Ischemic stroke - Emerging treatments

Alteplase for patients with unknown time of stroke onset, or between 4.5 and 9.0 hours after onset

In a patient with unknown time of stroke onset who is otherwise eligible for intravenous thrombolysis with alteplase, a finding of a diffusion-weighted imaging (DWI)-positive, fluid attenuation inversion recovery (FLAIR)-negative lesion on MRI, or a mismatch on CT perfusion showing the presence of penumbra, suggests the patient is likely to be within a time window for safe and effective thrombolysis.[238] There is emerging evidence that some patients who present to the emergency department between 4.5 and 9.0 hours after stroke onset may also benefit from alteplase guided by perfusion imaging.[122][123][157][239] There was a slight increase in the rate of symptomatic intracerebral hemorrhage in these trials. However, a subsequent meta-analysis did not identify increased risk in symptomatic hemorrhage.[123]

Low-dose alteplase

One systematic review concluded that low-dose alteplase is comparable to standard-dose alteplase in improving neurologic function and reducing mortality, and reduces the incidence of symptomatic intracranial hemorrhage compared with the standard dose, in patients with acute ischemic stroke.[240] One subsequent systematic review, which included a large randomized trial conducted mainly in Asia, reported that low-dose alteplase is not associated with lower risk of death or disability, death alone, or symptomatic intracranial hemorrhage.[241]

Edaravone

Edaravone is thought to act by scavenging free radicals. Intravenous administration of edaravone was associated with improved outcomes in stroke patients, and is recommended for treatment of acute ischemic stroke by Chinese and Japanese stroke care guidelines.[242][243] Edaravone is not approved for ischemic stroke in the US nor Europe.

Recombinant kallikrein-1 (KLK1)

A recombinant (synthetic) form of human tissue KLK1, a serine protease that plays an important role in the regulation of microcirculation, blood pressure, and blood flow, has received fast track designation from the Food and Drug Administration (FDA).[244] A randomized, double-blind, placebo-controlled trial is planned to assess efficacy and impact on stroke recurrence.

Novel rehabilitation techniques

A device that uses brain-computer interface control of a robotics-powered exoskeleton may help stroke survivors regain hand and arm function. The device is approved by the FDA for patients 18 years and older who are at least 6 months post-stroke to facilitate muscle re-education and for maintaining or increasing range of motion. An exoskeleton (robotic hand brace) opens and closes the affected hand using spectral power from electroencephalographic (EEG) signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb.[245]

Cilostazol

This is an emerging option in acute ischemic stroke that is comparable to aspirin in its efficacy and safety.[246][247] [ ] Long-term dual antiplatelet therapy with aspirin plus cilostazol was shown to be efficacious and safe for secondary prevention in patients with high-risk ischemic stroke in Japan.[248] In patients with stroke or transient ischemic attack attributable to 50% to 99% stenosis of a major intracranial artery, the addition of cilostazol to aspirin or clopidogrel might be considered to reduce recurrent stroke risk.[102]

Rivaroxaban plus aspirin

In one trial, low-dose rivaroxaban plus aspirin was associated with significant protection against future stroke compared with aspirin alone or rivaroxaban alone in people with a history of coronary artery disease or peripheral artery disease and previous stroke.[116]