A machine learning study of the effect of thrombolysis on outcome at discharge in the UK stroke registry: how does benefit compare with clinical trials?

INTRODUCTION: Thrombolysis has been shown to reduce disability after acute ischaemic stroke in randomised trials. Our study sought to compare the benefit from thrombolysis observed in a comprehensive national stroke registry with that expected from the clinical trials. PATIENTS AND METHODS: Data from a total of 168,347 ischaemic stroke patients who attended one of 118 emergency stroke hospitals in England and Wales from 2016 to 2021 were extracted from the Sentinel Stroke National Audit Programme. We constructed a machine learning model, designed to isolate the effect of thrombolysis, using explainable machine learning (XGBoost with SHapley Additive exPlanations [SHAP]). RESULTS: Thrombolysis was found to be associated with a statistically significant improvement in the odds of achieving a better outcome (modified Rankin scale [mRS] threshold). Regression analysis predicted a maximum 2.5-fold improvement in odds of achieving mRS 0-1, with a decline to no treatment effect at 5 h 28 min post-onset. DISCUSSION: Our results confirm a beneficial effect of thrombolysis in a large prospective national stroke registry, and align closely with meta-analyses of clinical trials of thrombolysis both in terms of magnitude of effect and decline over time. This work also demonstrates the potential to apply explainable machine learning to observational data to assist in understanding how clinical trials are implemented in real-world settings. CONCLUSIONS: Thrombolysis, in practice, has the same observed benefit as in the clinical trials.