Medication intake and hemorrhage risk in patients with familial cerebral cavernous malformations

J Neurosurg 137:1088–1094, 2022

The objective of this study was to analyze the impact of medication intake on hemorrhage risk in patients with familial cerebral cavernous malformation (FCCM).

METHODS The authors’ institutional database was screened for patients with FCCM who had been admitted to their department between 2003 and 2020. Patients with a complete magnetic resonance imaging (MRI) data set, evidence of multiple CCMs, clinical baseline characteristics, and follow-up (FU) examination were included in the study. The authors assessed the influence of medication intake on first or recurrent intracerebral hemorrhage (ICH) using univariate and multivariate logistic regression adjusted for age and sex. The longitudinal cumulative 5-year risk of hemorrhage was calculated by applying Kaplan-Meier and Cox regression analyses adjusted for age and sex.

RESULTS Two hundred five patients with FCCMs were included in the study. Multivariate Cox regression analysis revealed ICH as a predictor for recurrent hemorrhage during the 5-year FU. The authors also noted a tendency toward a decreased association with ICH during FU in patients on statin medication (HR 0.22, 95% CI 0.03–1.68, p = 0.143), although the relationship was not statistically significant. No bleeding events were observed in patients on antithrombotic therapy. Kaplan-Meier analysis and log-rank test showed a tendency toward a low risk of ICH during FU in patients on antithrombotic therapy (p = 0.085), as well as those on statin therapy (p = 0.193). The cumulative 5-year risk of bleeding was 22.82% (95% CI 17.33%–29.38%) for the entire cohort, 31.41% (95% CI 23.26%–40.83%) for patients with a history of ICH, 26.54% (95% CI 11.13%–49.7%) for individuals on beta-blocker medication, 6.25% (95% CI 0.33%–32.29%) for patients on statin medication, and 0% (95% CI 0%–30.13%) for patients on antithrombotic medication.

CONCLUSIONS ICH at diagnosis was identified as a risk factor for recurrent hemorrhage. Although the relationships were not statistically significant, statin and antithrombotic medication tended to be associated with decreased bleeding events.

The impact of statin therapy after surgical or endovascular treatment of cerebral aneurysms

J Neurosurg 133:182–189, 2020

Cerebral aneurysms represent the most common cause of spontaneous subarachnoid hemorrhage. Statins are lipid-lowering agents that may expert multiple pleiotropic vascular protective effects. The authors hypothesized that statin therapy after coil embolization or surgical clipping of cerebral aneurysms might improve clinical outcomes.

METHODS This was a retrospective cohort study using the National Health Insurance Service–National Sample Cohort Database in Korea. Patients who underwent coil embolization or surgical clipping for cerebral aneurysm between 2002 and 2013 were included. Based on prescription claims, the authors calculated the proportion of days covered (PDC) by statins during follow-up as a marker of statin therapy. The primary outcome was a composite of the development of stroke, myocardial infarction, and all-cause death. Multivariate time-dependent Cox regression analyses were performed.

RESULTS A total of 1381 patients who underwent coil embolization (n = 542) or surgical clipping (n = 839) of cerebral aneurysms were included in this study. During the mean (± SD) follow-up period of 3.83 ± 3.35 years, 335 (24.3%) patients experienced the primary outcome. Adjustments were performed for sex, age (as a continuous variable), treatment modality, aneurysm rupture status (ruptured or unruptured aneurysm), hypertension, diabetes mellitus, household income level, and prior history of ischemic stroke or intracerebral hemorrhage as time-independent variables and statin therapy during follow-up as a time-dependent variable. Consistent statin therapy (PDC > 80%) was significantly associated with a lower risk of the primary outcome (adjusted hazard ratio 0.34, 95% CI 0.14–0.85).

CONCLUSIONS Consistent statin therapy was significantly associated with better prognosis after coil embolization or surgical clipping of cerebral aneurysms.

 

Effect of statin treatment on vasospasm-related morbidity and functional outcome in patients with aneurysmal subarachnoid hemorrhage

J Neurosurg 127:291–301, 2017

The efficacy of statin therapy in treating aneurysmal subarachnoid hemorrhage (SAH) remains controversial. In this meta-analysis, the authors investigated whether statin treatment significantly reduced the incidence of cerebral vasospasm and delayed neurological deficits, promoting a better outcome after aneurysmal SAH.

METHODS: A literature search of the PubMed, Ovid, and Cochrane Library databases was performed for randomized controlled trials (RCTs) and prospective cohort studies investigating the effect of statin treatment. The end points of cerebral vasospasm, delayed ischemic neurological deficit (DIND), delayed cerebral infarction, mortality, and favorable outcome were statistically analyzed.

RESULTS Six RCTs and 2 prospective cohort studies met the eligibility criteria, and a total of 1461 patients were included. The meta-analysis demonstrated a significant decrease in the incidence of cerebral vasospasm (relative risk [RR] 0.76, 95% confidence interval [CI] 0.61–0.96) in patients treated with statins after aneurysmal SAH. However, no significant benefit was observed for DIND (RR 0.88, 95% CI 0.70–1.12), delayed cerebral infarction (RR 0.66, 95% CI 0.33–1.31), mortality (RR 0.69, 95% CI 0.39–1.24) or favorable outcome, according to assessment by the modified Rankin Scale or Glasgow Outcome Scale (RR 0.99, 95% CI 0.92–1.17).

CONCLUSIONS Treatment with statins significantly decreased the occurrence of vasospasm after aneurysmal SAH. The incidence of DIND, delayed cerebral infarction, and mortality were not affected by statin treatment. Future research should focus on DIND and how statins influence DIND.