Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese Patients

Abstract

IMPORTANCE Chronic subdural hematoma (CSDH) is a trauma-associated condition commonly found in elderly patients. Surgery is currently the treatment of choice, but it carries a significant risk of recurrence and death. Nonsurgical treatments remain limited and ineffective. Our recent studies suggest that atorvastatin reduces hematomas and improves the clinical outcomes of patients with CSDH.OBJECTIVE To investigate the safety and therapeutic efficacy of atorvastatin to nonsurgically treat patients with CSDH. DESIGN, SETTING, AND PARTICIPANTSThe Effect of Atorvastatin on Chronic Subdural Hematoma (ATOCH) randomized, placebo-controlled, double-blind phase II clinical trial was conducted in multiple centers in China from February 2014 to November 2015. For this trial, we approached 254 patients with CSDH who received a diagnosis via a computed tomography scan; of these, 200 (78.7%) were enrolled because 23 patients (9.1%) refused to participate and 31 (12.2%) were disqualified.INTERVENTIONS Patients were randomly assigned to receive either 20 mg of atorvastatin or placebo daily for 8 weeks and were followed up for an additional 16 weeks. MAIN OUTCOMES AND MEASURESThe primary outcome was change in hematoma volume (HV) by computed tomography after 8 weeks of treatment. The secondary outcomes included HV measured at the 4th, 12th, and 24th weeks and neurological function that was evaluated using the Markwalder grading scale/Glasgow Coma Scale and the Barthel Index at the 8th week.RESULTS One hundred ninety-six patients received treatment (169 men [86.2%]; median [SD] age, 63.6 [14.2] years). The baseline HV and clinical presentations were similar between patients who were taking atorvastatin (98 [50%]) and the placebo (98 [50%]). After 8 weeks, the HV reduction in patients who were taking atorvastatin was 12.55 mL more than those taking the placebo (95% CI, 0.9-23.9 mL; P = .003). Forty-five patients (45.9%) who were taking atorvastatin significantly improved their neurological function, but only 28 (28.6%) who were taking the placebo did, resulting in an adjusted odds ratio of 1.957 for clinical improvements (95% CI, 1.07-3.58; P = .03). Eleven patients (11.2%) who were taking atorvastatin and 23 (23.5%) who were taking the placebo underwent surgery during the trial for an enlarging hematoma and/or a deteriorating clinical condition (hazard ratio, 0.47; 95% CI, 0.24-0.92; P = .03). No significant adverse events were reported.CONCLUSIONS AND RELEVANCE Atorvastatin may be a safe and efficacious nonsurgical alternative for treating patients with CSDH.

Treatment of Relapsed Chronic Subdural Hematoma in Four Young Children with Atorvastatin and Low‐dose Dexamethasone

“…[13][14][15][16][17][18] This treatment of pediatric CSDH patients with ATO was originated from the placebo-controlled double-blind phase II trial (ATOCH trial), showing that ATO is safe and effective in nonsurgically treated adults with CSDH during 8 weeks of treatment and 12 weeks of followup. 6 Patients who received ATO had significantly reduced hematoma volume and improved neurologic function, as compared with placebotreated patients. ATO appears to be more effective for older patients and/or those with larger hematoma.…”

“…Although not fully comparable, the volume reduction in hematoma was observed within 2 weeks after the treatment was initiated and was shorter than that of adult CSDH patients on ATO monotherapy. 6 No severe complications were related to ATO and DXM ( Table 1). These results suggest that this combined therapy may be effective for pediatric patients with relapsing CSDH, without severe complications associated with high doses or long-term use of ATO and DXM in children, as previously reported in the literature.…”

“…improving the neurologic dysfunction of adult patients. 6 ATO at 5-10 mg/day was used to treat pediatric patients with hyperlipidemia, 7,8 suggesting that ATO is safe for pediatric patients. In addition, dexamethasone (DXM) at 12 mg/day was also shown to be effective in reducing CSDH but may exhibit severe side effects such as dyspepsia, shortness of breath, muscle weakness, and fatigue.…”

“…The ATO dosage was not based on body weight but developed based on the trial on adult patients with CSDH for ATO. 6 DXM was also not based on body weight (although the body weight of the patients is provided in Table 1) because there is no clinical standard for treating pediatric patients with CSDH. The maximal dosing at 1.125 mg/day for the first week was chosen on the basis of a DXM-suppressing test.…”

Construction of lncRNA‐associated ceRNA networks to identify prognostic lncRNA biomarkers for glioblastoma

“…Some traditional medicines have been newly discovered to have therapeutic effects, and it is possible to understand their pharmacological effects in a faster manner, which would facilitate their early application in clinical settings. These drugs include atorvastatin, which is regarded as a synthetic lipid‐lowering agent and has been found to have a significant therapeutic effect on a chronic subdural hematoma in recent years 34 …”