Early Thrombolysis Unlocks Maximum Benefit Prior to Thrombectomy in Acute Ischemic Stroke

In acute ischemic stroke driven by anterior-circulation large-vessel occlusion (LVO), the clinical debate surrounding whether to administer intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) vs. proceeding directly to EVT has centered on real-world effectiveness and time-sensitivity. A landmark multinational study utilizing data from the RES-Q (Registry of Stroke Care Quality) across 38 countries demonstrates that the additive benefit of IVT before EVT is strongly time-dependent. The study, led by first author Robert Mikulik, was co-authored by Geraldo Neto, a core researcher of the METRICS Research Consortium. The findings reveal that combined bridging therapy (IVT+EVT) significantly improves short-term functional independence and in-hospital survival—provided thrombolysis is delivered within early time windows post-symptom onset.

The Core Narrative (The Breakthrough)

While endovascular thrombectomy has established itself as the gold-standard treatment for large-vessel occlusion, real-world clinical practice often faces logistical delays in patient transfer, door-to-needle, and door-to-groin puncture times. To evaluate whether treatment timing modifies the clinical efficacy of bridging IVT before EVT compared to direct EVT alone, the research team analyzed a real-world cohort of 3,009 patients with anterior-circulation LVO across 38 countries enrolled in the RES-Q registry between 2022 and 2024.

To account for baseline clinical disparities and non-randomized treatment selection, the authors implemented stabilized inverse probability of treatment weighting (IPTW) incorporating vascular risk factors (hypertension, diabetes, atrial fibrillation, prior stroke), baseline NIHSS stroke severity scores, imaging modalities, and admission pathways. The analytic cohort was stratified into four precise onset-to-treatment time strata (≤100 minutes, >100–150 minutes, >150–255 minutes, and >255 minutes) to evaluate discharge functional outcomes via the modified Rankin Scale (mRS).

Key Findings & Clinical Interpretation

The analysis revealed a statistically significant treatment-by-time interaction for both ordinal shift in discharge mRS (P = 0.002) and favorable functional outcome (mRS; 0–2, P = 0.02). The additive clinical superiority of IVT prior to EVT was concentrated within the earliest therapeutic windows:

  • Ultra-Early Window (≤100 minutes): Patients receiving IVT+EVT demonstrated a nearly twofold increase in favorable discharge functional shift (adjusted Odds Ratio [aOR] 1.99; 95% CI, 1.49–2.63) and a 76% increase in functional independence (mRS ; 0–2: aOR 1.76; 95% CI, 1.24–2.51) compared to EVT alone. Crucially, early IVT+EVT was associated with an 81% increase in in-hospital survival (aOR 1.81; 95% CI, 1.13–2.92; 90.2% vs. 82.2%).
  • Early Window (>100–150 minutes): The clinical advantage remained robust, yielding higher odds of functional independence (mRS; 0–2: aOR 1.64; 95% CI, 1.16–2.31) and favorable ordinal shift (aOR 1.58; 95% CI, 1.21–2.06).
  • Attenuated Efficacy Beyond 150 Minutes: Beyond 150 minutes from onset to treatment, the additive benefit of pre-thrombectomy thrombolysis was markedly attenuated, showing no statistically significant superiority over direct EVT alone (>150–255 minutes mRS ordinal aOR 0.93; 95% CI, 0.71–1.48).

These real-world observational findings align closely with global trial meta-analyses, reinforcing the biological principle that early IVT promotes early recanalization or microvascular reperfusion before mechanical clot retrieval, but loses efficacy as clot burden becomes organized over time.

Clinical Implications & Future Directions

For stroke networks and health systems leadership, these findings provide crucial actionable evidence:

  1. System Speed is Paramount: The debate between direct EVT and bridging IVT should not be viewed as static. In centers where thrombolysis can be initiated rapidly (150 minutes), IVT should remain the frontline standard before EVT.
  2. Optimizing Drip-and-Ship Logistics: In primary stroke centers, initiating IVT immediately prior to inter-hospital transfer maximizes the window of early efficacy without delaying EVT dispatch.
  3. Refining Patient Selection: For delayed presentations (>150 minutes), direct EVT may be prioritized to minimize transfer delays or unnecessary medication costs, supporting personalized stroke care pathways.

Citation Block

Mikulik R, Neto G, Sedani R, Thalerová S, Bornstein NM, Gdovinová Z, Hill MD, Kobayashi A, Lavados PM, Martins S, Middleton S, Miglane E, Nguyen HT, Sohn SI, Suwanwela NC, Sylaja PN, Tsivgoulis G. Time-Dependent Efficacy of Thrombolysis Before Thrombectomy: RES-Q. Stroke. 2026;57(8):2315–2324. https://doi.org/10.1161/STROKEAHA.126.055656