Renal dysfunction and outcomes for thrombolysis-treated stroke beyond 4.5 hours: Trace-Ⅲ post hoc analysis

Objective

Concerns regarding bleeding risks have limited the use of intravenous thrombolysis in acute ischemic stroke (AIS) patients with renal dysfunction (RD). This study investigated the impact of RD on the efficacy and safety of Tenecteplase (TNK) thrombolysis in AIS patients with large vessel occlusions (LVO) beyond the 4.5 h window.

Methods

This post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events–III (TRACE-III) Trial included 510 patients with LVO (4.5–24 h from onset) randomized to TNK (0.25 mg/kg) or standard medical treatment (SMT). Renal function was categorized as normal (eGFR ≥90 mL/min/1.73 m²), mild (eGFR 60–89), or moderate-to-severe RD (eGFR <60). Primary efficacy outcome was 90-day excellent functional outcome (modified Rankin Scale [mRS] 0-1). Safety outcomes included symptomatic intracerebral hemorrhage (sICH), mortality and moderate or severe bleeding within 90 days. Multivariable regression and linear models were used to assess treatment effects across eGFR strata.

Results

In normal renal function patients (n = 410), TNK showed numerically higher excellent outcomes (32.3 % vs. 24.2 %, RR=1.28, 95 % CI 0.94∼1.75) and improved secondary outcomes (neurological improvement, as defined by NIHSS score reduction at 24 h/72 h/7 d and reperfusion rates), albeit with increased sICH (3.2 % vs. 1.1 %, p = 0.05). For mild RD (n = 82), TNK demonstrated a non-significant trend toward better functional outcomes (40.6 % vs. 26.0 %, RR=1.52, 95 % CI 0.78∼2.96). In moderate-to-severe RD (n = 18), outcomes were inconclusive due to limited sample size.

Conclusion

TNK may benefit late-window LVO stroke patients with normal or mildly impaired renal function. The risk-benefit profile in moderate-to-severe RD remains uncertain, highlighting the need for larger prospective studies in this high-risk population.