Trial reportThe Lancet. Neurology2025
Safety and efficacy of atorvastatin for rebleeding in cerebral cavernous malformations (AT CASH EPOC): a phase 1/2a, randomised placebo-controlled trial.
Trial report in The Lancet. Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02603328 (Phase I-II Randomized, Placebo-Controlled, Single-Blinded, Single-Site Clinical Trial of Atorvastatin in the Treatment of Cavernous Angiomas With Symptomatic Hemorrhage Exploratory Proof of Concept), which is not on this map. Cited by 8 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase I-II Randomized, Placebo-Controlled, Single-Blinded, Single-Site Clinical Trial of Atorvastatin in the Treatment of Cavernous Angiomas With Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC)
Who cites it
8 citing papers in PubMed.
- Recurrent Symptomatic Hemorrhage in Cerebral Cavernous Malformations After Discontinuation of Atorvastatin or Placebo.Journal of the American Heart Association · 2026Trial
- MicroRNA-21-3p regulation of NADPH oxidase 4 and vascular endothelial growth factor A contributes to hemorrhage in cerebral cavernous malformations.Non-coding RNA research · 2026Article
- Rapamycin Partially Reverts Cavernoma Endothelial Cell Phenotype and, When Combined With Lapatinib, Ameliorates Chronic Lesions.Journal of cellular and molecular medicine · 2026Article
- Carrier free oral Co-delivery of atorvastatin via baicalein-copper-network for atherosclerosis therapy through senescence reversal and multi-mechanistic synergy.Bioactive materials · 2026Article
- Functional and Patient-Reported Outcomes in the Atorvastatin versus Placebo Trial of Hemorrhagic Cerebral Cavernous Malformations: An Exploratory Study.Cerebrovascular diseases (Basel, Switzerland) · 2026Article
- Familial Cerebral Cavernous Malformations: Pathophysiology, Genetics, Biomarkers, and Treatment Perspectives.Journal of neurochemistry · 2026Review
- The effect of statins on the risk of bleeding in cerebral cavernous malformations: A systematic review and meta-analysis.Surgical neurology international · 2026Review
- Relationship between impaired cerebral lymphatic function and iron deposition, blood flow in VaD: a clinical MRI study.Frontiers in neuroscience · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors.
Funding
Abstract
backgroundCerebral 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 CCMs after a symptomatic haemorrhage.
methodsWe 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 had symptomatic bleeding from a CCM lesion within the previous year were eligible. Patients were randomly allocated (1:1) to oral atorvastatin (80 mg daily for 2 years) or matching placebo. Investigators, clinical staff, and participants were masked to the assigned treatment. The primary efficacy outcome was the percentage change in mean 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 in the modified intention-to-treat cohort, 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.
findingsBetween 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 (36%) patients were male and 51 (64%) were female. 64 (80%) patients (33 in the atorvastatin group and 31 in the placebo group) had at least one annual paired QSM assessment and were included in the modified intention-to-treat analyses. The mean annual percentage change in lesional QSM was 10·88 (SE 7·29) with atorvastatin versus 12·09 (SE 7·54) with placebo (treatment effect -1·22, 95% CI -22·25 to 19·81; p=0·91). Symptomatic haemorrhage was reported in six patients assigned atorvastatin and seven patients assigned placebo (relative risk 0·81, 95% CI 0·31 to 2·13). No patients had a serious adverse event requiring drug discontinuation and no deaths were recorded.
interpretationFor people with symptomatic haemorrhage caused by CCMs, atorvastatin did not affect the mean change in lesional iron deposition on brain MRI over 2 years when compared with placebo. Atorvastatin was well tolerated and no safety concerns were noted. The study provides a useful framework for biomarker driven drug assessment in a rare disease.
fundingUS National Institutes of Health.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.