Bleeding Risk of Cerebral Cavernous Malformations in Patients on Beta Blocker Medication: A Cohort Study

Aim: 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 belongs to the preferred treatment options. Treatment with the unselective β-blocker propranolol has been presumed to stabilize and eventually lead to CCMs size regression in a limited number of published case series.^1–5 However, the underlying mechanism and the 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 β-blocker medication.

Methods: A retrospective single-center database containing data of 408 patients harboring 542 CCMs was interrogated for a time period of 35 years. Descriptive and survival analysis was performed, focusing on the risk of hemorrhage at presentation and during follow-up in patients on long-term β-blocker medication versus not. Follow-up was censored at the first occurrence of either new hemorrhage, surgery or last clinical review. β-blocker medication was divided in the following main subgroups: any β-blocker, β1-selective β-blocker, and any unselective β-blocker.

Results: Of 542 included CCMs, 81 (14.9%) were under a treatment with any β-blocker, 65 (12%) received β1-selective, and 16 (3%) any unselective β-blockers. One-hundred thirty-six (25.1%) CCMs presented with hemorrhage at diagnosis. None of the β-blocker subgroups was associated with a lower risk of hemorrhage at the time of diagnosis (any β-blocker [p = 0.64], β1-selective [p = 0.93], any unselective β-blocker [p = 0.25]). Four-hundred ninety-six CCMs were included into the survival analysis, for a total of 1,800 lesion-years. Follow-up hemorrhage occurred in 36 (7.3%) CCMs. β-blocker medication was not associated with a decreased risk of follow-up hemorrhage (any β-blocker [p = 0.70; hazard ratio, HR 1.19, 95% confidence interval, CI 0.49–2.90], β1-selective [p = 0.78; HR 1.15, 95% CI 0.44–3.00], any unselective β-blocker [p = 0.76; HR 1.37, 95% CI 0.19–10.08]). Multivariate cox proportional hazard regression including brain stem location, hemorrhage at diagnosis, age, and any β-blocker treatment showed no reduced risk of follow-up hemorrhage under any β-blocker treatment (p = 0.53; HR 1.36, 95% CI 0.52–3.56).

Conclusion: In this retrospective cohort study, β-blocker medication does not seem to be associated with a decreased risk of CCM-related hemorrhage at presentation or during follow-up.