The clinical scenario at the heart of the research is known as drip-and-ship. Most people who experience a large-vessel occlusion stroke, in which a major artery feeding the brain is blocked, arrive first at a primary stroke center, a community hospital equipped to diagnose stroke and administer thrombolytic drugs but not to perform endovascular thrombectomy, the catheter-based procedure that physically extracts the clot. Those patients must then be transferred to a comprehensive stroke center. During the transfer interval, which can span one to several hours, the blocked artery starves an ever-growing territory of brain tissue, and every minute of untreated ischemia destroys millions of neurons.

Whether to give thrombolysis before that transfer has been one of the most contested questions in stroke medicine. Intravenous thrombolysis uses drugs such as alteplase or tenecteplase to activate plasminogen and dissolve fibrin-rich clots, and it has long been standard care for eligible patients within four and a half hours of symptom onset. But after randomized trials such as DEVT, SKIP, DIRECT-SAFE, and MR CLEAN-NO IV suggested that thrombectomy alone might be sufficient for large-vessel occlusions, some physicians began questioning whether the added drug was worth the time, cost, and theoretical bleeding risk. Complicating matters, those trials mostly enrolled patients who were already at thrombectomy-capable centers, leaving the transfer population understudied.

Wang and colleagues set out to close that evidence gap. Following PRISMA 2020 reporting guidelines, they systematically searched PubMed, Embase, and ClinicalTrials.gov from database inception through July 2, 2026, identifying sixteen observational studies that compared intravenous thrombolysis with no thrombolysis before interhospital transfer in patients with large-vessel occlusion acute ischemic stroke. The primary efficacy outcome was excellent functional outcome, defined as a score of 0 to 1 on the modified Rankin Scale, a standard disability measure, at ninety days. Secondary outcomes included good functional outcome (modified Rankin Scale 0 to 2), arterial recanalization occurring during the interhospital interval, and poor outcome (scale scores of 5 to 6). Safety outcomes covered ninety-day mortality, symptomatic intracranial hemorrhage, hemorrhage of any kind, and parenchymal hematoma, a particularly damaging form of bleeding into the infarcted brain.

The results were striking. Pre-transfer thrombolysis was associated with a 72 percent higher odds of excellent functional outcome, with a pooled odds ratio of 1.72 and a 95 percent confidence interval of 1.47 to 2.01, a finding that reached the stringent threshold of p less than 0.00001. Good functional outcome showed a similar pattern, with an odds ratio of 1.64. Perhaps most remarkable was the effect on interhospital recanalization: patients who received the clot-dissolving drug before transfer were more than seven times as likely to have their blocked artery reopen before ever reaching the thrombectomy suite, with an odds ratio of 7.71. Spontaneous or drug-assisted reopening of the vessel during transport means that some patients arrive at the comprehensive center with blood flow already restored, potentially salvaging brain tissue that would otherwise have been lost.

The benefits extended to the worst outcomes as well. Patients treated with thrombolysis before transfer had 35 percent lower odds of ending up dead or fully dependent at ninety days, with an odds ratio of 0.65 for the composite poor outcome of modified Rankin Scale scores 5 to 6, and 31 percent lower odds of death, with an odds ratio of 0.69. Crucially, the safety signals showed no excess harm. The odds ratios for symptomatic intracranial hemorrhage (0.75), any intracranial hemorrhage (0.91), and parenchymal hematoma (1.43) all had confidence intervals crossing unity, indicating no statistically significant difference in bleeding risk between the treated and untreated groups.

Because observational studies are vulnerable to confounding, since sicker or atypical patients may be selected out of thrombolysis for legitimate clinical reasons, the researchers also performed adjusted analyses using the generic inverse variance method. These adjusted estimates confirmed the unadjusted picture. After accounting for measured differences between groups, pre-transfer thrombolysis remained significantly associated with excellent functional outcome (adjusted odds ratio 1.47), good functional outcome (adjusted odds ratio 1.61), interhospital recanalization (adjusted odds ratio 8.06), and reduced ninety-day mortality (adjusted odds ratio 0.64). The consistency of magnitude and direction across unadjusted and adjusted models strengthens the causal plausibility of the association, although randomized confirmation in the transfer population remains the gold standard.

The findings fit a coherent biological narrative that has emerged from earlier work. Studies of infarct core growth during transfer have shown that brain tissue continues to die during the interhospital interval, and that early recanalization dramatically slows this progression. Clinical prediction research on post-thrombolysis recanalization has demonstrated that a meaningful fraction of large-vessel occlusions reopen after thrombolytic administration, particularly in the hours following injection. A large individual participant data meta-analysis of six randomized trials published in the Lancet in 2023 similarly found that intravenous thrombolysis added value even when thrombectomy was performed. In the transfer setting specifically, recent work in Annals of Neurology and JAMA Neurology by Seners and colleagues has framed the interhospital interval as a promising therapeutic window in which thrombolysis can act while the clot remains otherwise untreated.

The practical implications are considerable for the geography of stroke care. Thrombectomy is a resource-intensive procedure requiring a neurointerventionalist, a biplane angiography suite, and round-the-clock anesthesia and neurocritical care support, and global access studies have shown that most of the world’s population lives far from a center capable of performing it. In hub-and-spoke telestroke networks, drip-and-ship remains the dominant model for reaching these patients. The new analysis suggests that in resource-limited settings where timely thrombectomy is simply not immediately accessible, administering thrombolysis at the primary stroke center before dispatching the ambulance is an effective reperfusion strategy that buys real, measurable benefit during transport. Some single-center studies have even suggested that spoke-administered thrombolysis shortens subsequent procedure time and reduces the number of device passes needed, likely because partially dissolved clots are easier to extract.

Several caveats temper the conclusions. All sixteen included studies were observational, so residual confounding by indication cannot be excluded, and the ongoing debate over thrombectomy with or without intravenous thrombolysis, including the recent tenecteplase-before-thrombectomy trial published in the New England Journal of Medicine, shows that the field is still actively evolving. Heterogeneity across studies in drug choice, timing, imaging selection, and transfer distance may also influence the pooled estimates. Nonetheless, by synthesizing the full evidence base specific to the transfer population, the meta-analysis provides the most precise answer to date. For the physicians deciding whether to start the infusion at a community hospital at two in the morning before loading a stroke patient into an ambulance, the message is now substantially clearer: the drug given before the wheels start turning appears to reopen vessels, save brain, and save lives, and it does so without adding hemorrhagic danger.

Subject of Research: Intravenous thrombolysis before interhospital transfer for endovascular thrombectomy in large-vessel occlusion stroke

Article Title: Intravenous thrombolysis use before interhospital transfer for thrombectomy: a systematic review and meta-analysis

Article References: Wang, Z., Chen, Y., Li, J., Yuan, B., Wang, W., Li, J., & Ma, Q. (2026). Intravenous thrombolysis use before interhospital transfer for thrombectomy: a systematic review and meta-analysis. Journal of Neurology, 273(10), Article 630. https://doi.org/10.1007/s00415-026-14173-6

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14173-6

Keywords: ischemic stroke, thrombolysis, thrombectomy, interhospital transfer, large-vessel occlusion, drip-and-ship, meta-analysis, recanalization, intracranial hemorrhage, stroke outcomes, tenecteplase, stroke centers