Low-molecular-weight heparin and early neurologic deterioration in acute stroke caused by large artery occlusive disease.
BACKGROUND
Patients with acute ischemic stroke and large artery occlusive disease (LAOD) have an increased risk for early neurologic deterioration (END) due to progressive stroke, early recurrent ischemic stroke(ERIS), or symptomatic intracranial cerebral hemorrhage(SICH). Low-molecular-weight heparin (LMWH)has been widely advocated to prevent venous thromboembolism,but its risks and benefits in early ischemic stroke are inadequately defined.


OBJECTIVE
To determine the efficacy and safety of LMWH in treating END in patients with acute ischemic stroke and LAOD.


METHODS
Post hoc analysis of randomized, controlled trial.


METHODS
Academic research.


METHODS
Among 603 patients recruited, 353 patients(180 treated with LMWH, 173 with aspirin) had acute ischemic stroke and LAOD.


METHODS
Patients were randomly assigned to receive either subcutaneous LMWH or oral aspirin within 48 hours after stroke onset for 10 days, then all received aspirin once daily for 6 months.


METHODS
We assessed whether LMWH was superior to aspirin for the prevention of END within the first 10 days after index stroke. Early neurologic deterioration was defined as a composite end point of progressive stroke, ERIS, and SICH.


RESULTS
Among 353 patients included in the study, END within the first 10 days occurred in 6.7% of LMWH allocated patients (12 of 180 patients) compared with 13.9% of aspirin-allocated patients (24 of 173). Low molecular-weight heparin was significantly associated with the reduction of END(absolute risk reduction, 7.2%; odds ratio [OR], 0.44; 95% CI, 0.21-0.92). When individual components of END were examined, LMWH was significantly associated with a lower frequency of stroke progression within the first 10 days compared with aspirin(5.0% [9 of 180] vs 12.7% [22 of 173]; OR, 0.36; 95%CI, 0.16-0.81). Meanwhile, among those taking LMWH vs aspirin, the frequency rates of ERIS were 1.1% (2 of 180) vs 0 (0); 0.6% (1 of 180) vs 1.2% (2 of 173) for SICH;and 2.2% (4 of 180) vs 2.9% (5 of 173) for symptomatic and asymptomatic cerebral hemorrhage, respectively; they showed nonsignificant trends. Early neurologic deterioration was significantly associated with 6-month disability with both LMWH(OR, 12.75; 95% CI, 3.27-49.79 on Barthel Index and OR, 18.15; 95% CI, 2.09-157.93 on modified Rankin Scale) and aspirin (OR, 6.09; 95% CI,2.44-15.20 on Barthel Index and OR, 7.50; 95% CI, 2.08-27.04 on modified Rankin Scale) groups.


CONCLUSIONS
For patients with acute ischemic stroke and LAOD, treatment with LMWH within 48 hours of stroke may reduce END during the first 10 days, mainly by preventing stroke progression. The similar rate of cerebral hemorrhage between LMWH and aspirin demonstrated that LMWH may be safely used in acute ischemic stroke.


BACKGROUND
stroke center.org/trials Identifier: FISS -tris
Department of Neurology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai.
Qiaoshu
Q
Wang
Christopher
C
Chen
Xiang Yan
XY
Chen
Jing Hao
JH
Han
Yannie
Y
Soo
Thomas W
TW
Leung
Vincent
V
Mok
Ka Sing Lawrence
KS
Wong
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001157:Arterial Occlusive Diseases / Q000150:complications; D001241:Aspirin / Q000008:administration & dosage; D016009:Chi-Square Distribution; D004333:Drug Administration Routes; D005260:Female; D005500:Follow-Up Studies; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology*; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications* / Q000209:etiology; D013997:Time Factors; D016896:Treatment Outcome
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D001241:Aspirin