Long-acting statin for aneurysmal subarachnoid hemorrhage: A randomized, double-blind, placebo-controlled trial

J Cereb Blood Flow Metab. 2018 Jul;38(7):1190-1198. doi: 10.1177/0271678X17724682. Epub 2017 Aug 1.

Abstract

Statins have pleiotropic effects that are considered beneficial in preventing cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH). Many studies using statins have been performed but failed to show remarkable effects. We hypothesized that a long-acting statin would be more effective, due to a longer half-life and stronger pleiotropic effects. Patients with aSAH were randomly assigned to a pitavastatin group (4 mg daily; n = 54) and a placebo group ( n = 54) after repair of a ruptured aneurysm. The primary efficacy end point was vasospasm-related delayed ischemic neurological deficits (DIND), and the secondary end points were cerebral vasospasm evaluated by digital subtraction angiography (DSA), vasospasm-related new cerebral infarctions, and outcome at three months. Severe cerebral vasospasms on DSA were statistically fewer in the pitavastatin group than in the placebo group (14.8% vs. 33.3%; odds ratio, 0.32; 95% confidence interval, 0.11-0.87, p = 0.042); however, the occurrence of DIND and new infarctions and outcome showed no statistically significant differences between the groups. The present study is the first to prove the definite, statin-induced amelioration of cerebral vasospasm on DSA. However, administration of any type of statin at the acute phase of aSAH is not recommended.

Keywords: Subarachnoid hemorrhage; angiography; clinical trials; randomized controlled trials; vasospasm.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aneurysm, Ruptured / diagnostic imaging
  • Aneurysm, Ruptured / drug therapy*
  • Aneurysm, Ruptured / pathology
  • Aneurysm, Ruptured / physiopathology
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / adverse effects
  • Double-Blind Method
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Intracranial Aneurysm / diagnostic imaging
  • Intracranial Aneurysm / drug therapy*
  • Intracranial Aneurysm / physiopathology
  • Male
  • Middle Aged
  • Quinolines / administration & dosage*
  • Quinolines / adverse effects
  • Subarachnoid Hemorrhage / diagnostic imaging
  • Subarachnoid Hemorrhage / drug therapy*
  • Subarachnoid Hemorrhage / pathology
  • Subarachnoid Hemorrhage / physiopathology
  • Vasospasm, Intracranial / diagnostic imaging
  • Vasospasm, Intracranial / drug therapy*
  • Vasospasm, Intracranial / physiopathology

Substances

  • Delayed-Action Preparations
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Quinolines
  • pitavastatin

Associated data

  • UMIN-CTR/UMIN000015977