Cerebrolysin, Hemorrhagic Transformation, and Anticoagulation Timing after Reperfusion Therapy in Stroke: Secondary Analysis of the CEREHETIS Trial

Background Evidence supports Cerebrolysin’s efficacy in reducing hemorrhagic transformation (HT), but its impact on the timing of resuming anticoagulation therapy in stroke patients remains unclear. Methods A post hoc survival analysis of the CEREHETIS trial (ISRCTN87656744) was conducted. Patients with middle cerebral artery infarction ( n  = 238) were categorized into low-risk (HTI = 0) and high-risk (HTI > 0) groups based on HTI scores. The 14-day follow-up included any HT and symptomatic HT as failure events. Hazard deceleration (HD) curves were generated using the Gompertz model to estimate changes in the hazard function over time. The inception point, defined as when the HD curve dropped below the 5% threshold, indicated a constant hazard function. Timing of restarting anticoagulation therapy was inferred from the inception points using the HD curves and the lower limit of their 95% confidence intervals (CI). Results In the HTI > 0 cohort, Cerebrolysin reduced the risk of symptomatic HT and any HT, with hazard ratios of 0.245 (95% CI 0.072–0.837; p  = 0.020) and 0.543 (95% CI 0.297–0.991; p  = 0.032), respectively. Inception points for resuming anticoagulation therapy occurred on days 2–3 for the Cerebrolysin group and days 4–5 for the control group. In the HTI = 0 cohort, Cerebrolysin was ineffective, with inception points for both groups at the two-day mark. Conclusion Cerebrolysin may reduce the risk of HT and allow for a 1-2-day earlier resumption of anticoagulation therapy in patients at high risk of HT. However, its benefit is limited in those with initially low HT risk.