Atorvastatin was found to not affect symptomatic hemorrhage caused by CCM, but the trial paved the way for future CCM drug trials
DOES ATORVASTATIN STABILIZE CCM LESIONS THAT HAVE RECENTLY BLED?
Atorvastatin, a widely available drug commonly used to treat high blood pressure, does not affect rebleeding in CCM patients who had had a symptomatic hemorrhage in the previous year, according to study findings published in the April 2025 edition of Lancet Neurology.
HOW DID THIS STUDY ADVANCE CCM DRUG RESEARCH?
The trial answered the pressing question of whether atorvastatin could stabilize CCM lesions that had recently bled, and it also pioneered the use of a novel measurement tool, quantitative susceptibility mapping (QSM), to determine atorvastatin’s efficacy. QSM is an advanced MRI technique that measures an important biomarker – the amount of iron around CCM lesions in the brain. Iron is present when a lesion has recently bled. Using QSM allowed researchers to answer the study’s main question quickly and objectively. This tool can now be used in future trials, ultimately speeding up the timeline to better treatments and a cure for CCM.
View Dr. Awad’s webinar in which he reports the trial results.
WHAT ABOUT OTHER DRUG RESEARCH, ESPECIALLY ROCK INHIBITORS?
The Atorvastatin Therapy in Cavernous Angiomas with Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial was conducted at the University of Chicago from 2018 to 2022. It was the first trial to assess whether a drug known to inhibit Rho-Kinase (ROCK), a protein involved in CCM hemorrhage, could stabilize lesion bleeding in CCM patients.
Additional trials that test ROCK inhibitors’ effect on CCM continue to be an important area of CCM treatment research. In preclinical studies, ROCK inhibitors decrease CCM lesion size, number, and bleeding. According to the Lancet Neurology article’s authors, “drugs with stronger and more specific ROCK inhibition properties than atorvastatin might be needed to see a meaningful benefit.” At least three pharmaceutical companies currently are developing ROCK inhibitors specifically to treat CCM disease.
THANK YOU TO OUR CCM DRUG PIONEERS
The Alliance to Cure Cavernous Malformation is grateful for the leadership of the University of Chicago and the hundreds of CCM patients who volunteered their time to enroll in this trial. Together, we are driving a cure.
Reference
Prof Issam A Awad MD, Roberto J Alcazar-Felix MD, Agnieszka Stadnik MS, Serena Kinkade BS, Aditya Jhaveri BS, Justine Lee BSN, Stephanie Hage MD, Javed Iqbal MBBS, Sean P Polster MD, Robert Shenkar PhD, Kevin Treine BA, Nichol McBee MPH, Noeleen Ostapkovich MS, Karen Lane CCRP, Prof James K Liao MD, Prof Matthew Sorrentino MD, Cornelia Lee PsyD, Prof Kelly D Flemming MD, Romuald Girard PhD, Prof Timothy J Carroll PhD, Prof Daniel F Hanley MD.Safety and efficacy of atorvastatin for rebleeding in cerebral cavernous malformations (AT CASH EPOC): a phase 1/2a, randomised placebo-controlled trial.The Lancet Neurology. Volume 24, Issue 4, April 2025, Pages 295-304. https://doi.org/10.1016/S1474-4422(25)00036-5
Last update 4.10.25
