title: Uric acid therapy improves the outcomes of stroke patients treated with intravenous tissue plasminogen activator and mechanical thrombectomy.
abstract: Background Numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischemic stroke, making the search for new treatments imperative. Uric acid is an endogenous antioxidant making it a drug candidate to improve stroke outcomes. Aim To report the effects of uric acid therapy in stroke patients receiving intravenous thrombolysis and mechanical thrombectomy. Methods Forty-five patients with proximal vessel occlusions enrolled in the URICO-ICTUS trial received intravenous recombinant tissue plasminogen activator within 4.5 h after stroke onset and randomized to intravenous 1000 mg uric acid or placebo (NCT00860366). These patients also received mechanical thrombectomy because a brain computed tomogaphy angiography confirmed the lack of proximal recanalization at the end of systemic thrombolysis. The primary outcome was good functional outcome at 90 days (modified Rankin Score 0-2). Safety outcomes included mortality, symptomatic intracerebral bleeding, and gout attacks. Results The rate of successful revascularization was >80% in the uric acid and the placebo groups but good functional outcome was observed in 16 out of 24 (67%) patients treated with uric acid and 10 out of 21 (48%) treated with placebo (adjusted Odds Ratio, 6.12 (95% CI 1.08-34.56)). Mortality was observed in two out of 24 (8.3%) patients treated with uric acid and one out of 21 (4.8%) treated with placebo (adjusted Odds Ratio, 3.74 (95% CI 0.06-226.29)). Symptomatic cerebral bleeding and gout attacks were similar in both groups. Conclusions Uric acid therapy was safe and improved stroke outcomes in stroke patients receiving intravenous thrombolysis followed by thrombectomy. Validation of this simple strategy in a larger trial is urgent.
authors.affiliation: 1 Hospital Clinic, Barcelona, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Chamorro
authors.affiliation: 1 Hospital Clinic, Barcelona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Amaro
authors.affiliation: 2 Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Castellanos
authors.affiliation: 3 Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Gomis
authors.affiliation: 1 Hospital Clinic, Barcelona, Spain.
authors.forename: Xabier
authors.initials: X
authors.lastname: Urra
authors.affiliation: 1 Hospital Clinic, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Blasco
authors.affiliation: 4 Hospital Universitario of Valladolid, Valladolid, Spain.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Arenillas
authors.affiliation: 1 Hospital Clinic, Barcelona, Spain.
authors.forename: Luis S
authors.initials: LS
authors.lastname: Román
authors.affiliation: 5 Hospital of Navarra, Pamplona, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Muñoz
authors.affiliation: 1 Hospital Clinic, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Macho
authors.affiliation: 6 Hospital Parc Taulí, Sabadell, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Cánovas
authors.affiliation: 7 Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Marti-Fabregas
authors.affiliation: 8 University of Iowa Carver College of Medicine, Iowa City, USA.
authors.forename: Enrique C
authors.initials: EC
authors.lastname: Leira
authors.affiliation: 9 Institute for Biomedical Research of Barcelona (IIBB), Barcelona, Spain.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Planas
mesh_terms: D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000628:therapy*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000628:therapy*; D017131:Thrombectomy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D014527:Uric Acid / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D014527:Uric Acid; D010959:Tissue Plasminogen Activator
keywords: Antioxidants; cerebral ischemia; reperfusion; revascularization; stroke