By Matthew E. Fink, MD
Louis and Gertrude Feil Professor and Chair, Department of Neurology, Associate Dean for Clinical Affairs, New York Presbyterian/Weill Cornell Medical College
SOURCE: Wang D, Gao C, Xu X, et al. Treatment of chronic subdural hematoma with atorvastatin combined with low-dose dexamethasone: Phase II randomized proof-of-concept clinical trial. J Neurosurg 2020; Jan 31:1-9. doi: 10.3171/2019.11.jns192020. [Online ahead of print].
Chronic subdural hematoma is a common cause of serious neurological morbidity and mortality in the elderly population and is increasing in prevalence as the result of the aging population and the increasing use of antithrombotic medications. Surgical intervention has been the standard of care, but it carries a significant risk of recurrence and complications (20%). Various drug treatments have been proposed and tried. In recent years, treatment with atorvastatin has been shown to be beneficial in several small, randomized trials. Atorvastatin has both an anti-inflammatory effect and the ability to mobilize endothelial progenitor cells, which assist in vascular repair. The current investigators proposed that adding a low dose of dexamethasone to atorvastatin treatment might enhance the anti-inflammatory benefits without causing the side effects associated with high doses of corticosteroids.
Sixty patients with chronic subdural hematoma were randomized to one of two treatment protocols. Group 1 received a five-week regimen of atorvastatin 20 mg daily, and group 2 received a five-week regimen of atorvastatin 20 mg daily plus dexamethasone starting at 2.25 mg daily for two weeks, followed by 0.75 mg twice a day for two weeks, and then 0.75 mg once a day for one week. The primary endpoint was hematoma reduction assessed by imaging at five weeks of follow-up. Secondary outcomes included neurological improvements. The mean age of patients was 66.6 years, and 25% of the patients were women. Patients treated with a combination of atorvastatin plus dexamethasone had more hematoma reduction by the fifth week compared to the group treated with atorvastatin alone. This difference was noted from the second week onward and persisted until the 12th week of follow-up. Complete recovery of neurological function at five weeks was achieved an 83.3% of patients treated with combination therapy of atorvastatin plus dexamethasone, compared to 32.1% of patients treated with atorvastatin alone. In addition, the investigators measured and identified higher levels of regulatory T-cells and endothelial progenitor cells in the peripheral blood of patients treated with the combination therapy. In this Phase II trial, combination therapy with atorvastatin and dexamethasone appeared to be better than atorvastatin alone, and justifies a larger, Phase III randomized trial with a placebo-controlled arm.