Bleeding Risk of Cerebral Cavernous Malformations in Patients on Statin and Antiplatelet Medication: A Cohort Study.

BACKGROUND: Statin medication has been identified as a potential therapeutic target for stabilizing cerebral cavernous malformations (CCMs). Although increasing evidence suggests that antiplatelet medication decreases the risk of CCM hemorrhage, data on statin medication in clinical studies are scarce. OBJECTIVE: To assess the risk of symptomatic CCM-related hemorrhage at presentation and during follow-up in patients on statin and antiplatelet medication. METHODS: A single-center database containing patients harboring CCMs was retrospectively analyzed over 41 years and interrogated for symptomatic hemorrhage at diagnosis, during follow-up, and statin and antiplatelet medication. RESULTS: In total, 212 of 933 CCMs (22.7%), harbored by 688 patients, presented with hemorrhage at diagnosis. Statin medication was not associated with a decreased risk of hemorrhage at diagnosis (odds ratio [OR] 0.63, CI 0.23-1.69, P = .355); antiplatelet medication (OR 0.26, CI 0.08-0.86, P = .028) and combined statin and antiplatelet medication (OR 0.19, CI 0.05-0.66; P = .009) showed a decreased risk. In the antiplatelet-only group, 2 (4.7%) of 43 CCMs developed follow-up hemorrhage during 137.1 lesion-years compared with 67 (9.5%) of 703 CCMs during 3228.1 lesion-years in the nonmedication group. No follow-up hemorrhages occurred in the statin and the combined statin and antiplatelet medication group. Antiplatelet medication was not associated with follow-up hemorrhage (hazard ratio [HR] 0.7, CI 0.16-3.05; P = .634). CONCLUSION: Antiplatelet medication alone and its combination with statins were associated with a lower risk of hemorrhage at CCM diagnosis. The risk reduction of combined statin and antiplatelet medication was greater than in patients receiving antiplatelet medication alone, indicating a possible synergistic effect. Antiplatelet medication alone was not associated with follow-up hemorrhage.

Antithrombotic medication and bleeding risk in patients with cerebral cavernous malformations: a cohort study.

OBJECTIVECerebral cavernous malformations (CCMs) are frequently diagnosed vascular abnormalities. The hemorrhagic risk associated with the use of long-term antithrombotic medication (ATM) in patients with CCMs is a matter of controversy. The aim of this study was to determine the hemorrhagic risk associated with ATM use in patients diagnosed with one or more CCMs.METHODSDemographic, clinical, treatment, and ATM-related information on patients diagnosed with one or more CCMs at a single institution over more than 34 years was retrospectively recorded. Univariate and multivariate descriptive and survival analyses were used to assess potential risk factors associated with CCM-related hemorrhage at presentation and during follow-up (first or subsequent hemorrhage).RESULTSA total of 408 patients were included in the analysis and 492 CCMs were followed up after diagnosis, for a total of 1616 lesion-years. Thirty-seven (7.5%) CCMs bled during follow-up, leading to an overall annual rate of CCM-related symptomatic hemorrhage of 2.3% (95% CI 1.7%-3.2%). Eighty-two patients harboring 91 CCMs (16.8%) were on ATM. When stratified for ATM, the annual rates of hemorrhage were 0.7% (95% CI < 0.01% to 4.2%) for the lesions in patients on ATM versus 2.5% (95% CI 1.8%-3.4%) for those not on ATM. ATM was not found to be associated with either an increased risk of CCM-related hemorrhage at presentation (p = 0.355) or an increased risk of CCM-related hemorrhage (first or subsequent hemorrhage) in multivariate descriptive (p = 0.912) and survival (p = 0.145) analyses.CONCLUSIONSThe use of ATM does not seem to be associated with an increased risk of hemorrhage in patients diagnosed with CCMs.

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

OBJECTIVECerebral 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 ß-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 ß-blocker medication.METHODSA 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 ß-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 ß-blocker group was divided into the following main subgroups: any ß-blocker, ß1-selective ß-blocker, and any unselective ß-blocker.RESULTSOf 542 CCMs among 408 patients, 81 (14.9%) were under treatment with any ß-blocker; 65 (12%) received ß1-selective ß-blocker, and 16 (3%) received any unselective ß-blocker. One hundred thirty-six (25.1%) CCMs presented with hemorrhage at diagnosis. None of the ß-blocker groups was associated with a lower risk of hemorrhage at the time of diagnosis in a univariate descriptive analysis (any ß-blocker: p = 0.64, ß1-selective: p = 0.93, any unselective ß-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 ß-blocker medication (any ß-blocker: p = 0.70, HR 1.19, 95% CI 0.49-2.90; ß1-selective: p = 0.78, HR 1.15, 95% CI 0.44-3.00; any unselective ß-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 ß-blocker treatment showed no reduced risk for follow-up hemorrhage under any ß-blocker treatment (p = 0.53, HR 1.36, 95% CI 0.52-3.56).CONCLUSIONSIn this retrospective cohort study, ß-blocker medication does not seem to be associated with a decreased risk of CCM-related hemorrhage at presentation or during follow-up.