with favorable outcomes than in the other patients, regardless of whether the patients underwent tPA therapy and the SBP at 24 hours was an independent predictor of favorable outcomes among the patients who underwent tPA treatment.

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Desmoteplase for Acute Ischemic Stroke within 3 to 9?Hours after Symptom Onset: Evidence from Randomized Controlled Trials.

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Desmoteplase for Acute Ischemic Stroke within 3 to 9 Hours after Symptom Onset: Evidence from Randomized Controlled Trials.

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