High-dose Simvastatin for Aneurysmal Subarachnoid Haemorrhage: Is it Better?

Title: High-Dose Simvastatin for Aneurysmal Subarachnoid Haemorrhage (HDS-SAH): A multicentre randomised controlled double-blinded clinical trial.

Abstract

Background: Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid haemorrhage. Simvastatin is also a potent agent for reducing low-density lipoprotein (LDL). However, no clinical data are available to compare the efficacy of different dosage regimens (specifically, whether a high-dose regimen is more effective than a normal-dosage regimen) or conduct related cost-effectiveness analyses, even though the biochemical actions and related neuroprotective mechanisms are thought to be dosage-related. This gap in our knowledge of how to use statins and interpret trial results is very important, and motivated the investigators to conduct this study.

Objective: We hypothesized that eighty milligrams of simvastatin daily (high dose) over three weeks initiated within 96 hours of the ictus will reduce the incidence of delayed ischaemic deficits following subarachnoid haemorrhage when compared to 40mg of simvastatin daily (normal dose), leading to improvements in clinical outcomes and thus cost-effectiveness.

Methods: The study design is a randomised controlled double-blinded clinical trial (ClinicalTrials.gov Identifier: NCT01077206). Two hundred and forty aneurysmal subarachnoid haemorrhage patients (presenting within 96 hours of the ictus) from six neurosurgical centres are being recruited over three years. Primary outcome measure is Presence of delayed ischaemic deficits (DIDs). Secondary outcome measures include Modified Rankin Disability Score (mRS) at three months (favourable if 0-2) and Cost-Effectiveness Analysis in terms of overall direct cost per patient and incremental cost-effectiveness ratio (ICER).