Safety of Early Rehabilitation Dose After Stroke on Composite Outcomes: Analysis of Nationwide Japanese Medical Claims Data

INTRODUCTION: Early rehabilitation guidelines lack a consensus on the optimal early rehabilitation regimen; hence, the impact of rehabilitation timing and dose on stroke recovery outcomes remains unclear. Using Japanese medical claims data within a target trial emulation framework, this study evaluated the safety of early in-hospital rehabilitation after stroke. PATIENTS AND METHODS: This study analyzed patients aged ≥ 18 years who were admitted to an acute hospital for acute stroke and received in-hospital rehabilitation within 2 days after admission, using the Japan Diagnosis Procedure Combination database (2018-2022). Rehabilitation exposures were defined as 6 predefined regimens (20-60 min/day initiated on days 1 or 2) and continued up to day 14. The outcome was the cumulative incidence of composite adverse events within 15 days after admission. A sequential, doubly robust estimator with a longitudinal modified treatment policy was applied, accounting for time-varying exposures and reducing potential time-related biases. RESULTS: Using a target trial emulation framework with doubly robust estimation, the incidence under the reference regimen was 11.2% (95% CI: 9.75%-12.60%). The highest incidence was 26.20% (95% CI: 24.30%-28.20%), corresponding to a risk ratio (RR) of 2.35 (95% CI: 2.03-2.72) compared with the reference. In contrast, several higher-intensity regimens were associated with lower incidences, with the lowest incidence of .49% (95% CI: .28%-.71%), yielding an RR of .04 (95% CI: .03-.07) versus the reference. However, intermediate-dose regimens showed variable associations across scenarios. DISCUSSION AND CONCLUSION: In this emulated trial, higher early rehabilitation doses were generally associated with a lower incidence of in-hospital adverse events. Regimens involving 60 min/day, particularly when initiated on day 1, showed the lowest estimated risk. However, the associations were not strictly linear, as intermediate-dose regimens demonstrated variable results across analyses. These findings suggest a potential benefit of adequately dosed early rehabilitation when clinically appropriate, while highlighting the importance of careful patient selection and monitoring.