A Prospective Safety Trial of Atorvastatin Treatment to Assess Rebleeding after Spontaneous Intracerebral Hemorrhage: A Serial MRI Investigation

AIM: This study was designed to determine any rebleeding after atorvastatin treatment following spontaneous intracerebral hemorrhage (ICH) in a prospective safety trial.PATIENTS: Atorvastatin (80 mg/day) therapy was initiated in 6 patients with primary ICH with admission Glasgow Coma Score (GCS) >5 within 24 hours of ictus and continued for 7 days, with the dose tapered and treatment terminated over the next 5 days. Patients were studied longitudinally by multiparametric magnetic resonance imaging (MRI) at three time points: acute (3 to 5 days), subacute (4 to 6 weeks) and chronic (3 to 4 months). Imaging sequences included T1, T2-weighted imaging (T2WI), diffusion tensor imaging (DTI) and contrast-enhanced MRI measures of cerebral perfusion, blood volume and blood-brain barrier (BBB) permeability. Susceptibility weighted imaging (SWI) was used to identify primary ICH and to check for secondary rebleeding. Final outcome was assessed using Glasgow Outcome Score (GOS) at 3-4 months.RESULTS: Mean admission GCS was 13.2±4.0 and mean GOS at 3 months was 4.5±0.6. Hemorrhagic lesions were segmented into core and rim areas. Mean lesion volumes decreased significantly between the acute and chronic study time points (p=0.008). Average ipsilateral hemispheric tissue loss at 3 to 4 months was 11.4±4.6 cm3. MRI showed acutely reduced CBF (p=0.004) and CBV (p=0.002) in the rim, followed by steady normalization. Apparent diffusion coefficient of water (ADC) in the rim demonstrated no alterations at any of the time points (p>0.2). The T2 values were significantly elevated in the rim acutely (p=0.02), but later returned to baseline. The ICH core showed sustained low CBF and CBV values concurrent with a small reduction in ADC acutely, but significant ADC elevation at the end suggestive of irreversible injury.CONCLUSION: Despite the presence of a small, probably permanent, cerebral lesion in the ICH core, no patients exhibited post-treatment rebleeding. These data suggest that larger, Phase 2 trials are warranted to establish long term clinical safety of atorvastatin in spontaneous ICH.