Reduction of ischemic sequelae following spontaneous subarachnoid hemorrhage: a double-blind, randomized comparison of enoxaparin versus placebo

Background: Cerebral vasospasm, including its ischemic sequelae, remains a leading cause of death and disability following subarachnoid hemorrhage (SAH). This study was designed to evaluate whether the low-molecular-weight heparin (LMWH) enoxaparin reduces the occurrence of cerebral vasospasm and ischemia following spontaneous SAH. Methods: A prospective, double-blind, randomized study was conducted in 120 consecutive patients with SAH (Hunt Hess Scale (HHS) I–III). Patients received one subcutaneous injection per day of either 20 mg enoxaparin or placebo for 3 weeks following SAH. Efficacy endpoints were the occurrence of cerebral vasospasm, delayed ischemic deficit (DID), cerebral infarction, and overall outcome at 1 year following SAH. Results: At 1-year follow-up, enoxaparin significantly reduced DID and cerebral infarction. Delayed ischemic deficit occurred in 8.8% of the enoxaparin group versus 66.7% of the placebo group (P<0.001), while 3.5% of vasospasm-related cerebral infarctions occurred in enoxaparin-treated patients and 28.3% in placebo-treated patients (P<0.001). Severe shunt-dependent hydrocephalus was significantly lower in the enoxaparin group (1.8% versus 16.7%; P=0.019). Compared with the placebo group, the enoxaparin group had fewer intracranial bleeding events and better overall outcomes at 1-year follow-up. Although there was potential bias as a result of patients in the placebo group being more severely affected (in terms of HHS), treatment with enoxaparin for 3 weeks improved long-term outcome following SAH. Conclusions: Enoxaparin is safe and effective in reducing cerebral vasospasm and ischemia following SAH (Hunt Hess grades I−III), resulting in a better long-term outcome for the patient.