ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Cerebrolysin, hemorrhagic transformation, and anticoagulation timing after reperfusion therapy in stroke: post hoc secondary analysis of the CEREHETIS trial
Provisionally accepted
- 1Interregional Clinical Diagnostic Center, Kazan, Russia
- 2Kazan State Medical University, Kazan, Russia
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Background: The optimal timing of anticoagulation resumption after acute ischemic stroke remains uncertain, particularly in patients at elevated risk of hemorrhagic transformation (HT). Although Cerebrolysin reduces HT incidence, its influence on dynamic HT risk and the safe anticoagulation window remains unclear. Methods: This post hoc secondary survival analysis of the CEREHETIS trial (ISRCTN87656744) included 238 patients with intravenous thrombolysis (IVT)–treated middle cerebral artery (MCA) infarction. Patients were categorized into low (HTI 0) and high (HTI 1–4) HT-risk groups. Fourteen-day HT hazard trajectories were modeled using the Gompertz distribution. Nonlinear hazard acceleration (NLHA) and the compounding effect—reflecting self-amplifying instantaneous risk—were used to identify the inception point at which hazard stabilization may permit anticoagulation. A conservative NLHA threshold (0.23–0.44%/day) defined this risk-equilibrium. Results: In high-risk patients, Cerebrolysin significantly reduced symptomatic HT (HR 0.245; 95% CI 0.072–0.837; p=0.020) and any HT (HR 0.543; 95% CI 0.297–0.991; p=0.032). In controls, the compounding effect peaked on day 1 and persisted into day 2, whereas Cerebrolysin attenuated this amplification and shortened the hazardous period. Inception points occurred on days 1–3 with Cerebrolysin vs. days 3–5 in controls. In low-risk patients, both groups reached stable hazard by day 2. Conclusion: In IVT-treated MCA stroke patients with HTI 0–4, Cerebrolysin may reduce HT hazard and advance the risk-equilibrium point by approximately 1–2 days. These findings are preliminary and hypothesis-generating, suggesting that Cerebrolysin may allow earlier—but individualized—anticoagulation resumption in selected high-risk patients, pending prospective validation.
Keywords: anticoagulation timing, Cerebrolysin, Hemorrhagic transformation, intravenous thrombolysis, Stroke, survival analaysis
Received: 14 Oct 2025; Accepted: 08 Dec 2025.
Copyright: © 2025 Kalinin and Khasanova. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mikhail N. Kalinin
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