Low-Molecular-Weight Heparin Versus Aspirin for Acute Ischemic Stroke With Large Artery Occlusive Disease

Abstract

Background and Purpose— The Fraxiparin in Stroke Study for the treatment of ischemic stroke (FISS-tris) study showed no superiority of low-molecular-weight heparin (LMWH) over aspirin for the primary end point (Barthel Index) in acute ischemic stroke due to large artery occlusive disease. This study aims to evaluate the efficacy of LMWH and aspirin in selected subgroups so as to generate hypotheses for further studies. Methods— The FISS-tris study was a multicenter, randomized trial to investigate the efficacy and safety of LMWH (nadroparin calcium 3800 antifactor Xa IU/0.4 mL subcutaneously twice daily) or aspirin (160 mg once daily) for the treatment of patients with acute ischemic stroke and large artery occlusive disease. The primary outcome was the Barthel Index score dichotomized at 85 6 months poststroke. Exploratory subgroup analysis was performed using different levels of baseline characteristics and the distribution of symptomatic arteries. Results— Compared with aspirin, LMWH improved outcome among older patients >68 years ( P =0.043; OR, 1.86; 95% CI, 1.02–3.41) without ongoing antiplatelet treatment on admission ( P =0.029; OR, 1.85; 95% CI, 1.06–3.21) and with symptomatic posterior circulation arterial disease ( P =0.001; OR, 5.76; 95% CI, 2.00–16.56). Conclusions— Our findings suggest that LMWH may be of benefit in certain subgroups of patients with acute cerebral infarct and large artery occlusive disease. Hence, further investigation of LMWH may be justified in subgroups such as the elderly, nonusers of antiplatelet agents, and patients with posterior circulation stenosis. Clinical Trial Registration— URL: www.strokecenter.org/trials . Unique identifier: registration no. 493.

Low-Molecular-Weight Heparin or Dual Antiplatelet Therapy Is More Effective Than Aspirin Alone in Preventing Early Neurological Deterioration and Improving the 6-Month Outcome in Ischemic Stroke Patients

“… 42 Retrospective studies also suggest that anticoagulation can improve the outcome in certain subgroups of patients with severe stenosis (70-99%) or vertebrobasilar disease. 20 , 21 Thus, the present findings support a potential role of LMWH or DAT as an effective antithrombotic therapy in the elderly.…”

“…In this study, LMWH was superior to aspirin for the prevention of END and ERIS, which is consistent with another study involving Asians. 20 However, the previous FISS-tris trial revealed no significant benefit of LMWH over aspirin in patients with LAOD. 38 However, the FISS-tris trial had a small sample (353 in total, comprising 180 LMWH- and 173 aspirin-treated patients), and it did not examine early effectiveness.…”

“… 19 In addition, it has been suggested that anticoagulation therapy is effective in certain subgroups of patients, such as those with posterior circulation stenosis or vertebrobasilar disease. 20 , 21 However, these observations were not supported by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) or Tinzaparin in Acute Ischemic Stroke Trial (TAIST) results. 22 , 23 , 24 Asians have a higher prevalence than other populations of atherosclerosis development in the intracranial arteries, 25 which might explain why the beneficial effect of LMWH in Chinese patients was not reproduced in studies of Caucasians.…”

Symptomatic Carotid Occlusion Is Frequently Associated With Microembolization

“…37 Given the frequency of microembolization we observed, prior trial results demonstrating MES reduction with dual antiplatelet therapy, and possible clinical benefit of anticoagulation in patients with stroke due to large vessel disease, further investigation of aggressive antithrombotic regimens among patients with symptomatic carotid occlusions may be warranted. 25, 26, 29, 38, 39 …”

Low-Molecular-Weight Heparin in Atherosclerotic Stroke

“…6 They found that LMWH improved outcomes in certain subgroups such as the elderly, antiplatelet nonusers, and patients with posterior circulation stroke. This benefit was not clearly documented in a WASID subgroup analysis, 7 which may be attributed to differential anticoagulation administration timing.…”