Intra-arterial alteplase increases likelihood of excellent post-thrombectomy functional outcome

Intra-arterial alteplase (IAA) resulted in a higher likelihood of excellent functional outcome at 90 days among patients with acute, anterior-circulation, large-vessel occlusion (LVO) stroke who achieved successful endovascular reperfusion by mechanical thrombectomy, a study in China has found.

The prospective, open-label, PEARL clinical trial included 324 patients (median age, 68 years; female, 30.6 percent) from 28 hospitals in China who had anterior-circulation, LVO stroke within 24 hours of symptom onset and achieved successful reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] score of 2b50 to 3) after thrombectomy. They were randomized in a 1:1 ratio to receive 15-minute IAA infusion (0.225 mg/kg; maximum dose, 20 mg; n=164) or standard treatment (n=160). All participants, regardless of group assignment, received standard medical management that adhered to the latest clinical guidelines (which included intravenous [IV] thrombolytics received by 42.1 and 41.3 percent of patients in the IAA and standard treatment groups, respectively) and institutional practices. [JAMA 2025;doi:10.1001/jama.2025.16876]

IAA, compared with standard treatment, was associated with a significantly increased rate of achieving an excellent outcome (modified Rankin Scale [mRS] score of 0 or 1) at 90 days (44.8 vs 30.2 percent; adjusted risk ratio [aRR], 1.45; 95 percent confidence interval [CI], 1.08–1.96; p=0.01). However, the difference was not statistically significant for the overall degree of disability (ordinal mRS shift analysis). “This discrepancy may be partly attributed to an imbalance in mortality,” the authors postulated.

All-cause mortality within 90 days occurred in 17.1 percent of patients in the IAA group vs 11.3 percent of those in the standard treatment group (adjusted hazard ratio, 1.60; 95 percent CI, 0.88–2.89; p=0.12). “The increased procedural complexity associated with IAA administration may have contributed to higher mortality by prolonging procedure time and potentially compromising marginally perfused brain tissue, as reflected by a higher incidence of intracranial haemorrhage [ICH; proportion of patients with any ICH within 36 hours in the IAA vs standard treatment group was 32.9 vs 26.9 percent (aRR, 1.22; 95 percent CI, 0.92–1.63; p=0.17)],” explained the authors.

Subgroup analyses for the primary efficacy outcome on prespecified strata, such as IV thrombolysis and stroke severity before randomization, amongst others, showed no evidence of treatment effect modification, suggesting that the benefit of IAA was not modified by the degree of prior reperfusion.

Safety outcomes were comparable between the two groups. Symptomatic ICH occurred within 36 hours in 4.3 vs 5.0 percent of patients in the IAA vs standard treatment group (aRR, 0.85; 95 percent CI, 0.43-1.69; p=0.67).

“The findings from the current study align with those of the CHOICE and ANGEL-TNK trials,” noted the authors. “Compared with the neutral POST-TNK and POST-UK trials, which exclusively enrolled patients with eTICI scores of 2c and 3 and excluded those who received IV thrombolysis, both CHOICE and the current trial included patients with an eTICI score of 2b and those who had received IV thrombolysis.” [JAMA 2022;327:826-835; JAMA 2025;334:582-591; JAMA 2025;333:579-588; JAMA 2025;333:589-598]