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

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.