Combination of Thrombolysis and Statins in Acute Stroke Is Safe: Results of the STARS Randomized Trial (Stroke Treatment With Acute Reperfusion and Simvastatin)

Stroke. 2016 Nov;47(11):2870-2873. doi: 10.1161/STROKEAHA.116.014600. Epub 2016 Oct 6.

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.

Keywords: clinical trial; neuroprotection; simvastatin; stroke; thrombolysis.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Brain Ischemia / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Simvastatin / administration & dosage
  • Simvastatin / adverse effects
  • Simvastatin / pharmacology*
  • Stroke / drug therapy*
  • Tissue Plasminogen Activator / administration & dosage
  • Tissue Plasminogen Activator / adverse effects
  • Tissue Plasminogen Activator / pharmacology*

Substances

  • Fibrinolytic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin
  • Tissue Plasminogen Activator

Associated data

  • ClinicalTrials.gov/NCT01073007