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Meta-analysis using individual participant data (IPD-MA) from randomized controlled trials (RCTs) can strengthen evidence used for decision making and is considered the "gold standard" approach. In this study, we present the importance, properties, and main approaches of conducting an IPD-MA. We exemplify the main approaches of conducting an IPD-MA and how these can be used to obtain subgroup effects through estimation of interaction terms. IPD-MA has several benefits over traditional aggregate data (AD) meta-analysis. These include standardization of definitions of outcomes and/or scales, reanalysis of eligible RCTs using the same analysis model across all studies, accounting for missing outcome data, detecting outliers, using participant-level covariates to explore intervention-by-covariate interactions, and tailoring intervention effects to participant characteristics. IPD-MA can be performed in either a 2-stage or 1-stage approach. We exemplify the presented methods using 2 illustrative examples. The first real-life example includes 6 studies assessing sonothrombolysis with or without addition of microspheres against IV thrombolysis alone (i.e., control) in acute ischemic stroke participants with large vessel occlusions. The second real-life example includes 7 studies evaluating the association between blood pressure levels after endovascular thrombectomy and functional improvement of acute ischemic stroke in patients with large vessel occlusion. IPD reviews can be associated with higher quality statistical analysis and may differ from AD reviews. Unlike individual trials that lack power and AD meta-analysis results, which suffer from confounding and aggregation bias, the use of IPD allows us to explore intervention-by-covariate interactions. However, a key limitation of conducting an IPD-MA is retrieval of IPD from original RCTs. Time and resources should be carefully planned before embarking on retrieving IPD., (© 2023 American Academy of Neurology.)

Background and Objectives: To explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of patients with acute ischemic stroke (AIS) patients with large vessel occlusion (LVO)., Methods: A study was eligible if it enrolled patients with AIS >18 years of age with an LVO treated with either successful or unsuccessful EVT and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed with a generalized linear mixed-effects model., Results: A total of 5,874 patients (mean age 69 ± 14 years; 50% women; median NIH Stroke Scale score on admission 16) from 7 published studies were included. Increasing mean systolic BP levels per 10 mm Hg during the first 24 hours after the end of the EVT were associated with a lower odds of functional improvement (unadjusted common odds ratio [OR] 0.82, 95% confidence interval [CI] 0.80-0.85; adjusted common OR 0.88, 95% CI 0.84-0.93) and modified Rankin Scale score ≤2 (unadjusted OR 0.82, 95% CI 0.79-0.85; adjusted OR 0.87, 95% CI 0.82-0.93) and a higher odds of all-cause mortality (unadjusted OR 1.18, 95% CI 1.13-1.24; adjusted OR 1.15, 95% CI 1.06-1.23) at 3 months. Higher 24-hour mean systolic BP levels were also associated with an increased likelihood of early neurologic deterioration (unadjusted OR 1.14, 95% CI 1.07-1.21; adjusted OR 1.14, 95% CI 1.03-1.24) and a higher odds of symptomatic intracranial hemorrhage (unadjusted OR 1.20, 95% CI 1.09-1.29; adjusted OR 1.20, 95% CI 1.03-1.38) after EVT., Discussion: Increased mean systolic BP levels in the first 24 hours after EVT are independently associated with a higher odds of symptomatic intracranial hemorrhage, early neurologic deterioration, 3-month mortality, and worse 3-month functional outcomes., (© 2021 American Academy of Neurology.)

Background and Purpose: Evidence about the utility of ultrasound-enhanced thrombolysis (sonothrombolysis) in patients with acute ischemic stroke (AIS) is conflicting. We aimed to evaluate the safety and efficacy of sonothrombolysis in patients with AIS with large vessel occlusion, by analyzing individual patient data of available randomized-controlled clinical trials., Methods: We included all available randomized-controlled clinical trials comparing sonothrombolysis with or without addition of microspheres (treatment group) to intravenous thrombolysis alone (control group) in patients with AIS with large vessel occlusion. The primary outcome measure was the rate of complete recanalization at 1 to 36 hours following intravenous thrombolysis initiation. We present crude odds ratios (ORs) and ORs adjusted for the predefined variables of age, sex, baseline stroke severity, systolic blood pressure, and onset-to-treatment time., Results: We included 7 randomized controlled clinical trials that enrolled 1102 patients with AIS. A total of 138 and 134 confirmed large vessel occlusion patients were randomized to treatment and control groups respectively. Patients randomized to sonothrombolysis had increased odds of complete recanalization compared with patients receiving intravenous thrombolysis alone (40.3% versus 22.4%; OR, 2.17 [95% CI, 1.03-4.54]; adjusted OR, 2.33 [95% CI, 1.02-5.34]). The likelihood of symptomatic intracranial hemorrhage was not significantly different between the 2 groups (7.3% versus 3.7%; OR, 2.03 [95% CI, 0.68-6.11]; adjusted OR, 2.55 [95% CI, 0.76-8.52]). No differences in the likelihood of asymptomatic intracranial hemorrhage, 3-month favorable functional and 3-month functional independence were documented., Conclusions: Sonothrombolysis was associated with a nearly 2-fold increase in the odds of complete recanalization compared with intravenous thrombolysis alone in patients with AIS with large vessel occlusions. Further study of the safety and efficacy of sonothrombolysis is warranted.