Joan Montaner1, Alejandro Bustamante2, Silvia García-Matas2, Maite Martínez-Zabaleta2, Carmen Jiménez2, Javier de la Torre2, Francisco R Rubio2, Tomás Segura2, Jaime Masjuán2, David Cánovas2, Mar Freijo2, Raquel Delgado-Mederos2, Javier Tejada2, Aida Lago2, Yolanda Bravo2, Natália Corbeto2, Dolors Giralt2, Bárbara Vives-Pastor2, Anna de Arce2, Francisco Moniche2, Pilar Delgado2, Marc Ribó2. 1. From the Stroke Unit, Department of Neurology (J.M., M.R.), Neurovascular Research Laboratory, Institut de Recerca-Universitat Autónoma de Barcelona (J.M., A.B., N.C., D.G., P.D.), and Vall d' Hebron Institut d'Oncologia (S.G.-M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Neurovascular Unit, Department of Neurology, Hospital Universitario Donostia, Donostia-San Sebastian, Spain (M.M.-Z., A.A.); Department of Neurology, Hospital Universitari Son Espases, Palma de Mallorca, Spain (C.J., B.V.-P.); Stroke Program, Institute of Biomedicine of Seville, Hospital Universitario Virgen del Rocio, Seville, Spain (J.T., F.M.); Department of Neurology, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (F.R.R.); Department of Neurology, Hospital Universitario Virgen de la Victoria, Albacete, Spain (T.S.); Stroke Unit, Department of Neurology, IRYCIS, University Hospital Ramón y Cajal, Madrid, Spain (J.M.); Department of Neurology, Hospital Universitari Parc Tauli, Sabadell, Spain (D.C.); Department of Neurology, Hospital de Basurto, Bilbao, Spain (M.F.); Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain (R.D.-M.); Department of Neurology, Hospital Universitario de León, Spain (J.T.); Stroke Unit, Department of Neurology, Hospital Universitari la Fe, Valencia, Spain (A.L.); and Department of Neurology, Hospital Universitari General Yagüe, Burgos, Spain (Y.B.). joan.montaner@vhir.org. 2. From the Stroke Unit, Department of Neurology (J.M., M.R.), Neurovascular Research Laboratory, Institut de Recerca-Universitat Autónoma de Barcelona (J.M., A.B., N.C., D.G., P.D.), and Vall d' Hebron Institut d'Oncologia (S.G.-M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Neurovascular Unit, Department of Neurology, Hospital Universitario Donostia, Donostia-San Sebastian, Spain (M.M.-Z., A.A.); Department of Neurology, Hospital Universitari Son Espases, Palma de Mallorca, Spain (C.J., B.V.-P.); Stroke Program, Institute of Biomedicine of Seville, Hospital Universitario Virgen del Rocio, Seville, Spain (J.T., F.M.); Department of Neurology, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (F.R.R.); Department of Neurology, Hospital Universitario Virgen de la Victoria, Albacete, Spain (T.S.); Stroke Unit, Department of Neurology, IRYCIS, University Hospital Ramón y Cajal, Madrid, Spain (J.M.); Department of Neurology, Hospital Universitari Parc Tauli, Sabadell, Spain (D.C.); Department of Neurology, Hospital de Basurto, Bilbao, Spain (M.F.); Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain (R.D.-M.); Department of Neurology, Hospital Universitario de León, Spain (J.T.); Stroke Unit, Department of Neurology, Hospital Universitari la Fe, Valencia, Spain (A.L.); and Department of Neurology, Hospital Universitari General Yagüe, Burgos, Spain (Y.B.).
Abstract
BACKGROUND AND PURPOSE: The STARS trial (Stroke Treatment With Acute Reperfusion and Simvastatin) was conducted to demonstrate the efficacy and safety of simvastatin treatment in acute stroke. METHODS:STARS07 was a multicentre, phase IV, prospective, randomized, double-blind, placebo-controlled trial. Patients with Acute ischemic stroke recruited within 12 hours from symptom onset were randomized to oral simvastatin 40 mg or placebo, once daily for 90 days. Primary outcome was proportion of independent patients (modified Rankin Scale score of ≤2) at 90 days. Safety end points were hemorrhagic transformation, hemorrhagic events, death, infections, and serious adverse events. RESULTS:From April 2009 to March 2014, 104 patients were included. Fifty-five patients received intravenous tissue-type plasminogen activator. No differences were found between treatment arms regarding the primary outcome (adjusted odds ratio, 0.99 [0.35-2.78]; P=0.98). Concerning safety, no significant differences were found in the rate of hemorrhagic transformation of any type, nor symptomatic hemorrhagic transformation. There were no differences in other predefined safety outcomes. In post hoc analyses, for patients receiving tissue-type plasminogen activator, a favorable effect for simvastatin treatment was noted with higher proportion of patients experiencing major neurological recovery (adjusted odds ratio, 4.14 [1.18-14.4]; P=0.02). CONCLUSIONS:Simvastatin plus tissue-type plasminogen activator combination seems safe in acute stroke, with low rates of bleeding complications. Because of the low recruitment, the STARS trial was underpowered to detect differences in simvastatin efficacy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01073007.
RCT Entities:
BACKGROUND AND PURPOSE: The STARS trial (Stroke Treatment With Acute Reperfusion and Simvastatin) was conducted to demonstrate the efficacy and safety of simvastatin treatment in acute stroke. METHODS: STARS07 was a multicentre, phase IV, prospective, randomized, double-blind, placebo-controlled trial. Patients with Acute ischemic stroke recruited within 12 hours from symptom onset were randomized to oral simvastatin 40 mg or placebo, once daily for 90 days. Primary outcome was proportion of independent patients (modified Rankin Scale score of ≤2) at 90 days. Safety end points were hemorrhagic transformation, hemorrhagic events, death, infections, and serious adverse events. RESULTS: From April 2009 to March 2014, 104 patients were included. Fifty-five patients received intravenous tissue-type plasminogen activator. No differences were found between treatment arms regarding the primary outcome (adjusted odds ratio, 0.99 [0.35-2.78]; P=0.98). Concerning safety, no significant differences were found in the rate of hemorrhagic transformation of any type, nor symptomatic hemorrhagic transformation. There were no differences in other predefined safety outcomes. In post hoc analyses, for patients receiving tissue-type plasminogen activator, a favorable effect for simvastatin treatment was noted with higher proportion of patients experiencing major neurological recovery (adjusted odds ratio, 4.14 [1.18-14.4]; P=0.02). CONCLUSIONS:Simvastatin plus tissue-type plasminogen activator combination seems safe in acute stroke, with low rates of bleeding complications. Because of the low recruitment, the STARS trial was underpowered to detect differences in simvastatin efficacy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01073007.
Authors: Patrick T Ronaldson; Hrvoje Brzica; Wazir Abdullahi; Bianca G Reilly; Thomas P Davis Journal: J Pharmacol Exp Ther Date: 2020-11-09 Impact factor: 4.030