Safety and efficacy of atorvastatin for rebleeding in cerebral cavernous malformations (AT CASH EPOC): a phase 1/2a, randomised placebo-controlled trial
Abstract
Background. Cerebral cavernous malformations (CCMs) carry a high risk of rebleeding after symptomatic haemorrhage, with serious clinical sequelae. Atorvastatin was shown to prevent CCM growth and bleeding in animal models. We aimed to assess the safety and efficacy of atorvastatin on rebleeding in patients with CCM after a symptomatic haemorrhage. Methods. We did a phase 1/2a randomised trial at the University of Chicago’s CCM Center of Excellence. Patients aged 18–80 years with untreated CCMs who had experienced symptomatic bleeding from a CCM lesion within the previous year were eligible. We randomly allocated patients (1:1) to oral atorvastatin (80 mg daily for 2 years) or matching placebo. The primary efficacy outcome was mean percent change in lesional iron deposition per year, measured by quantitative susceptibility mapping (QSM) on MRI and averaged over 2 years; a decrease would signal potential benefit and an increase a safety concern. The primary efficacy outcome was analysed by modified intention to treat, including patients with at least one annual paired QSM assessment. Safety outcomes included rates of bleeds and serious adverse events necessitating drug discontinuation. This trial is registered at ClinicalTrials.gov, NCT02603328, and is completed. Findings. Between July 25, 2018, and July 22, 2022, 326 patients were assessed for eligibility, and 80 patients were allocated either atorvastatin (n=41) or placebo (n=39). 29 patients were male and 51 were female. 64…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 80 participants or records.
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