Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 7 appraisals
Lancet (London, England)
Ticagrelor with aspirin dual antiplatelet therapy combined with intravenous thrombolysis in patients with ischaemic stroke in China (TAPIS): a multicentre, double-blind, randomised controlled trial
BACKGROUND: Evidence supporting the early addition of antiplatelet therapy to intravenous thrombolysis in patients with acute ischaemic stroke remains inconclusive. We aimed to investigate the efficacy and safety of early oral dual antiplatelet therapy (DAPT), started within 6 h of onset, as an adjunct to intravenous thrombolysis. METHODS: TAPIS was a randomised, double-blind, placebo-controlled trial done in 60 hospitals across China. We enrolled patients treated with intravenous thrombolysis for ischaemic stroke, with a National Institutes of Health Stroke Scale score of 4-10. We randomly assigned (1:1) patients to receive oral aspirin plus ticagrelor (DAPT group) or corresponding placebo within 6 h of stroke onset, either before, during, or after receiving thrombolysis. Ticagrelor or placebo was continued for days 2-7 in each group, with open-label aspirin administered for days 2-90. Patients, clinicians, and investigators were masked to the group assignment. The primary efficacy outcome was an excellent functional outcome (modified Rankin Scale score 0-1) at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage within 36 h. This trial was registered with ClinicalTrials.gov (NCT06316570) and is completed. FINDINGS: Between April 3, 2024, and Sept 30, 2025, we randomly assigned 1382 patients to the early DAPT (n=690 [49·9%]) or placebo (n=692 [50·1%]) groups. The median age was 65·6 years (IQR 58·3-72·0), 991 (71·7%) were men, and 391 (28·3%) were women. At 90 days, 474 (68·7%) patients in the early DAPT group and 429 (62·0%) in the placebo group achieved excellent functional outcomes (risk ratio 1·11 [95% CI 1·03-1·20; p=0·0089). Symptomatic intracranial haemorrhage within 36 h occurred in six (0·9%) patients in the early DAPT group versus five (0·7%) in the control group (risk ratio 1·20 [95% CI 0·37-3·93; p=0.76). INTERPRETATION: Among patients treated with intravenous thrombolysis for moderate ischaemic stroke, initiation of oral DAPT within 6 h of onset improved the likelihood of excellent functional outcomes at 90 days. Although no significant between-group difference in symptomatic intracranial haemorrhage was detected, wide CIs precluded exclusion of a small increased risk. FUNDING: National Natural Science Foundation of China, Capital's Funds for Health Improvement and Research, Noncommunicable Chronic Diseases-National Science and Technology Major Project, Beijing Municipal Science & Technology Commission, and the New Cornerstone Science Foundation.
18 May 2026
Read appraisal →Journal of neurointerventional surgery
Comparative safety and efficacy of invasive therapies for carotid artery stenosis: a systematic review and network meta-analysis
BACKGROUND: Carotid artery stenosis is a major cause of stroke and is commonly treated with carotid endarterectomy (CEA) or carotid artery stenting (CAS). Trans-carotid artery revascularization (TCAR) has emerged as a newer alternative designed to reduce the risk of procedural stroke. However, comparative evidence on the safety and efficacy of these interventions is limited. This study evaluates the clinical outcomes of CEA, CAS, and TCAR in patients with carotid artery stenosis. METHODS: A comprehensive search of multiple databases was conducted to identify relevant studies. The outcomes were stroke, mortality, and myocardial infarction, cranial nerve injury, hematoma, infection, transient ischemic attack, and length of hospital stay. Meta-analysis and a frequentist graph-theoretical approach network meta-analysis were performed using the netmeta package in R platform. Risk of bias was assessed using RoB 2 Cochrane and ROBINS-I. RESULTS: Fifty-five studies were included in the review. The short-term stroke risk was significantly lower with CEA than with CAS. TCAR had a potential long-term mortality benefit over CAS, while no significant differences were observed in short-term mortality or myocardial infarction across treatments. CAS was associated with lower risks of cranial nerve injury, hematoma, and infection compared with CEA. CONCLUSION: CEA and TCAR offer better short-term stroke protection than CAS, with TCAR showing promise for long-term mortality benefits. CAS has advantages in reducing cranial nerve injury, hematoma, and infection risks. Overall, the choice of treatment should consider both efficacy and safety profiles. Further high-quality randomized controlled trials, particularly focusing on TCAR, are needed to validate these comparative outcomes. PROSPERO REGISTRY NUMBER: CRD420251055287.
16 May 2026
Read appraisal →Journal of neurointerventional surgery
Intravascular lithotripsy in calcified carotid stenosis: technical and clinical outcomes
INTRODUCTION: Carotid artery stenosis (CAS) is a major cause of stroke, disability, and mortality worldwide. While medical therapy and revascularization remain the cornerstones of management, both surgical and endovascular approaches can be limited by complex anatomy and heavily calcified plaques, which increase procedural risk. Intravascular lithotripsy (IVL), originally developed for coronary and peripheral interventions, has recently emerged as a potential strategy for plaque modification in CAS. By delivering localized shockwave pulses, IVL fractures vascular calcium, facilitating safer angioplasty and stent deployment. However, its use in CAS remains off-label and poorly described. METHODS: A systematic search of PubMed, Google Scholar, and Embase was conducted in September 2025 in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies included patients with CAS undergoing IVL with reported procedural success and/or clinical outcomes. Risk of bias was assessed using the Joanna Briggs Institute (JBI) appraisal tools. RESULTS: Fifteen studies comprising 120 patients were included. The mean age ranged from 50 to 82 years, and the degree of stenosis from 70%-95%. Technical success was reported in 100% of cases. Across the pooled cohort, 101 of 120 patients (84.2%) achieved residual stenosis ≤30%. Seven patients (5.8%) experienced ipsilateral stroke or transient ischemic attack within 30 days. CONCLUSION: IVL for CAS is an emerging therapy demonstrating consistent technical feasibility and favorable short-term safety across published studies. These findings suggest that IVL may benefit patients with complex calcified plaques at high risk for standard revascularization; however, randomized controlled trials are needed to confirm its role in clinical practice.
17 Apr 2026
Read appraisal →Neurology
Outcomes After Minor Ischemic Stroke in Older Patients Treated With IV Thrombolysis vs Standard of Care in the TEMPO-2 Trial
BACKGROUND AND OBJECTIVES: There are few high-quality data on thrombolysis outcomes in the oldest patients, especially for minor stroke. We examined safety and efficacy outcomes of thrombolysis in patients older than 80 years, compared with those ≤80 years, in the Tenecteplase Versus Standard of care for Minor Ischaemic Stroke With Proven Occlusion (TEMPO-2) trial. METHODS: In this post hoc analysis of the TEMPO-2 randomized controlled trial, we compared outcomes and adverse events in patients with minor stroke and symptomatic intracranial occlusion or focal perfusion lesion within 12 hours of symptom onset, assigned to tenecteplase vs nonthrombolytic standard of care, in those >80 years and ≤80 years. The primary outcome was responder analysis of the 90-day modified Rankin Scale (responder was mRS = 0-1 if premorbid mRS = 0-1, 0-2 if premorbid mRS = 2). Secondary outcomes included neurologic recovery according to the NIH Stroke Scale (NIHSS) at 5 days/discharge, vessel recanalization, Lawton Instrumental Activities of Daily Living Scale, EuroQol-5 Dimension (EQ-5D), and adverse events. We used mixed-effects Poisson, ordinal logistic, and quantile regression as appropriate, adjusted for sex, baseline NIHSS, and treatment assignment as fixed-effects and enrolling site as random effects. RESULTS: Among 884 patients in the intention-to-treat analysis (208 [23.5%] >80 years, 365 [41.6%] female). Significant interactions between age and treatment were observed for mRS responder, mRS 0-1, return to baseline function, EQ-5D index, and vessel recanalization. Patients >80 years generally fared worse with tenecteplase for mRS outcomes (mRS 0-1 in 49 [46.2%] vs 61 [59.8%] with control, adjusted risk ratio [aRR] 0.83, 95% CI 0.72-0.97), while among patients ≤80 years, there was no significant difference (249 [76.4%] vs 260 [74.7%], aRR 1.01, 95% CI 0.98-1.03). However, in both age groups, patients were more likely to achieve recanalization of visible occlusions (aRR ≤80 years 2.06, 95% CI 1.60-2.65, >80 years 2.77, 95% CI 2.21-3.47) and NIHSS = 0 at 5 days/discharge when assigned to tenecteplase (aRR ≤80 years 1.14, 95% CI 1.04-1.26, >80 years 1.21, 95% CI 1.10-1.33). Serious adverse events (SAEs) were more frequent with tenecteplase among patients >80 years (risk ratio 2.29, 95% CI 1.27-4.13), particularly hemorrhages and stroke progression/recurrence (any extra/intracranial hemorrhage in 5 [4.7%] vs 0 with standard of care, p = 0.026). DISCUSSION: Older patients (>80 years) with minor stroke and visible occlusion or perfusion lesion assigned to tenecteplase were more likely to achieve recanalization of occlusions and short-term neurologic recovery, as were younger patients, but they experienced worse 90-day outcomes with more frequent hemorrhagic and stroke progression/recurrence-related SAEs. Overall, these results, while post hoc, do not support thrombolysis for minor strokes in older patients. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT02398656. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients >80 years with minor stroke and visible occlusion or perfusion lesion, IV thrombolysis with tenecteplase is associated with worse functional outcomes at 90 days compared with nonthrombolytic standard of care therapies.
15 Apr 2026
Read appraisal →JAMA
Tenecteplase for Acute Non-Large Vessel Occlusion 4.5 to 24 Hours After Ischemic Stroke: The OPTION Randomized Clinical Trial
IMPORTANCE: The efficacy and safety of intravenous tenecteplase in non-large vessel occlusion acute ischemic stroke beyond 4.5 hours after symptom onset remain uncertain. OBJECTIVE: To assess the efficacy and safety of intravenous tenecteplase administered 4.5 to 24 hours after stroke onset in patients with non-large vessel occlusion and salvageable brain tissue. DESIGN, SETTING, AND PARTICIPANTS: This randomized, open-label, blinded end-point clinical trial was conducted at 48 centers in China. A total of 566 patients with non-large vessel occlusion stroke and evidence of potentially salvageable tissue determined on perfusion imaging presenting within 4.5 to 24 hours of the time last seen well were recruited between June 2, 2023, and August 4, 2025 (final follow-up, October 28, 2025). INTERVENTIONS: Patients were randomly assigned 1:1 using a minimization algorithm to receive intravenous tenecteplase (0.25 mg/kg; maximum dose, 25 mg; n = 282) or standard medical treatment (n = 284). MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin Scale at 90 days. Safety outcomes included symptomatic intracranial hemorrhage within 36 hours and mortality within 90 days. RESULTS: Among the 570 patients randomized, 566 were included in the primary analysis (median age, 68 [IQR, 59-75] years; 196 female [34.6%]). An excellent functional outcome was observed in 123 of 282 patients (43.6%) in the tenecteplase group and 97 of 284 (34.2%) in the control group (risk ratio, 1.28 [95% CI, 1.04-1.57]; P = .02). The incidence of symptomatic intracranial hemorrhage at 2.8% was higher with tenecteplase than with standard medical treatment at 0% (risk difference, 2.85% [95% CI, 1.16%-5.54%]; P = .004), and the mortality at 90 days was 5.0% and 3.2%, respectively (risk ratio, 1.57 [95% CI, 0.69-3.57]; P = .28). CONCLUSIONS AND RELEVANCE: Among patients with non-large vessel occlusion acute ischemic stroke and salvageable brain tissue, intravenous tenecteplase administered 4.5 to 24 hours after onset resulted in a greater likelihood of an excellent functional outcome at 90 days than standard care but had an increased risk of symptomatic intracranial hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05752916.
8 Apr 2026
Read appraisal →Journal of the American Heart Association
A Position Statement on Endovascular Models and Effectiveness Metrics for Mechanical Thrombectomy Navigation, on Behalf of the Stakeholder Taskforce for Artificial Intelligence-Assisted Robotic Thrombectomy (START)
Although we are making progress in overcoming infectious diseases and cancer, one of the major medical challenges of the mid-21st century will be the increasing prevalence of stroke. Occlusions in large vessels are especially debilitating, yet effective treatment-needed within hours to achieve best outcomes-remains limited because of geographic accessibility. One solution for improving timely access to mechanical thrombectomy in geographically diverse populations is the widespread deployment of robotic surgical systems. Artificial intelligence assistance may enable the safe and effective upskilling of operators in this emerging therapeutic delivery approach. Our aim was to establish consensus frameworks for developing and validating artificial intelligence-assisted robots for thrombectomy. Objectives included standardizing effectiveness metrics and defining reference testbeds across in silico, in vitro, ex vivo, and in vivo environments. To achieve this, we convened experts in neurointervention, robotics, data science, health economics, policy, statistics, and patient advocacy. Consensus was built through an incubator day, a Delphi process, and a final position statement. We identified that the 4 essential testbed environments each had distinct validation roles. Realism requirements vary: simpler testbeds should include realistic vessel anatomy compatible with guidewire and catheter use, whereas standard testbeds should incorporate deformable vessels. More advanced testbeds should include blood flow, pulsatility, and disease features, such as atheromatous plaques. There are 2 macroclasses of effectiveness metrics: one for in silico, in vitro, and ex vivo stages focusing on technical navigation (eg, path-following error), and another for in vivo stages, focused on clinical outcomes (eg, modified treatment in cerebral infarction scores). Patient safety is central, and not a barrier, to this technology's development. One requisite patient safety task needed now is to correlate in vitro measurements to in vivo complications.
8 Apr 2026
Read appraisal →AJNR. American journal of neuroradiology
Reliability of Pseudocontinuous Arterial Spin-Labeling in Ischemic Stroke and Comparison with Other Perfusion Techniques: Systematic Review and Meta-Analysis
BACKGROUND: Pseudocontinuous arterial spin-labeling (pCASL) is a noninvasive, gadolinium-free MRI technique for assessing brain perfusion. PURPOSE: The test-retest reliability of pCASL-derived CBF measurements in ischemic stroke (IS) were evaluated and pCASL metrics were compared with those from DSC, CTP, and PET. DATA SOURCES: Systematic searches were conducted in MEDLINE, EMBASE, and LILACS. Risk of bias and methodologic quality were evaluated using QUADAS-2 and Quality Appraisal for Reliability Studies tools. STUDY SELECTION: Eleven studies, encompassing 383 participants with IS were included. DATA ANALYSIS: Random-effects meta-analysis with inverse variance method and heterogeneity assessed using I 2 statistics were used. DATA SYNTHESIS: No PET studies were identified. Only 1 low-quality, high-risk-of-bias study assessed test-retest reliability, finding no significant differences in repeated absolute CBF measurements over time and excellent reliability across regions. Most studies comparing pCASL with DSC, and all comparing pCASL with CTP, had a low risk of bias. In the hyperacute phase of IS, pCASL and DSC showed no significant differences in infarct core relative CBF (95% CI, -0.11 to 0.13; I 2 = 0%) or hypoperfusion volumes (95% CI, -0.28 to 0.68; I 2 = 69%). Evidence on the comparability of pCASL with other DSC or CTP metrics was limited. LIMITATIONS: The small number of included studies prevented a meta-analysis for the primary outcome and limited conclusions for secondary outcomes. CONCLUSIONS: Robust conclusions about the test-retest reliability of pCASL or the comparability of metrics obtained with this technique and DSC, CTP, or PET in different phases after IS could not be drawn.
5 Apr 2026
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