What new thrombolytic therapies following a stroke are being investigated?

Answer

Additional promising thrombolytic strategies investigated in pilot trials include the following:

Combined intravenous and intra-arterial thrombolysis, bringing together the speed of initiation of IV and the higher recanalization rates of IA^[34]
Combined IV and/or IA thrombolysis with endovascular mechanical clot retrieval or aspiration, joining the ability of mechanical devices to dispose of large proximal clot burdens with the ability of lytics to initiate therapy early (IV lysis) or clean up smaller occlusions in distal arteries not accessible to mechanical attack (IA lysis)^[35]
Ultrasonography-enhanced thrombolysis, using high-frequency ultrasonography to accelerate enyzymatic fibrinolysis by increasing penetration of drug molecules into the clot^[36]

A prospective, observational study by Alonso de Lecinana et al indicated that in patients with large vessel occlusion stroke in whom, owing to comorbidities, intravenous thrombolysis is contraindicated, primary mechanical thrombectomy is a safe alternative. The study involved 131 patients with large vessel occlusion who were treated within 4.5 hours of symptom onset, including 21 contraindicated patients who received primary mechanical thrombectomy and 110 patients without contraindications who received intravenous thrombolysis. Fifty-three patients in the latter group subsequently received mechanical thrombectomy, because the occlusion persisted. No patients in the primary mechanical thrombectomy group had symptomatic intracranial hemorrhage, compared with 6% (three patients) in the intravenous thrombolysis plus intravenous thrombectomy group. Mortality rates in the two groups were 14% (3 patients) and 4% (2 patients), respectively.^[37]

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Media Gallery

The bar graphs show the percent of patients with different outcomes on the modified Rankin Scale of global disability 3 months following treatment with tPA or placebo in the NINDS-tPA Trials 1 and 2. Rankin 0 = no symptoms; 1 = No significant disability, despite symptoms; able to perform all usual duties and activities; 2 = Slight disability; unable to perform all previous activities but able to look after own affairs without assistance; 3 = Moderate disability; requires some help, but able to walk without assistance; 4 = Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5 = Severe disability; bedridden, incontinent, and requires constant nursing care and attention; 6 = Dead. Image courtesy of UCLA Stroke Center.
Visual decision aid to help patients and families assess benefits and risks of thrombolytic therapy within the first 3 hours of onset. Image publicly available under a Creative Commons Use with Attribution license.
Thrombolytic therapy carries a small, but significant, risk of life-threatening hemorrhage. For this reason, it is important to carefully screen for exclusionary criteria prior to administering t-PA, including hemorrhage, large areas of infarction and patient presentation beyond the 3-hour window for IV t-PA or possibly beyond 6 hours for IA TPA. This case illustrates this point in a patient with normal NCCT who was treated with IV t-PA for acute stroke and over the next 2 days, developed significant hemorrhage. Hemorrhage is noted to progressively increase in size along the medial margin of the right thalamus and the third ventricle. There is obstructive hydrocephalus with hemorrhage layering in the dependent portions of the occipital horns.
This 48-year-old male presented with acute left-sided hemiplegia, facial palsy, and right-sided gaze preference. Angiogram with selective injection of the right internal carotid artery demonstrates occlusion of the M1 segment of the right MCA and A2 segment of the right ACA. Image courtesy of Concentric Medical.
Follow-up imaging in the same patient as in the previous image after mechanical embolectomy demonstrates complete recanalization of the right middle cerebral artery and partial recanalization of the right A2 segment. Image courtesy of Concentric Medical.
Cerebral angiogram demonstrates an occlusion of the distal basilar artery in this 31-year-old male approximately 4.5 hours after symptom onset. Image courtesy of Concentric Medical.
Image on the left demonstrates deployment of a clot retrieval device in the same patient as in the previous image. Follow-up angiogram after embolectomy demonstrates recanalization of the distal basilar artery with filling of the superior cerebellar arteries and posterior cerebral arteries. The patient had complete resolution of symptoms following embolectomy. Image courtesy of Concentric Medical.

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Author

Jeffrey L Saver, MD, FAHA, FAAN Professor of Neurology, Director, UCLA Stroke Center, University of California, Los Angeles, David Geffen School of Medicine

Jeffrey L Saver, MD, FAHA, FAAN is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Neurological Association, National Stroke Association

Disclosure: Received the university of california regents receive funds for consulting services on clinical trial design provided to covidien, stryker, and lundbeck. from University of California for consulting.

Coauthor(s)

Mary Kalafut, MD Director, Stroke Center, Scripps Clinic, Green Hospital

Mary Kalafut, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Howard S Kirshner, MD Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital; Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center

Howard S Kirshner, MD is a member of the following medical societies: Alpha Omega Alpha, American Neurological Association, American Society of Neurorehabilitation, American Academy of Neurology, American Heart Association, American Medical Association, National Stroke Association, Phi Beta Kappa, Tennessee Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke Center

Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology, American Stroke Association

Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2; Physician Advisory Board for Coherex Medical; National Leader and Steering Committee Clinical Trial, Bristol Myers Squibb; Consultant, Abbott Vascular, Inc. .

Additional Contributors

Richard M Zweifler, MD Chief of Neurosciences, Sentara Healthcare; Professor and Chair of Neurology, Eastern Virginia Medical School

Richard M Zweifler, MD is a member of the following medical societies: American Academy of Neurology, American Stroke Association, Stroke Council of the American Heart Association, American Heart Association, American Medical Association

Disclosure: Nothing to disclose.

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