Dataset Information

Association of Time From Stroke Onset to Groin Puncture With Quality of Reperfusion After Mechanical Thrombectomy: A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials.

ABSTRACT:

Importance

Reperfusion is a key factor for clinical outcome in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) for large-vessel intracranial occlusion. However, data are scarce on the association between the time from onset and reperfusion results.

Objective

To analyze the rate of reperfusion after EVT started at different intervals after symptom onset in patients with AIS.

Design, setting, and participants

We conducted a meta-analysis of individual patient data from 7 randomized trials of the Highly Effective Reperfusion Using Multiple Endovascular Devices (HERMES) group. This is a multicenter cohort study of the intervention arm of randomized clinical trials included in the HERMES group. Patients with anterior circulation AIS who underwent EVT for M1/M2 or intracranial carotid artery occlusion were included. Each trial enrolled patients according to its specific inclusion and exclusion criteria. Data on patients eligible but not enrolled (eg, refusals or exclusions) were not available. All analyses were performed by the HERMES biostatistical core laboratory using the pooled database. Data were analyzed between December 2010 and April 2015.

Main outcomes and measures

Successful reperfusion was defined as a modified thrombolysis in cerebral infarction score of 2b/3 at the end of the EVT procedure adjusted for age, occlusion location, pretreatment intravenous thrombolysis, and clot burden score and was analyzed in relation to different intervals (onset, emergency department arrival, imaging, and puncture) using mixed-methods logistic regression.

Results

Among the 728 included patients, with a mean (SD) age of 65.4 (13.5) years and of whom 345 were female (47.4%), decreases in rates of successful reperfusion defined as a thrombolysis in cerebral infarction score of 2b/3 were observed with increasing time from admission or first imaging to groin puncture. The magnitude of effect was a 22% relative reduction (odds ratio, 0.78; 95% CI, 0.64-0.95) per additional hour between admission and puncture and a 26% relative reduction (odds ratio, 0.74; 95% CI, 0.59-0.93) per additional hour between imaging and puncture.

Conclusions and relevance

Because the probability of reperfusion declined significantly with time between hospital arrival and groin puncture, we provide additional arguments for minimizing the intervals after symptom onset in anterior circulation acute ischemic stroke.

SUBMITTER: Bourcier R

PROVIDER: S-EPMC6459219 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and purposePost hoc analyses of randomized controlled clinical trials evaluating mechanical thrombectomy have suggested that admission-to-groin-puncture (ATG) delays are associated with reduced reperfusion rates. Purpose of this analysis was to validate this association in a real-world cohort and to find associated factors and confounders for prolonged ATG intervals.MethodsPatients included into the BEYOND-SWIFT cohort (Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the Solitaire FR With the Intention for Thrombectomy; https://www.clinicaltrials.gov; Unique identifier: NCT03496064) were analyzed (n=2386). Association between baseline characteristics and ATG was evaluated using mixed linear regression analysis. The effect of increasing symptom-onset-to-admission and ATG intervals on successful reperfusion (defined as Thrombolysis in Cerebral Infarction [TICI] 2b-3) was evaluated using logistic regression analysis adjusting for potential confounders.ResultsMedian ATG was 73 minutes. Prolonged ATG intervals were associated with the use of magnetic resonance imaging (+19.1 [95% CI, +9.1 to +29.1] minutes), general anesthesia (+12.1 [95% CI, +3.7 to +20.4] minutes), and borderline indication criteria, such as lower National Institutes of Health Stroke Scale, late presentations, or not meeting top-tier early time window eligibility criteria (+13.8 [95% CI, +6.1 to +21.6] minutes). There was a 13% relative odds reduction for TICI 2b-3 (adjusted odds ratio [aOR], 0.87 [95% CI, 0.79-0.96]) and TICI 2c/3 (aOR, 0.87 [95% CI, 0.79-0.95]) per hour ATG delay, while the reduction of TICI 2b-3 per hour increase symptom-onset-to-admission was minor (aOR, 0.97 [95% CI, 0.94-0.99]) and inconsistent regarding TICI 2c/3 (aOR, 0.99 [95% CI, 0.97-1.02]). After adjusting for identified factors associated with prolonged ATG intervals, the association of ATG delay and lower rates of TICI 2b-3 remained tangible (aOR, 0.87 [95% CI, 0.76-0.99]).ConclusionsThere is a great potential to reduce ATG, and potential targets for improvement can be deduced from observational data. The association between in-hospital delay and reduced reperfusion rates is evident in real-world clinical data, underscoring the need to optimize in-hospital workflows. Given the only minor association between symptom-onset-to-admission intervals and reperfusion rates, the causal relationship of this association warrants further research. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03496064.

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 purposeAlthough current guidelines advocate pretreatment with intravenous thrombolysis (IVT) in all eligible patients with acute ischemic stroke with large-vessel occlusion before mechanical thrombectomy, there are observational data questioning the efficacy of this approach. One of the main arguments in favor of IVT pretreatment is the potential for tissue-type plasminogen activator-induced successful reperfusion (SR) before the onset of endovascular procedure.MethodsWe performed a systematic review and meta-analysis of randomized controlled clinical trials and observational cohorts providing rates of SR with IVT in patients with large-vessel occlusion before the initiation of mechanical thrombectomy. We also performed subgroup analyses according to study type (randomized controlled clinical trials versus observational) and according to the inclusion per protocol of patients with tandem (intracranial/extracranial) occlusions.ResultsWe identified 13 eligible studies (7 randomized controlled clinical trials and 6 observational cohorts), including 1561 patients with acute ischemic stroke (median National Institutes of Health Stroke Scale score, 17) with large-vessel occlusion. SR following IVT and before mechanical thrombectomy was documented in 11% (95% confidence interval, 7%-16%), with no difference among cohorts derived from randomized controlled clinical trials and observational studies. There was significant heterogeneity across included studies both in the overall analysis and among subgroups (I2>84%; P for Cochran Q, <0.001). Higher tissue-type plasminogen activator-induced SR rates were documented in studies reporting the exclusion of tandem occlusions (17%; 95% confidence interval, 11%-23%) compared with the rest (7%; 95% confidence interval, 4%-11%; P for subgroup differences, 0.003).ConclusionsPretreatment with systemic thrombolysis in patients with large-vessel occlusion eligible for mechanical thrombectomy results in SR in 1 of 10 cases, negating the need for additional endovascular reperfusion. Tandem occlusions seem to be the least responsive to IVT pretreatment.