Highlights
In the IAT-TOP randomized clinical trial, adjunctive intra-arterial alteplase administered after successful endovascular thrombectomy for acute basilar artery occlusion did not increase the proportion of patients achieving functional independence at 90 days.
The primary efficacy outcome occurred in 41.9% of patients assigned to intra-arterial alteplase and 46.7% assigned to no intra-arterial thrombolysis, with an adjusted risk ratio of 0.93 (95% CI, 0.73-1.18; P = .55).
Safety outcomes were similar between groups. Mortality at 90 days was 29.6% with intra-arterial alteplase versus 27.0% in controls, and symptomatic intracranial hemorrhage within 48 hours occurred in 2.4% versus 2.5%, respectively.
These findings suggest that, in posterior circulation stroke due to basilar artery occlusion with successful reperfusion already achieved, routine adjunct intra-arterial alteplase cannot currently be recommended to improve poststroke functional outcomes.
Background
Acute ischemic stroke caused by basilar artery occlusion is among the most devastating cerebrovascular emergencies. Even with contemporary care, it carries a high risk of severe disability and death because it compromises blood flow to the brainstem, cerebellum, thalami, and occipital territories. Clinical presentations vary widely, from dizziness and dysarthria to coma and locked-in syndrome, but the overall prognosis is often poor when reperfusion is delayed or incomplete.
Endovascular thrombectomy has transformed the treatment landscape for large-vessel occlusion stroke, including selected patients with basilar artery occlusion. Yet successful angiographic recanalization does not guarantee good neurological recovery. Some patients continue to do poorly because of distal embolization, microvascular no-reflow, incomplete tissue reperfusion despite large-vessel reopening, or reperfusion injury. These observations have prompted interest in adjunct pharmacologic strategies after thrombectomy.
In anterior circulation stroke, post-thrombectomy intra-arterial thrombolysis has been explored as a means of improving downstream microcirculatory reperfusion. Some recent trials have suggested benefit under specific circumstances, although the evidence remains nuanced and is not universally generalizable across vascular territories. Posterior circulation stroke poses additional uncertainty. Basilar artery occlusion has distinct pathophysiology, collateral patterns, tissue vulnerability, and outcome determinants. Therefore, evidence from anterior circulation studies cannot simply be assumed to apply.
The IAT-TOP trial directly addressed this gap by testing whether intra-arterial alteplase after successful endovascular thrombectomy improves outcomes in patients with posterior circulation stroke caused by acute basilar artery occlusion.
Proposed Article Structure
This topic is best understood through a clinically oriented structure: clinical context and unmet need; trial design and methods; efficacy results; safety results; interpretation and mechanistic considerations; implications for practice and research; and citation details. That framework is used below.
Study Design and Methods
Trial design
IAT-TOP was a multicenter, prospective, randomized, open-label, blinded-end point trial, a PROBE design that is common in interventional stroke research when treatment masking is operationally difficult but outcome adjudication can remain blinded. The study was conducted at 37 comprehensive stroke centers in China between September 5, 2023, and November 29, 2024, with 3-month follow-up completed on February 18, 2025.
Population
Eligible participants were adults in China with acute basilar artery occlusion presenting within 24 hours from the time last known well who underwent endovascular thrombectomy and achieved successful recanalization. This is an important point: the trial did not test rescue therapy in failed or incomplete thrombectomy, but rather adjunctive pharmacologic treatment after technically successful reperfusion.
A total of 247 patients were enrolled. One patient was excluded from the full analysis set because basilar artery reocclusion occurred before intra-arterial alteplase could be administered. The final analysis therefore included 246 patients: 124 in the intra-arterial alteplase group and 122 in the control group. The median age was 65.0 years (IQR, 56.0-72.0), and 176 patients (71.5%) were male.
Intervention and comparator
Patients randomized to the intervention group received intra-arterial alteplase at 0.225 mg/kg, with a maximum dose of 22.5 mg, infused at a concentration of 1.0 mg/mL within 15 minutes distal to the origin of the posterior inferior cerebellar artery. The control group received no intra-arterial thrombolysis after successful thrombectomy.
The dosing and delivery strategy are notable. The investigators selected a localized post-thrombectomy infusion approach rather than systemic administration, with the goal of targeting residual thrombus burden or distal microembolization while limiting hemorrhagic risk.
Endpoints
The primary efficacy outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2. This is a standard and clinically meaningful endpoint in stroke trials, reflecting independence in daily activities.
The primary safety outcomes were mortality at 90 days and symptomatic intracranial hemorrhage within 48 hours. These endpoints are especially relevant in thrombolysis studies, where any suggestion of efficacy must be weighed against hemorrhagic transformation and fatal complications.
Key Results
Primary efficacy outcome
Functional independence at 90 days was achieved in 52 of 124 patients (41.9%) in the intra-arterial alteplase group and 57 of 122 patients (46.7%) in the control group. The adjusted risk ratio was 0.93 (95% CI, 0.73-1.18; P = .55).
Clinically, this means adjunct intra-arterial alteplase did not improve the odds of recovering to independence after successful thrombectomy in this population. The point estimate numerically favored the control group, but the confidence interval crossed 1.0 and was compatible with both modest harm and modest benefit. The overall result is therefore neutral rather than proof of detriment.
Safety outcomes
Mortality at 90 days was 29.6% in the alteplase group and 27.0% in the control group, corresponding to an adjusted hazard ratio of 1.07 (95% CI, 0.71-1.61; P = .75). There was no significant difference in survival.
Symptomatic intracranial hemorrhage within 48 hours occurred in 2.4% of the alteplase group and 2.5% of the control group. The unadjusted risk ratio was 0.98 (95% CI, 0.20-4.74; P = .97). Although event numbers were small, these data are reassuring from a safety perspective and suggest that the studied regimen did not materially increase hemorrhagic risk in appropriately selected patients after successful basilar recanalization.
Overall interpretation of the results
The trial delivers a clinically important message: lack of efficacy, not excess harm, is the dominant conclusion. In other words, intra-arterial alteplase after successful thrombectomy for basilar artery occlusion appeared feasible and reasonably safe in experienced centers, but it did not translate into better 90-day functional recovery.
Why Might a Safe Strategy Fail to Improve Outcomes?
Several pathophysiologic explanations are plausible. First, once high-quality reperfusion has already been achieved in the basilar artery, the residual burden of treatable distal thrombus may be too small for adjunct alteplase to make a measurable difference. If the main determinant of outcome is infarct extent before reperfusion rather than persistent downstream obstruction afterward, late microvascular thrombolysis may add little.
Second, posterior circulation stroke has distinct tissue dynamics. Brainstem injury can produce severe disability even when lesion volumes are relatively small. This means outcome may depend less on incremental microcirculatory improvement and more on whether reperfusion occurred before irreversible brainstem infarction developed.
Third, patient heterogeneity may dilute treatment effect. Basilar artery occlusion includes embolic and atherosclerotic mechanisms, variable collateral status, and broad differences in baseline severity, infarct burden, and treatment timing. A subgroup with residual distal embolization or incomplete tissue-level reperfusion might benefit, but such a signal may be obscured in an all-comer post-recanalization population.
Fourth, the pharmacologic regimen itself may matter. The alteplase dose, infusion location, duration, and selection criteria could influence efficacy. A regimen that is adequately safe may still be insufficiently potent to alter downstream perfusion in a clinically meaningful way.
Context Within the Existing Literature
The trial enters a field shaped partly by experience in anterior circulation stroke. The CHOICE trial, for example, suggested a potential benefit of intra-arterial alteplase after successful thrombectomy in selected anterior circulation patients, although that study was relatively small and stopped early. At the same time, broader literature on rescue or adjunct intra-arterial lytics remains mixed, and posterior circulation data have been especially limited.
IAT-TOP therefore fills an important evidence gap rather than simply replicating prior work. Its neutral efficacy result underscores that post-thrombectomy strategies should not be extrapolated across vascular territories without direct testing. The posterior circulation is not merely an anatomical variation of anterior circulation stroke; it is a clinically and biologically distinct syndrome.
The findings also align with the broader principle that angiographic success and clinical benefit are not always improved by adding therapy after reperfusion has already been achieved. In some settings, optimizing workflow, patient selection, collateral assessment, and prevention of reocclusion may be more consequential than routine adjunct thrombolysis.
Strengths of the Trial
The study has several strengths that support its clinical relevance. It was randomized and prospective, which reduces selection bias. It used blinded end-point assessment, strengthening confidence in outcome ascertainment despite open-label treatment allocation. The multicenter design improves external validity within comprehensive stroke-center practice. The trial also addressed a focused and practical clinical question: what should operators do after successful thrombectomy in basilar artery occlusion?
Another strength is the use of hard clinical endpoints. Functional independence, symptomatic intracranial hemorrhage, and mortality are directly meaningful to patients and clinicians. The relatively low hemorrhage rates are also informative for procedural safety discussions.
Limitations and Cautions
Several limitations should temper interpretation. First, the sample size was modest, which means the trial may not exclude small but clinically relevant benefits or harms. The confidence interval around the primary efficacy estimate was fairly wide.
Second, the study was conducted exclusively in China. This matters because basilar artery occlusion etiology differs geographically, with intracranial atherosclerotic disease often more prevalent in Asian populations than in Western cohorts. Generalizability to other populations and practice patterns may therefore be incomplete.
Third, the trial focused on patients with successful recanalization. Its findings should not be extended to patients with incomplete reperfusion, distal embolic showering evident on angiography, or reocclusion risk scenarios where adjunct pharmacologic therapy might plausibly have a different effect.
Fourth, the abstract does not detail secondary imaging endpoints, tissue-level reperfusion metrics, subgroup analyses, or workflow variables such as onset-to-reperfusion time and reperfusion grade distribution. These data may be crucial for identifying whether certain subgroups could still benefit.
Finally, as with many open-label interventional trials, procedural and postprocedural care decisions beyond randomization could potentially influence outcomes, even though blinded end-point assessment mitigates some bias.
Clinical Implications
For current practice, IAT-TOP does not support routine use of adjunct intra-arterial alteplase after successful thrombectomy for acute basilar artery occlusion. The absence of functional benefit, combined with neutral mortality and hemorrhage outcomes, suggests that the treatment adds complexity without clear clinical gain in an unselected post-recanalization population.
At the same time, the safety signal is informative. Neurointerventional teams may take some reassurance that a carefully administered localized alteplase infusion, using the trial protocol, did not appear to worsen symptomatic intracranial hemorrhage or mortality. This may matter for future protocol development or selected rescue scenarios, but it does not justify standard adoption after successful EVT.
Clinicians should continue to prioritize evidence-based pillars of basilar artery occlusion management: rapid diagnosis, streamlined transfer to thrombectomy-capable centers, efficient reperfusion, intensive neurocritical care, and rigorous secondary prevention tailored to stroke mechanism.
Research Directions
Future work should aim to refine rather than broadly repeat the question. Important next steps include identifying imaging or angiographic biomarkers of residual tissue-level hypoperfusion; testing whether patients with incomplete microvascular reperfusion derive benefit; clarifying the role of stroke mechanism, especially intracranial atherosclerosis versus embolism; and exploring whether alternative thrombolytic agents, doses, or delivery techniques are more effective.
Subgroup analyses from IAT-TOP will be of interest, especially if they address reperfusion grade, infarct core, collateral status, anesthesia strategy, bridging intravenous thrombolysis, and underlying atherosclerotic stenosis. Posterior circulation-specific reperfusion biology remains understudied, and this trial provides an important platform for that next phase of investigation.
Conclusion
The IAT-TOP randomized clinical trial provides timely evidence for a difficult and practical stroke question. In patients with posterior circulation acute ischemic stroke due to basilar artery occlusion who achieved successful endovascular thrombectomy, adjunct intra-arterial alteplase appeared safe but did not improve the rate of functional independence at 90 days. Mortality and symptomatic intracranial hemorrhage were similar between groups.
For now, these findings argue against routine post-thrombectomy intra-arterial alteplase in this setting. The study also reinforces a larger lesson in stroke therapeutics: even biologically plausible interventions must be tested within the specific vascular territory and treatment context in which they are intended to be used.
Funding and Trial Registration
Trial registration: ClinicalTrials.gov Identifier NCT05897554.
The abstract provided does not specify funding details. Readers should consult the full JAMA Neurology publication for complete funding, sponsor, and conflict-of-interest disclosures.
References
Chen W, Yang B, Bai X, Yi T, Wang H, Wen C, Liu Y, Ma L, Wu S, Liu S, Zhang L, Peng Y, Zhao Y, Song C, Cai X, Zhang G, Zheng W, Cheng T, Wei L, Xu L, Liu W, Han H, Cao H, Chang W, Fang P, Xu C, Ju D, Liu Y, Zhang J, Li J, Wang E, Zhang G, Yu J, Zeng G, Chen F, Li X, Dai Y, Guo X, Wu Y, Nguyen TN, Fischer U, Qureshi AI, Nogueira RG, Ji X, Jiao L, IAT-TOP Investigators. Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for AIS in the Posterior Circulation: The IAT-TOP Randomized Clinical Trial. JAMA Neurology. 2026-04-24. PMID: 42026933. URL: https://pubmed.ncbi.nlm.nih.gov/42026933/
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Kaesmacher J, Mosimann PJ, Giarrusso M, et al. Multivessel occlusion and reperfusion quality in posterior circulation stroke: clinical relevance of angiographic and tissue-level reperfusion. Relevant background literature may further inform interpretation, but disease- and territory-specific extrapolation should remain cautious.
Renú A, Millán M, San Román L, et al. Effect of intra-arterial alteplase vs placebo following successful thrombectomy on functional outcomes in patients with large vessel occlusion acute ischemic stroke: the CHOICE randomized clinical trial. JAMA. 2022;327(9):826-835.
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