Ongoing clinical study to evaluate benefits of high-dose simvastatin for patients with SAH

Can treatment with high doses of a cholesterol-lowering statin drug improve outcomes for patients with stroke caused by rupture and bleeding of brain aneurysms? An ongoing clinical trial will soon find out, according to an article in the May issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

Together with other research already underway, the trial will help to determine whether statin medications are effective in limiting damage to the brain in patients with aneurysmal subarachnoid hemorrhage (SAH). The lead investigator is Dr. George Kwok Chu Wong of Chinese University of Hong Kong.

Statins Show Promise in Treatment of Aneurysmal SAH
Dr. Wong and colleagues outline their plans for a study to evaluate the benefits of high-dose simvastatin for patients with SAH caused by a ruptured aneurysm. Subarachnoid hemorrhage is a life-threatening type of stroke in which there is bleeding into the brain. It most commonly occurs when an aneurysm—a weak spot in one of the blood vessels supplying the brain—ruptures or breaks.

Experimental studies, including preliminary studies in humans, have suggested that simvastatin may have treatment benefits for SAH. Statins have known "neuroprotective" effects in brain tissue. A recent summary of the evidence suggests that simvastatin—a widely prescribed cholesterol-lowering drug—can reduce brain injury caused by delayed ischemia (decreased blood flow). Delayed ischemia is a major contributor to death and disability after SAH.

Based on the evidence, statins have been recommended as part of routine treatment for aneurysmal SAH. "However," Dr. Wong and coauthors write, "no clinical data are available to answer whether a high-dose regimen is more effective than a normal-dose regimen, even though the biochemical actions and related neuroprotective mechanisms are thought to be dose-related."

Trial to Compare High vs Low Doses of Simvastatin
The planned study will compare high-dose versus low-dose simvastatin for patients with aneurysmal SAH. Both the higher and lower doses—80 and 40 milligrams per day—are commonly used in treating high cholesterol. Patients will be randomly assigned to either the higher or lower dose; treatment will start within 96 hours after stroke onset and continue for three weeks.

The main objective will be to see if there's any difference in the rate of delayed ischemia causing brain damage between groups. The study will also look for between-group differences in neurological function and disability, and evaluate the cost-effectiveness of high- versus low-dose simvastatin treatment. Safety assessment will include special attention to the risk of certain statin-related complications in the higher-dose group.

Dr. Wong and colleagues have been enrolling patients in their trial, and expect to have the results soon. They note that another trial is being conducted to compare normal-dose simvastatin with inactive placebo for patients with SAH after ruptured aneurysm. They conclude, " When the results are interpreted together, the research question of a possible beneficial effect of high-dose simvastatin in acute aneurysmal subarachnoid hemorrhage could be answered."

SOURCE Wolters Kluwer Health