Bleeding risk of cerebral cavernous malformations in patients on β-blocker medication: a cohort study

OBJECTIVE Cerebral cavernous malformations (CCMs) are frequently diagnosed vascular malformations of the brain. Although most CCMs are asymptomatic, some can be responsible for intracerebral hemorrhage or seizures. In selected cases, microsurgical resection is the preferred treatment option. Treatment with the unselective beta-blocker propranolol has been presumed to stabilize and eventually lead to CCM size regression in a limited number of published case series; however, the underlying mechanism and evidence for this effect remain unclear. The aim of this study was to investigate the risk for CCM-related hemorrhage in patients on long-term beta-blocker medication. METHODS A single-center database containing data on patients harboring CCMs was retrospectively interrogated for a time period of 35 years. The database included information about hemorrhage and antihypertensive medication. Descriptive and survival analyses were performed, focusing on the risk of hemorrhage at presentation and during follow-up (first or subsequent hemorrhage) in patients on long-term beta-blocker medication versus those who were not. Follow-up was censored at the first occurrence of new hemorrhage, surgery, or the last clinical review. For purposes of this analysis, the beta-blocker group was divided into the following main subgroups: any beta-blocker, beta 1-selective beta-blocker, and any unselective beta-blocker. RESULTS Of 542 CCMs among 408 patients, 81 (14.9%) were under treatment with any beta-blocker; 65 (12%) received beta 1-selective beta-blocker, and 16 (3%) received any unselective beta-blocker. One hundred thirty-six (25.1%) CCMs presented with hemorrhage at diagnosis. None of the beta-blocker groups was associated with a lower risk of hemorrhage at the time of diagnosis in a univariate descriptive analysis (any beta-blocker: p = 0.64, beta 1-selective: p = 0.93, any unselective beta-blocker: p = 0.25). Four hundred ninety-six CCMs were followed up after diagnosis and included in the survival analysis, for a total of 1800 lesion-years. Follow-up hemorrhage occurred in 36 (7.3%) CCMs. Neither univariate descriptive nor univariate Cox proportional-hazards regression analysis showed a decreased risk for follow-up hemorrhage under treatment with beta-blocker medication (any beta-blocker: p = 0.70, HR 1.19, 95% CI 0.49-2.90; beta 1-selective: p = 0.78, HR 1.15, 95% CI 0.44-3.00; any unselective beta-blocker: p = 0.76, HR 1.37, 95% CI 0.19-10.08). Multivariate Cox proportional-hazards regression analysis including brainstem location, hemorrhage at diagnosis, age, and any beta-blocker treatment showed no reduced risk for follow-up hemorrhage under any beta-blocker treatment (p = 0.53, HR 1.36, 95% CI 0.52-3.56). CONCLUSIONS In this retrospective cohort study, beta-blocker medication does not seem to be associated with a decreased risk of CCM-related hemorrhage at presentation or during follow-up.