What is the efficacy of early anticoagulation in the treatment of acute ischemic stroke?

Updated: Dec 18, 2018
  • Author: Salvador Cruz-Flores, MD, MPH, FAHA, FCCM, FAAN, FACP, FANA; Chief Editor: Helmi L Lutsep, MD  more...
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Current data do not support the routine use of anticoagulation for acute ischemic stroke. Several randomized, controlled trials that used IV heparinoids, subcutaneous low-molecular-weight heparin (LMWH), or subcutaneous unfractionated heparin (UFH) early after ischemic stroke failed to show a significant overall benefit of treatment over controls.

The International Stroke Study (IST) compared aspirin with subcutaneous UFH at 2 different doses (5000 units or 12,500 units bid); no difference in morbidity and mortality from stroke was shown between the group treated with aspirin and the group treated with UFH. In addition, although UFH seemed to decrease the risk of pulmonary embolism and deep venous thrombosis (DVT), it increased the risk of hemorrhagic complications.

A systematic review by the Cochrane collaboration demonstrated that anticoagulation (with UFH, LMWH, heparinoids, oral anticoagulants, or thrombin inhibitors) did not decrease the odds of death or development of dependency from stroke. [8] Although anticoagulants prevented pulmonary embolism, they also increased the risk of hemorrhage, leading to the conclusion that anticoagulation cannot be recommended for the treatment of acute ischemic stroke.

The last trial evaluating early intravenous anticoagulation with UFH was published in 1986. It showed no benefit in the treatment arm compared with the control arm.

An exception to the lack of benefit from anticoagulation might be in patients with acute ischemic stroke ipsilateral to a severe stenosis or occlusion of the internal carotid artery. In the TOAST (Trial of Org 10172 in Acute Stroke Treatment) trial, this group appeared to benefit from early IV administration of the LMWH danaparoid. However, this was a post hoc analysis with a small number of individuals, so the effect of chance cannot be excluded. Therefore, further research is needed to confirm the findings. [9]

If early anticoagulation after ischemic stroke is indicated but UFH is contraindicated because of large brain infarctions, hemorrhagic infarctions, or pronounced microangiopathic changes in the brain, LMWH (in a body-weight–adapted dose) could be used because of lower bleeding risk, although this recommendation is not based on solid evidence.

In patients with acute ischemic stroke and atrial fibrillation, a controlled, randomized study (Heparin in Acute Embolic Stroke Trial [HAEST]) failed to show the superiority of LMWH (dalteparin 100 IU/kg subcutaneously bid) to aspirin (160 mg/d). [10] On the basis of this evidence, patients with acute ischemic stroke and atrial fibrillation should be treated with aspirin in the acute phase (and then placed on anticoagulation).

When long-term anticoagulation is indicated, the use of UFH or LMWH has been advocated to serve as a bridge while a therapeutic international normalized ratio (INR) is achieved with warfarin. A small pilot study found that LMWH (enoxaparin 1 mg/kg subcutaneously bid) was safer than IV UFH for this purpose in patients with subacute cerebral ischemia. [11] However, further studies are needed to confirm this finding before this approach can be recommended generally.

Despite evidence from the randomized clinical trials discussed above, anticoagulation continues to be recommended for some specific clinical situations. These recommendations are based on uncontrolled studies and expert opinion.

Even among experts there is disagreement about the best level of anticoagulation, route of administration, timing and duration of treatment, use of a bolus dose, and safety of the therapy, given the severity of neurologic deficits, size of infarction on baseline computed tomography (CT), vascular distribution, or presumed cause of stroke.

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