Clot-busting meds may be effective up to 24 hours after initial stroke symptoms

These results give hope to stroke patients worldwide who may not be able to access clot-dissolving medications within the approved time window, which in China is within 4.5 hours, said the trial’s principal investigator Min Lou, M.D., Ph.D., a professor at the Second Affiliated Hospital of Zhejiang University’s School of Medicine in China.

In the U.S., alteplase is approved to treat stroke within three hours of symptom onset and is recommended for use up to 4.5 hours for select patients. Other research has indicated it may also work well in some patients 4.5 to 9 hours after stroke onset.

The American Heart Association/American Stroke Association 2019 Guidelines for the Early Management of Patients with Acute Ischemic Stroke note that IV alteplase within 4.5 hours of stroke onset is the standard of care for most ischemic stroke patients in the United States.

Researchers enrolled 372 stroke patients whose symptoms began 4.5 hours to 24 hours earlier. They used widely available CT perfusion imaging (advanced brain scanning) to confirm that these patients still had brain tissue that could recover with treatment. Participants were randomly split into two groups — one group received the clot-busting medication alteplase, while the other received standard stroke care of antiplatelet therapy at the discretion of the investigator, based on the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2018. Functional recovery was assessed at 90 days.

“We believe these findings mean more people may return to normal or near-normal lives after a stroke, even if they receive treatment later than originally thought beneficial,” Lou said. “This method of treatment could become the new standard, especially in hospitals that use CT perfusion imaging. This technology helps health care professionals see how blood flows in different parts of the brain after an ischemic stroke. This could extend treatment eligibility to millions more patients across the globe.”

The study found:

• 40% of participants treated with alteplase had little to no disability after 90 days, compared to 26% of those who received standard care — a 54% higher chance of functional recovery.
• Less than 3% of participants in either group received rescue mechanical clot removal as an additional treatment.
• Rates of death were the same (10.8%) for both groups.
• The risk of brain bleeding was higher among those who received alteplase than among participants who did not (3.8% vs. 0.5%), but researchers believe this is a manageable risk.

“We also need to look more closely at how safe and effective other clot-dissolving medications, like tenecteplase, are when given after a stroke, especially beyond the usual time frames. It’s also important to learn if our findings apply to other groups of people, especially in areas with different stroke risks and health care resources,” Lou explained.

Study limitations include the that both participants and researcher knew which treatment was being given, which could have introduced bias, and results may not be generalizable to patients outside of China.

Study design, background and details:

• The study enrolled 372 stroke patients in a multicenter, prospective, randomized trial at 26 stroke centers in China.
• The patient’s average age was 72 years, and 43% were women.
• The trial used widely available CT perfusion imaging software to gauge salvageable brain tissue, making the findings more applicable to real-world clinical settings.
• Enrolled patients were assigned to the alteplase group or a standard medical treatment group.
• The primary outcome was a score of 0 or 1 on the modified Rankin scale, which scores disability from 0 (no symptoms) to 6 (death) at 90 days.