Does the window for stroke treatment close after 4.5 hours? A new study changes the picture

When it comes to a stroke, time is critical: as the minutes pass, more brain tissue can be irreversibly damaged. For years, this principle was also translated into a clear treatment window of 4.5 hours for administering clot-dissolving drugs. However, a new broad study published in the medical journal JAMA Network Open indicates that for some patients, the clock does not tell the whole story. When brain imaging shows that there is tissue left that can be saved, treatment may be beneficial even hours later.

"A stroke is an acute manifestation of a disruption in the blood supply to a certain area of the brain, due to a blockage or narrowing of a blood vessel in the neck or inside the brain," explains Dr. Roni Eichel, Director of the Neurological Department and a stroke expert at the Shaare Zedek Medical Center. "Unfortunately, every year about 20,000 people in Israel suffer a stroke, and a significant portion of them remain with permanent disability as a result. In fact, a stroke is currently one of the leading causes of disability in the world." This disability can take various forms, depending on the area of the brain affected and the severity of the injury. It can manifest as significant weakness on one side of the body, in the arm and leg, in the loss of the ability to move or use the hand, and in cases where areas related to language are affected, also in difficulty speaking, communicating, or understanding the environment. "Ultimately, this can be a blow to a person's independence," he adds.

A large part of the risk factors for a stroke are also known from other vascular and heart diseases. Among the main ones, Dr. Eichel lists high blood pressure, diabetes, obesity, lack of physical activity, and smoking. Therefore, according to him, alongside the ability to treat a stroke after it has occurred, prevention is even more important: maintaining a healthy lifestyle and treating risk factors even before they lead to a stroke.

Time as a critical factor

Dr. Roni Eichel notes: "If the brain has already been extensively damaged, even a catheterization will not necessarily help. But if there is still brain tissue left that can be saved, it is possible in appropriate cases to intervene even up to 24 hours from the start of the stroke." But from the moment the stroke occurs, time becomes a critical factor. "The clock is ticking," emphasizes Dr. Eichel. "With every passing minute, about two million neurons in the brain die." This means that the time window in which one can intervene and try to save brain tissue is short, and any delay can affect the extent of the damage and the chances of recovery.

One of the main ways of treating an ischemic stroke is the intravenous infusion of a clot-dissolving drug, known as IV tPA. The goal of the treatment is to break down the clot that is blocking the artery and allow blood to flow again to the affected area of the brain. "This was the first treatment that actually helped change the fate of patients by opening the clots that block the arteries," says Dr. Eichel. "The treatment has existed in the world since 1995 and in Israel since 2002. Today, about 12% of patients who arrive with an ischemic stroke receive this treatment." Another option is brain catheterization, during which a catheter is used to reach the blocked blood vessel and remove the clot. However, not every patient is suitable for catheterization, as it depends on the location of the blockage and the size of the affected blood vessel.

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New study: expanding the boundaries

The researchers combined the results of 14 randomized clinical trials that included a total of 4,174 ischemic stroke patients. 2,102 of the patients received clot-dissolving treatment and 2,072 were in the control groups. In all the trials, the treatment was given 4.5 hours or more after the start of the stroke, or after the last time the patient was known to be without symptoms. In 11 out of 14 trials, advanced imaging was used, including CT and MRI, as part of patient selection.

The results showed an advantage for late treatment. Compared to the control groups, patients who received clot-dissolving treatment had a 22% higher relative chance of reaching an excellent functional result after 90 days, meaning to be without symptoms or without significant disability. Their relative chance of reaching a good functional result was 12% higher. The researchers also translated the data into practical meaning: for every 12 patients who receive the treatment, on average one additional patient is expected to reach an excellent functional result thanks to the treatment.

Risks and challenges

But expanding the time window also has a price. The meta-analysis found that the risk of symptomatic intracerebral hemorrhage was 2.44 times higher among patients who received a clot-dissolving drug. However, no significant difference was found in mortality after 90 days between the treatment group and the control group. According to the researchers' calculations, an additional event of symptomatic brain hemorrhage is expected to occur for approximately every 62 patients who receive the treatment.

"You need to choose patients very carefully, because this substance also has dangers," says Dr. Eichel. "One of the dangers is that opening the artery will lead to bleeding in the brain. There are very complex protocols for treating these patients over 4.5 hours. You need to know how to interpret the imaging, to understand the clinical context. This requires additional technological resources and manpower in hospitals, and the approach must be fast, because every minute counts." Dr. Eichel emphasizes that these data are especially significant in Israel, where accessibility to experts remains the biggest gap in increasing the number of patients receiving advanced treatments.