Heparin in the treatment of aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

Abstract

OBJECTIVE Cerebral vasospasm and the resulting infarction remain the most devastating complications of aneurysmal subarachnoid hemorrhage (aSAH). Limited treatment options are available, with nimodipine as the only approved prophylactic medication. In addition to its anticoagulant properties, heparin also has a pleiotropic and anti-inflammatory effect that could be beneficial in vasospasm. In this study, the authors sought to evaluate the efficacy and safety of heparin in the treatment of aSAH. METHODS The PubMed, EBSCOhost, Europe PMC, and Cochrane Central databases were searched to find studies including patients with aSAH who were treated with intravenous unfractionated heparin (UFH) after an aneurysm-securing procedure. Studies that did not include a comparison with UFH or low-molecular-weight heparin in deep vein thrombosis prophylactic doses were excluded. The primary outcome was cerebral vasospasm, and the secondary outcomes were cerebral infarction, clinical deterioration caused by delayed cerebral ischemia, bleeding complications, and thromboembolism complications. RESULTS Overall, 5 nonrandomized studies were included; 4 studies evaluated the safety and 3 studies evaluated the efficacy of intravenous heparin. From the analysis of 3 studies with a total of 895 patients, administration of intravenous UFH for > 48 hours was related to a significantly lower rate of cerebral infarction (OR 0.44, 95% CI 0.25–0.79). No significant association was found with other efficacy outcomes. Regarding cognitive outcome, one study found a significant improvement in Montreal Cognitive Assessment scores; however, the functional outcome as indicated by the modified Rankin Scale score was not improved by heparin administration. From the analysis of 4 studies with 1099 patients, no significant increases in bleeding and other complications were found. CONCLUSIONS Administration of intravenous UFH for more than 48 hours reduced the rate of cerebral infarction with a good safety profile. This result supports the ongoing clinical trial.

Red-cell distribution width as a prognostic marker for aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis

“…Several prophylactic treatments for cerebral infarction are currently under research, including but not limited to nimodipine, clazosentan, and heparin. 4 , 5 , 6 The availability of an accurate prognostic model can provide tremendous help in risk stratification before beginning treatment. The currently established predictors for aSAH patients are the HH scale, WFNS scale, and modified Fisher scale.…”

“…Fortunately, recent years have seen a surge in research trying to find a suitable prophylactic treatment with several drugs showing good potential, such as nimodipine, clazosentan, and heparin. 4 , 5 , 6 With a possible paradigm shift in the treatment strategy of aSAH, an excellent prognostic model is required to identify high-risk patients that would likely benefit from such a preventative treatment strategy.…”

Associations of neutrophil to lymphocyte ratio and red cell distribution width on different days with the prognosis of aneurysmal subarachnoid hemorrhage patients

“…[21] One systematic review and meta-analysis exploring the association of RDW with prognosis in aneurysmal subarachnoid hemorrhage patients confirmed that higher RDW was associated with a worse functional outcome, a worse discharge and 3-month functional outcome, and a higher in-hospital and 90-day mortality. [22] In another study carried in 8175 community-dwelling adults 45 years or older and exploring the association between RDW and risk of death, the results showed that RDW was a widely available test and a strong predictor of mortality in the general population of adults 45 years or older. [23] In our study, the univariate analysis results showed that the levels of RDW on the preoperative day, the 1st, 3rd and 7th postoperative days were all associated with the prognosis of aSAH patients, further suggesting that RDW might be a highly advantageous prognostic indicator.…”

Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An “Heparin Oriented” Systematic Review

“…The Heparin cohort was 1.9 times less likely to develop delayed neurological damage and 2.5 times less likely to develop cerebral infarction as demonstrated by multivariate analysis. Finally, the meta-analysis of Lukito et al confirmed that heparin treatment for at least 48 h is associated with reduced occurrence of brain infarction showing at the same time adequate treatment safety [152]. Wurm et al analyzed 120 consecutive patients with aSAH (Hunt-Hess I-III), after aneurysm repair, randomly allocated to either one subcutaneous injection of 20 mg enoxaparin or placebo for 21 days following SAH.…”