Meeting NewsPerspective

Alteplase effective up to 9 hours after ischemic stroke

Bruce C.V. Campbell
Bruce C.V. Campbell

In a meta-analysis presented at the European Stroke Organization Conference, alteplase was more effective than placebo for treatment of acute ischemic stroke between 4.5 and 9 hours after onset.

Guidelines recommend the use of a tissue plasminogen activator such as alteplase within 4.5 hours of acute ischemic stroke onset, but the researchers analyzed whether perfusion imaging could identify whether patients could benefit from alteplase after 4.5 hours or upon waking up with stroke symptoms.

Bruce C.V. Campbell, PhD, professor of medicine at Melbourne Brain Centre and Royal Melbourne Hospital, University of Melbourne, Australia, and colleagues conducted a systematic review and meta-analysis of 414 patients from three trials who were assigned alteplase (mean age, 73 years; 56% men) or placebo (mean age, 72 years; 58% men) after waking up with acute ischemic stroke symptoms or presenting with them between 4.5 and 9 hours after onset and were imaged with CT perfusion or perfusion-diffusion MRI. The results were simultaneously published in The Lancet.

The primary outcome was excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0 or 1, at 3 months.

The primary outcome was achieved in 36% of patients in the alteplase group and 29% of the placebo group (adjusted OR = 1.86; 95% CI, 1.15-2.99), according to the researchers.

Symptomatic intracranial hemorrhage occurred in 5% of the alteplase group vs. less than 1% of the placebo group (aOR = 9.7; 95% CI, 1.23-76.55).

“However, this did not negate the benefit of alteplase in ordinal analysis of the mRS, which accounts for transitions across the disability spectrum,” Campbell and colleagues wrote in The Lancet.

There was no significant difference between the groups in mortality (alteplase, 14%; placebo, 9%; aOR = 1.55; 95% CI, 0.81-2.96).

“This pooled analysis provides strong evidence in support of thrombolysis for patients with favorable perfusion imaging 4.5 to 9 hours after stroke, including patients with wake-up stroke,” Campbell and colleagues wrote.

In a related editorial in The Lancet, Shelagh B. Coutts, MD, MSc, and Bijoy K. Menon, MBBS, MD, MSc, both associate professors of medicine at the University of Calgary, wrote, “These findings should not prevent referral of a patient for endovascular clot retrieval, but might allow the use of thrombolysis as a bridge therapy during transport or a stand-alone treatment in settings where endovascular clot retrieval is not available.” – by Erik Swain

In a meta-analysis presented at the European Stroke Organization Conference, alteplase was more effective than placebo for treatment of acute ischemic stroke between 4.5 and 9 hours after onset.
Source: Adobe Stock

References:

Campbell BCV, et al. Official Welcome and Large Clinical Trials. Presented at: European Stroke Organization; May 22-24, 2019; Milan.

Campbell BCV, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)31053-0.

Coutts SB, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)31095-5.

Disclosures: Campbell reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Bruce C.V. Campbell
Bruce C.V. Campbell

In a meta-analysis presented at the European Stroke Organization Conference, alteplase was more effective than placebo for treatment of acute ischemic stroke between 4.5 and 9 hours after onset.

Guidelines recommend the use of a tissue plasminogen activator such as alteplase within 4.5 hours of acute ischemic stroke onset, but the researchers analyzed whether perfusion imaging could identify whether patients could benefit from alteplase after 4.5 hours or upon waking up with stroke symptoms.

Bruce C.V. Campbell, PhD, professor of medicine at Melbourne Brain Centre and Royal Melbourne Hospital, University of Melbourne, Australia, and colleagues conducted a systematic review and meta-analysis of 414 patients from three trials who were assigned alteplase (mean age, 73 years; 56% men) or placebo (mean age, 72 years; 58% men) after waking up with acute ischemic stroke symptoms or presenting with them between 4.5 and 9 hours after onset and were imaged with CT perfusion or perfusion-diffusion MRI. The results were simultaneously published in The Lancet.

The primary outcome was excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0 or 1, at 3 months.

The primary outcome was achieved in 36% of patients in the alteplase group and 29% of the placebo group (adjusted OR = 1.86; 95% CI, 1.15-2.99), according to the researchers.

Symptomatic intracranial hemorrhage occurred in 5% of the alteplase group vs. less than 1% of the placebo group (aOR = 9.7; 95% CI, 1.23-76.55).

“However, this did not negate the benefit of alteplase in ordinal analysis of the mRS, which accounts for transitions across the disability spectrum,” Campbell and colleagues wrote in The Lancet.

There was no significant difference between the groups in mortality (alteplase, 14%; placebo, 9%; aOR = 1.55; 95% CI, 0.81-2.96).

“This pooled analysis provides strong evidence in support of thrombolysis for patients with favorable perfusion imaging 4.5 to 9 hours after stroke, including patients with wake-up stroke,” Campbell and colleagues wrote.

In a related editorial in The Lancet, Shelagh B. Coutts, MD, MSc, and Bijoy K. Menon, MBBS, MD, MSc, both associate professors of medicine at the University of Calgary, wrote, “These findings should not prevent referral of a patient for endovascular clot retrieval, but might allow the use of thrombolysis as a bridge therapy during transport or a stand-alone treatment in settings where endovascular clot retrieval is not available.” – by Erik Swain

In a meta-analysis presented at the European Stroke Organization Conference, alteplase was more effective than placebo for treatment of acute ischemic stroke between 4.5 and 9 hours after onset.
Source: Adobe Stock

References:

Campbell BCV, et al. Official Welcome and Large Clinical Trials. Presented at: European Stroke Organization; May 22-24, 2019; Milan.

Campbell BCV, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)31053-0.

Coutts SB, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)31095-5.

Disclosures: Campbell reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Larry B. Goldstein

    Larry B. Goldstein

    Alteplase is FDA-approved in the U.S. for treatment within 3 hours of symptom onset. National guidelines endorse the use of IV tPA in selected patients up to 4.5 hours, but this represents off-label use. I am not aware of data reflecting the use of IV tPA in the U.S. after 4.5 hours. The 2018 American Heart Association Acute Stroke Guidelines do not address the use of alteplase beyond 4.5 hours of symptom onset. If there is a change in national guideline recommendations, practice would change accordingly. This is a systematic review and meta-analysis and as such, does not provide any new data.

    The benefits of alternative thrombolytics or combination with neuroprotective drugs could provide evidence further supporting longer delays between symptom onset and treatment.

    • Larry B. Goldstein, MD, FAAN, FANA, FAHA
    • Cardiology Today Editorial Board Member
      University of Kentucky

    Disclosures: Goldstein reports no relevant financial disclosures.