Rajbeer Singh Sangha, MD

Wong GKC, Chan DYC, Siu DYW, Zee BCY, Poon WS, Chan MTV, et al. High-Dose Simvastatin for Aneurysmal Subarachnoid Hemorrhage: Multicenter Randomized Controlled Double-Blinded Clinical Trial. Stroke. 2014

The authors of this study delved into a subject that has been of much discussion as of late. Following aneurysmal SAH, 18–56% of patients demonstrate evidence of secondary ischemia with clinical deterioration, which is also known as delayed ischemic deficit (DID). Statins amongst its many functions has been known to improve endothelial vasomotor function, increase nitric oxide bioavailability, possess antioxidant properties, counter thrombus formation, induce angiogenesis, endogenous cell proliferation and neurogenesis, induce vascular stabilization and suppress cytokine responses during cerebral ischemia. All of these factors in theory work to stabilize the cerebrovascular system following injury. 

Two randomized, placebo-controlled pilot trials that used the highest clinically approved dose of simvastatin (80 mg daily) gave positive results despite a lower dose of simvastatin (40mg daily) did not improve clinical outcomes. The STASH trial did not detect any benefit in the use of simvastatin for long-term or short-term outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). While no safety concerns were noted, it was concluded by the authors that statins should not be given during the acute period SAH. The objective of this study was to determine whether a high dose of simvastatin for the treatment of aneurysmal SAH is superior to a lower dose in terms of clinical outcomes and cost-effectiveness.

This study was an investigator-initiated, multicenter, randomized controlled trial with blinded outcome assessment performed at multiple centers in China. 255 patients were randomized to be in either the low dose simvastatin group or high dose simvastatin group. The results showed no difference was observed between the groups treated with the high dose or the lower dose of simvastatin in the incidence of DID (27% versus 24%; odds ratio, 1.2; 95% confidence interval, 0.7–2.0; p = 0.586). Furthermore, the two groups did not show difference in the rate of favorable outcomes (mRS 0–2) at 3 months (73% versus 72%; odds ratio, 1.1; 95% confidence interval, 0.6–1.9; p=0.770).

While the power in this study is limited, it further confirms what was found in the STASH trial and protocols should be amended given the evidence that is gathering that statins are not beneficial in terms of treatment in sub-arachnoid hemorrhage.