Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese Patients: A Randomized ClinicalTrial

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 participants: The 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 measures: The 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.

Trial registration: ClinicalTrials.gov Identifier: NCT02024373.

Figure 1.. Schematic Illustration of the Trial Protocol

CSDH indicates chronic subdural hematoma; CT, computed tomography.

Figure 2.. Changes in Hematoma Volume

Full analysis set (FAS) (A) and per protocol set (PPS) (B) methods were used to calculate the reduction in hematoma volume (HV) measured on the 4th and 8th weeks of treatment from the baseline (BL) measurements. C and D, The trend lines for the change in HV over time. The data are presented as medians and quartiles and were analyzed using the Wilcoxon test for FAS (A and C, n = 98 for each group) and PPS (B and D, n = 81 for atorvastatin and n = 90 for placebo).

Figure 3.. Neurological Function and Rate of Surgery

A, The Markwalder grading scale/Glasgow Coma Scale (MGS-GCS) was used to evaluate the effect of atorvastatin on improving the neurological function of patients with chronic subdural hematoma (scores were measured on the eighth week of treatment) (Wilcoxon test, n = 98). B, Patients were switched to surgery because of increasing hematoma volume and/or deteriorating neurological symptoms (log-rank test, n = 196; hazard ratio, 0.47; 95% CI, 0.24-0.92; P = .03).