Ischemic stroke - Emerging treatments

Reteplase

Reteplase is another recombinant tissue plasminogen activator (r-tPA) currently approved in the US and Europe for acute myocardial infarction (MI). However, trials show promise in patients with ischemic stroke. One phase 2 open-label randomized clinical trial in China showed reteplase was well tolerated in patients with acute ischemic stroke within 4.5 hours of onset with a similar efficacy profile to alteplase.[278] There were no statistically significant differences for the rate of death and symptomatic intracranial hemorrhage (sICH) in the low-dose reteplase group, the high-dose reteplase group, and the alteplase group.[278] One phase 3 prospective noninferiority trial, also in China, found that reteplase was more likely than alteplase to result in an excellent functional outcome (defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days post-stroke in patients within 4.5 hours from symptoms onset.[279] The incidence of adverse events and any intracranial hemorrhage at 90 days was higher with reteplase than with alteplase but the incidence of death and symptomatic intracranial hemorrhage within 36 hours after disease onset was similar in both groups.[279]

Recombinant prourokinase (rhPro-UK)

rhPro-UK is a novel thrombolytic agent which acts as a specific plasminogen activator. One phase 3 randomized controlled trial in China found that rhPro-UK was noninferior to alteplase within 4.5 hours after stroke onset for achieving excellent functional outcomes, with no difference between groups in safety endpoints.[280] The rhPro-UK group showed a similar rate of sICH but fewer cases of systemic bleeding than the alteplase group.[280] The frequency of sICH within 36 hours was lower in the t rhPro-UK group than in the alteplase group.[281] All-cause mortality within 7 days did not differ between groups.[281] rhPro-UK is approved in China for the management of MI, but it is not available in other countries as yet.

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.[282][283] Edaravone is not approved for ischemic stroke in the US nor Europe.

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 Food and Drug Administration (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.[284]

Cilostazol

This is an emerging option in acute ischemic stroke that is comparable to aspirin in its efficacy and safety.[285][286] [ ] 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.[287] 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.[113]

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.[129]

Tirofiban

Tirofiban, a glycoprotein IIb/IIIa inhibitor, inhibits platelet function through its blocking the linkage of platelets to fibrinogen.[41] In the RESCUE BT trial, tirofiban showed no benefit when given before intra-arterial thrombectomy to treat large vessel occlusion within 24 hours of onset.[288] However, in the RESCUE BT 2 trial, tirofiban for 2 days showed a greater likelihood of an excellent outcome than low-dose aspirin, with a slightly higher intracerebral hemorrhage when treating non-large or medium vessel occlusion strokes in the following four situations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24-96 hours after onset; early neurologic deterioration after thrombolysis; thrombolysis with no improvement at 4-24 hours.[289]