Low-molecular-weight heparin compared with aspirin for the treatment of acute ischaemic stroke in Asian patients with large artery occlusive disease: a randomised study.
BACKGROUND
Acute stroke patients with large artery occlusive disease (LAOD) have a distinct pathophysiology and may respond differently to anticoagulation treatments. We compared the efficacy of a low-molecular-weight heparin (LMWH), nadroparin calcium, with aspirin in Asian acute stroke patients with LAOD.


METHODS
Acute ischaemic stroke patients with onset of symptoms less than 48 h and LAOD (diagnosed by transcranial doppler imaging, carotid duplex scan, or magnetic resonance angiography) were recruited. Patients were randomly assigned to receive either subcutaneous nadroparin calcium 3800 anti-factor Xa IU/0.4 mL twice daily or oral aspirin 160 mg daily for 10 days, and then all received aspirin 80-300 mg once daily for 6 months. This study is registered at www.strokecenter.org/trials (number 493).


RESULTS
Among 603 patients recruited, 353 (180 LMWH, 173 aspirin) had LAOD (300 had intracranial LAOD only, 42 had both intracranial and extracranial disease, and 11 had extracranial disease only). The proportion of patients with good outcomes at 6 months (Barthel index >or=85) was 73% in the LMWH group and 69% in the aspirin group (absolute risk reduction 4%; 95% CI -5 to 13). Analysis of prespecified secondary outcome measures showed a benefit in outcome for LMWH versus aspirin on the modified Rankin scale dichotomised at 0-1 (odds ratio 1.55, 95% CI 1.02-2.35). Haemorrhagic transformation of infarct and severe adverse events were similar in both groups. Post-hoc analyses of patients without LAOD, and all treated patients, showed similar proportions with a good outcome in aspirin and LMWH groups (78%vs 79% and 73%vs 75%, respectively).


CONCLUSIONS
Overall, the results do not support a significant benefit of LMWH over aspirin in patients with LAOD. The benefits indicated in most outcome measures warrant further investigation into the use of anticoagulation for acute stroke in patients with large artery atherosclerosis, particularly in intracranial atherosclerosis.
Wong
Ka Sing
KS
Department of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China. ks-wong@cuhk.edu.hk
Chen
Christopher
C
Ng
Ping Wing
PW
Tsoi
Tak Hong
TH
Li
Ho Lun
HL
Fong
Wing Chi
WC
Yeung
Jonas
J
Wong
Chi Keung
CK
Yip
Kin Keung
KK
Gao
Hong
H
Wong
Hwee Bee
HB
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001157:Arterial Occlusive Diseases / Q000150:complications*; D044466:Asian People; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002545:Brain Ischemia / Q000150:complications* / Q000208:ethnology; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D017762:Nadroparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000208:ethnology / Q000209:etiology; D016896:Treatment Outcome
D000925:Anticoagulants; D017762:Nadroparin; D001241:Aspirin