In an adult with acute ischemic or hemorrhagic stroke who has received standard reperfusion and secondary‑prevention therapy, should Cerebrolysin be used as an adjunct, and what is the recommended dose and duration?

Cerebrolysin Should Not Be Used in Acute Stroke

Cerebrolysin cannot be recommended for routine use in adults with acute ischemic or hemorrhagic stroke, as current evidence shows no benefit on functional outcomes or mortality, with potential for increased non-fatal serious adverse events.

Evidence from Guidelines

The American Heart Association/American Stroke Association guidelines explicitly state that neuroprotective agents, including peptide-based therapies, cannot be recommended outside clinical trials 1. The guidelines note that while numerous neuroprotective interventions showed promise in experimental studies, most clinical trials have produced disappointing results, with some treated patients experiencing poorer outcomes than controls 1.

Combination therapies (including neuroprotective agents with reperfusion therapy) remain experimental and are not recommended for clinical practice 1. No data are available demonstrating the efficacy of neuroprotective interventions as complements to thrombolysis or other reperfusion therapies 1.

High-Quality Research Evidence

The Cochrane Systematic Review (2023)

The most recent and highest-quality evidence comes from a 2023 Cochrane systematic review analyzing 7 RCTs with 1,773 participants 2:

Primary Findings:

• All-cause death: Cerebrolysin probably results in little to no difference in mortality (RR 0.96,95% CI 0.65-1.41; moderate-certainty evidence) 2
• Serious adverse events: Cerebrolysin probably results in little to no difference in total SAEs, but shows an increase in non-fatal SAEs (RR 2.39,95% CI 1.10-5.23; moderate-certainty evidence) 2
• The increase in non-fatal SAEs was more prominent with the 30 mL for 10 days dosing schedule (RR 2.87,95% CI 1.24-6.69) 2

Meta-Analysis Findings (2017)

A comprehensive meta-analysis of 1,649 patients from 6 RCTs found 3:

• No significant effect on functional recovery at Day 90 by modified Rankin Scale (RR 1.33,95% CI 0.79-2.24, P=0.28) 3
• No benefit on NIHSS response (RR 1.03,95% CI 0.83-1.28, P=0.77) 3
• No benefit on Barthel Index (RR 0.95% CI 0.84-1.08, P=0.44) 3

Critical Limitations of Positive Studies

The CARS trials (2017) that showed some motor benefit had significant methodological concerns 4:

• These were industry-sponsored studies with pre-planned meta-analysis 4
• The benefit was primarily on surrogate motor outcomes, not on clinically meaningful functional independence 4
• The Cochrane review, which included broader outcomes and more recent data, contradicted these findings 2

Safety Concerns

Cerebrolysin carries a potential harm signal 2:

• Moderate-certainty evidence shows increased non-fatal serious adverse events 2
• The risk-benefit ratio does not favor its use given the lack of functional benefit 2
• One small trial showed potential cognitive benefit, but this was not replicated in larger, higher-quality studies 5

Clinical Bottom Line

Do not use Cerebrolysin in acute stroke management 1, 2. Focus instead on:

• Evidence-based reperfusion therapy (IV alteplase within 4.5 hours or mechanical thrombectomy for large vessel occlusion) 1
• Early aspirin (160-325 mg within 48 hours, but not within 24 hours of thrombolysis) 1, 6
• Standard secondary prevention measures 1

Common Pitfall: Clinicians in regions where Cerebrolysin is marketed may feel pressure to use it. However, the absence of benefit on patient-centered outcomes (death, disability, quality of life) combined with potential for harm makes its use unjustifiable in evidence-based practice 2, 3.