Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. When someone has an acute ischemic stroke, urgent, effective, simple and reliable treatments will reduce their risks of disability or dying from their brain tissue damage. The treatments used vary around the world, and a drug called cerebrolysin and its analogues are widely used in post-Soviet countries, Eastern Europe, and Central and Southeast Asia. In October 2023, the latest update of the Cochrane review was published by researchers from Cochrane Russia based at the Russian Medical Academy of Continuing Professional Education and two of the authors, Dilyara Nurkhametova and Liliya Eugenevna Ziganshina, discuss it for this podcast.

Dilyara: Hello Liliya Eugenevna. Let's begin with a few words about the topic for the review.

Liliya Eugenevna: Hello, Dilyara. Briefly, the review is about a medicine called cerebrolysin and its Russian-made analogue – cortexin, which are used for people who've had an acute ischemic stroke. Cerebrolysin is believed to have neuroprotective and neurotropic properties and is widely used here in Russia, countries of the former Soviet Union, Eastern Europe, China and elsewhere in Asia, while Cortexin is particularly common in Russia and post-Soviet countries. We wanted to examine their potential benefits and any associated harms when used for people after an acute ischemic stroke.

Dilyara: So, was one of the main reasons for the review the fact that cerebrolysin-like agents are used so often for this type of stroke across Russia and Russian-speaking countries?

Liliya Eugenevna: That was one of the reasons but the main issue as we worked on the review was the drug's use as a potential neuroprotector. In ischemic stroke, the concept of “neuroprotection” includes the suppression of changes that lead to an influx of calcium ions, activation of the reactive oxygen species or free radicals, and cell necrosis. These ideas have stimulated the development of many potentially “neuroprotective” substances, some of which have been shown to be effective in animal studies. However, the evidence from clinical trials in patients continues to be problematic.

Dilyara: This seems to be an important question. Perhaps you could describe what we did to get an answer.

Liliya Eugenevna: We looked for studies in which patients who were receiving a standard treatment for acute ischemic stroke were randomized to receive either cerebrolysin or cortexin, or a placebo; and used these studies to investigate the effects on death and adverse events.

Dilyara: How much information was there?

Liliya Eugenevna: We found seven randomized trials with a total of nearly 1800 participants. These included a newly identified study for this update, which investigated the Russian-made cerebrolysin-like agent, Cortexin, which is actively marketed and promoted.

Dilyara: And what do the trials tell us about the effects of these drugs?

Liliya Eugenevna: When we combined the evidence, we found no benefit from cerebrolysin or cortexin. There was no obvious effect on deaths and the data from the four multicentre studies, which reported serious side effects, showed that cerebrolysin more than doubled the number of people with non-fatal serious adverse events.

Dilyara: That does not sound good for cerebrolysin, but would it still help to have a large clinical trial to resolve this issue once and for all?

Liliya Eugenevna: Although high-quality large-scale randomized trials are always necessary for getting reliable information about the potential value of drug treatments for acute ischemic stroke, our review has shown that the potential benefit of cerebrolysin and cortexin is not supported by reliable evidence and we would not recommend its routine use in acute ischemic stroke. We've also shown that the use of cerebrolysin and cerebrolysin-like agents is unsafe and, so, if it is going to be tested in future research, this needs to take the form of well-designed randomised trials and include assessments of the risks of serious adverse events.

Dilyara: So, to finish, what would be the advice for patients with acute ischemic stroke, their relatives, and doctors who treat and care for them; and how can listeners find the review?

Liliya Eugenevna: At its simplest, we'd say that cerebrolysin or cortexin are not the right choice for the treatment of acute ischemic stroke. And, to find the review, people should go online to Cochrane Library dot com and type "cerebrolysin and stroke" into the search box.

Dilyara: Thank you.