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 20mg 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.
Wurm
Gabriele
G
Department of Neurosurgery, Landesnervenklinik Wagner Jauregg, Wagner-Jauregg-Weg 15, A-4020 Linz, Austria. gabriele.wurm@gespag.at
Tomancok
Berndt
B
Nussbaumer
Karin
K
Adelwöhrer
Cornelia
C
Holl
Kurt
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D002545:Brain Ischemia / Q000188:drug therapy*; D002544:Cerebral Infarction / Q000517:prevention & control; D004311:Double-Blind Method; D017984:Enoxaparin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000188:drug therapy*
D000925:Anticoagulants; D017984:Enoxaparin