REVIEW QUESTION

Is low-molecular-weight heparin (LMWH) or heparinoids more effective than unfractionated heparin in the treatment of patients with acute ischemic stroke?

TYPE OF REVIEW

A systematic review of nine randomized controlled trials.

RELEVANCE FOR NURSING

Despite the widespread use of anticoagulants in patients with acute ischemic stroke, their efficacy and safety remain uncertain. Providers who prescribe anticoagulants must balance their efficacy in reducing the risk of deep vein thrombosis (DVT), pulmonary embolism, and other related conditions with the increased risk of severe bleeding. Furthermore, the danger of anticoagulants causing hemorrhagic transformation (the development of hemorrhage in the ischemic area) is so widely known that many providers are reserving anticoagulants for select cases of progressive or cardioembolic stroke.

Intravenous heparin, the most widely used anticoagulant in the acute care setting, is gradually being replaced by subcutaneous LMWH or heparinoids, which have a more predictable dose-response relationship. LMWH is a new class of anticoagulants that have pharmacokinetic and biological advantages over unfractionated heparin, including more powerful antithrombotic effects and a lower risk of bleeding complications.

CHARACTERISTICS OF THE EVIDENCE

The purpose of this review was to determine which types of anticoagulants are most effective in the prevention of blood clots in patients who have recently had an acute ischemic stroke. The review included nine randomized controlled trials, for a total of 3,137 patients. The trials compared LMWH or heparinoids with unfractionated heparin in people with a recent onset of stroke symptoms.

There was no evidence that, when compared with unfractionated heparin, LMWH or heparinoids was associated with fewer deaths from all causes during the treatment period. Although both LMWH and heparinoids were associated with significantly fewer DVTs than unfractionated heparin, the number of major events such as pulmonary embolism and intracranial hemorrhages was too small to determine whether the harms of LMWH and heparinoids outweighed their benefits. For people with ischemic stroke who need immediate treatment with anticoagulants, these clinical trials did not provide reliable evidence on the risk-benefit for each type of heparin.

BEST PRACTICE RECOMMENDATIONS

Treatment with LMWH or heparinoids after an acute ischemic stroke appears to decrease the occurrence of DVT, compared with standard unfractionated heparin treatment. However, there are too few data to provide reliable information on the effects of these drugs on other important outcomes, including functional outcome, death, and intracranial hemorrhage. It is important to bear in mind that even if no superiority of LMWH over unfractionated heparin should emerge, LMWH nevertheless facilitates patient management because it is easier to administer and dose, though still more difficult than oral medications.

RESEARCH RECOMMENDATIONS

Because aspirin may be the antithrombotic agent with the most favorable risk-benefit profile, large-scale trials should be conducted comparing aspirin alone with aspirin plus low-dose LMWH or heparinoids in people at high risk for DVT and pulmonary embolism. A trial comparing a more aggressive LMWH or heparinoid regimen with unfractionated heparin and with aspirin in certain patients, such as those with a cardiac source of emboli, should also be done.

REFERENCE