Cerebrolysin, hemorrhagic transformation, and anticoagulation timing after reperfusion therapy in stroke: post hoc secondary analysis of the CEREHETIS trial.

Kalinin MN, Khasanova DR

Frontiers in pharmacology7 Jan 2026

PMID41640685PMCIDPMC12865818DOI10.3389/fphar.2025.1725255PepBankPUB-41640685

Summary

BackgroundThe 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.MethodsThis 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.ResultsIn 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.ConclusionIn IVT-treated MCA stroke patients with HTI 1-4, 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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

01HumanOther designSafety outcome
In high-risk IVT-treated MCA infarction patients, Cerebrolysin reduced symptomatic hemorrhagic transformation versus controls.
In plain wordsIn high-risk stroke patients, Cerebrolysin reduced symptomatic hemorrhagic transformation compared with controls.
Peptide
Cerebrolysin
Outcome
DecreaseSymptomatic hemorrhagic transformation in high-risk patients
Study
n: not reported in source
Comparator
Controls
Analysis
Secondary
Outcome group
Adverse events · Nervous system and cognition
Studied dose
Dose not stated
Measurements
Hazard ratio
0.245
symptomatic HT
95% CI
0.072 to 0.837
symptomatic HT
P value
0.02
symptomatic HT
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc secondary survival analysis of the CEREHETIS trial (ISRCTN87656744) included 238 patients with intravenous thrombolysis (IVT)-treated middle cerebral artery (MCA) infarction.
Summary · context
Patients were categorized into low (HTI 0) and high (HTI 1-4) HT-risk groups.
Show in the study text Report a problemFND-4164068501
02HumanOther designSafety outcome
In high-risk IVT-treated MCA infarction patients, Cerebrolysin reduced any hemorrhagic transformation versus controls.
In plain wordsIn high-risk stroke patients, Cerebrolysin reduced any hemorrhagic transformation compared with controls.
Peptide
Cerebrolysin
Outcome
DecreaseAny hemorrhagic transformation in high-risk patients
Study
n: not reported in source
Comparator
Controls
Analysis
Secondary
Outcome group
Adverse events · Nervous system and cognition
Studied dose
Dose not stated
Measurements
Hazard ratio
0.543
any HT
95% CI
0.297 to 0.991
any HT
P value
0.032
any HT
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc secondary survival analysis of the CEREHETIS trial (ISRCTN87656744) included 238 patients with intravenous thrombolysis (IVT)-treated middle cerebral artery (MCA) infarction.
Summary · context
Patients were categorized into low (HTI 0) and high (HTI 1-4) HT-risk groups.
Show in the study text Report a problemFND-4164068502
03HumanOther designMechanism
In high-risk stroke patients, Cerebrolysin attenuated HT hazard amplification compared with controls.
In plain wordsIn high-risk stroke patients, Cerebrolysin reduced amplification of bleeding risk compared with controls.
Peptide
Cerebrolysin
Outcome
DecreaseHT hazard compounding effect
Study
n: not reported in source
Comparator
Controls
Analysis
Secondary
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Measurements
Time of compounding-effect peak
1 day
Controls, high HT-risk patients
Day into which compounding effect persisted
2 day
Controls, high HT-risk patients
Source sentences
Summary
In controls, the compounding effect peaked on day 1 and persisted into day 2, whereas Cerebrolysin attenuated this amplification and shortened the hazardous period.
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc secondary survival analysis of the CEREHETIS trial (ISRCTN87656744) included 238 patients with intravenous thrombolysis (IVT)-treated middle cerebral artery (MCA) infarction.
Summary · context
Patients were categorized into low (HTI 0) and high (HTI 1-4) HT-risk groups.
Show in the study text Report a problemFND-4164068503
04HumanOther designEfficacy outcome
In high-risk stroke patients, Cerebrolysin shortened the hazardous period compared with controls.
In plain wordsIn high-risk stroke patients, Cerebrolysin shortened the hazardous period compared with controls.
Peptide
Cerebrolysin
Outcome
DecreaseHazardous period
Study
n: not reported in source
Comparator
Controls
Analysis
Secondary
Outcome group
Adverse events · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
In controls, the compounding effect peaked on day 1 and persisted into day 2, whereas Cerebrolysin attenuated this amplification and shortened the hazardous period.
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc secondary survival analysis of the CEREHETIS trial (ISRCTN87656744) included 238 patients with intravenous thrombolysis (IVT)-treated middle cerebral artery (MCA) infarction.
Summary · context
Patients were categorized into low (HTI 0) and high (HTI 1-4) HT-risk groups.
Show in the study text Report a problemFND-4164068504
05HumanOther designEfficacy outcome
In high-risk stroke patients, inception points occurred on days 1-3 with Cerebrolysin versus days 3-5 in controls.
In plain wordsIn high-risk stroke patients, risk equilibrium occurred on days 1-3 with Cerebrolysin versus days 3-5 in controls.
Peptide
Cerebrolysin
Outcome
DecreaseRisk-equilibrium inception timing
Study
n: not reported in source
Comparator
Controls
Analysis
Secondary
Outcome group
Adverse events · Nervous system and cognition
Studied dose
Dose not stated
Measurements
Risk-equilibrium inception timing
1 to 3 days
Cerebrolysin, high HT-risk patients
Risk-equilibrium inception timing
3 to 5 days
Controls, high HT-risk patients
Approximate advancement of risk-equilibrium point
1 to 2 days
Cerebrolysin versus controls, IVT-treated MCA stroke patients with HTI 1-4; may advance
Source sentences
Summary
Inception points occurred on days 1-3 with Cerebrolysin vs. days 3-5 in controls.
Summary
In IVT-treated MCA stroke patients with HTI 1-4, Cerebrolysin may reduce HT hazard and advance the risk-equilibrium point by approximately 1-2 days.
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc secondary survival analysis of the CEREHETIS trial (ISRCTN87656744) included 238 patients with intravenous thrombolysis (IVT)-treated middle cerebral artery (MCA) infarction.
Summary · context
Patients were categorized into low (HTI 0) and high (HTI 1-4) HT-risk groups.
Show in the study text Report a problemFND-4164068505
06HumanOther designEfficacy outcome
In low-risk stroke patients, both Cerebrolysin and control groups reached stable hazard by day 2.
In plain wordsIn low-risk stroke patients, both Cerebrolysin and control groups reached stable hazard by day 2.
Peptide
Cerebrolysin
Outcome
Not applicableStable hazard in low-risk patients
Study
n: not reported in source
Comparator
Controls
Analysis
Secondary
Outcome group
Adverse events · Nervous system and cognition
Studied dose
Dose not stated
Measurements
Time to stable hazard
≤ 2 day
Low-risk patients, both Cerebrolysin and control groups; by day 2
Source sentences
Summary
In low-risk patients, both groups reached stable hazard by day 2.
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc secondary survival analysis of the CEREHETIS trial (ISRCTN87656744) included 238 patients with intravenous thrombolysis (IVT)-treated middle cerebral artery (MCA) infarction.
Summary · context
Patients were categorized into low (HTI 0) and high (HTI 1-4) HT-risk groups.
Show in the study text Report a problemFND-4164068506

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

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