TUCSON—Although plenty of proof exists that antithrombotic agents can prevent stroke, their use after acute ischemic stroke is controversial. A joint committee of the American Academy of Neurology (AAN) and the American Stroke Association (ASA) has therefore reviewed the literature to determine how antiplatelet and anticoagulant drugs affect acute ischemic stroke morbidity, mortality, and recurrence.[1]

In addition, the joint committee evaluated the risks and benefits of using antiplatelet and anticoagulant drugs for deep venous thrombosis (DVT) and pulmonary embolism (PE) in stroke patients, and it assessed their influence on cardiovascular complications. Committee members also sought to identify any variation in effectiveness by ischemic stroke subtypes. Their recommendations are summarized here.

METHODOLOGY

The joint committee conducted a thorough literature review, which identified 2,372 relevant papers. After careful examination, the committee found that only 10 papers met its criteria for analysis. Based on this evidence, the committee developed its recommendations for the use of antiplatelet and anticoagulant drugs in acute ischemic stroke. The recommendations received a grade of A (highest), B, or C (lowest), depending on the strength of the evidence to support them.

ANTIPLATELET DRUGS

Most patients with acute ischemic stroke who present within 48 hours of symptom onset should take 160 to 325 mg/d of aspirin to lower stroke morbidity and mortality (Grade A). “Aspirin certainly is not penicillin, but the data suggest that it is beneficial in stroke,” remarked Bruce M. Coull, MD, an AAN/ASA joint committee member and Head of the Department of Neurology at the University of Arizona in Tucson. The recommendation about aspirin applies, he noted, provided there are no contraindications, such as aspirin allergy or gastrointestinal bleeding, and the patient has not already been or will not be treated with recombinant tissue-type plasminogen activator.

The morbidity and mortality reductions with aspirin are small but statistically significant.[2] Due to insufficient data, no recommendations can be made about the use of any other antiplatelet agent in acute ischemic stroke.

ANTICOAGULANTS

• DVT prophylaxis: Subcutaneous unfractionated heparin, low-molecular-weight (LMW) heparins, and heparinoids may be used to prevent DVT in at-risk patients with acute ischemic stroke (Grade A). “This is important because people do die from pulmonary emboli when they are immobilized,” stressed Dr. Coull. He cautioned, however, that too few data exist to determine whether anticoagulants reduce PE incidence.

The benefits of anticoagulant drugs must be weighed against the risk of systemic and intracerebral hemorrhage. Physicians should also keep in mind that pneumatic compression devices and other nonpharmacologic means of DVT prevention exist.

• Fixed-dose subcutaneous unfractionated heparin: This form of heparin administration is not recommended for decreasing acute ischemic stroke–related morbidity or mortality or for preventing an early recurrence (Grade A). There is some evidence that fixed-dose subcutaneous unfractionated heparin reduces the likelihood of an early recurrence of acute ischemic stroke, but a concomitant increase in the frequency of hemorrhage negates that benefit.

• Dose-adjusted unfractionated heparin: If given within the first 48 hours after an acute stroke, this type of administration does not appear to reduce morbidity, mortality, or early recurrence (Grade B). Furthermore, dose-adjusted unfractionated heparin may increase the risk of bleeding complications.

• High-dose LMW heparins and heparinoids: These agents are not recommended for reducing morbidity, mortality, or early recurrence in acute ischemic stroke (Grade A). These agents have been found to be neither beneficial nor harmful in this capacity.

STROKE SUBTYPES

Aspirin, not dalteparin, is recommended for the various acute ischemic stroke subgroups—cardioembolic, large-vessel atherosclerotic, vertebrobasilar, and progressing (Grade A). High-dose dalteparin may be efficacious in patients with atrial fibrillation, but no more so than aspirin. Furthermore, aspirin is easier to administer.

Unfractionated heparin and high-dose LMW heparins or heparinoids are not recommended for any acute ischemic stroke subgroup due to insufficient data. This recommendation received a grade of U, indicating that, because of the lack of data, this issue is unresolved.

FURTHER RESEARCH

Another relevant study was published after the joint committee completed its recommendations, and the findings were consistent with the committee’s conclusions. In this study, medium or high doses of the LMW heparin tinzaparin, administered within 48 hours of acute ischemic stroke, were less effective than aspirin in improving functional outcomes. High-dose tinzaparin did prevent DVT more effectively than did aspirin, but it also produced higher rates of symptomatic intracranial hemorrhage.[3]

The joint committee suggested that additional well-designed, prospective, randomized clinical trials be performed to address several issues in acute ischemic stroke treatment, such as the merits of early versus delayed (after 24 to 48 hours) initiation of anticoagulation and whether other oral antiplatelet agents work as well as aspirin. Future trials could also attempt to determine whether intravenous heparinoids are effective for large vessel atherothrombotic stroke and whether unfractionated heparin is useful in acute ischemic stroke.

—Timothy Begany

References
1. Coull BM, Williams LS, Goldstein LB, et al. Anticoagulants and antiplatelet agents in acute ischemic stroke: report of the Joint Stroke Guideline Development Committee of the American Academy of Neurology and the American Stroke Association (a division of the American Heart Association). Neurology. 2002;59:13-22.
2. Chen ZM, Sandercock P, Pan HC, et al. Indications for early aspirin use in acute ischemic stroke: a combined analysis of 40,000 randomized patients from the Chinese Acute Stroke Trial and the International Stroke Trial. On behalf of the CAST and IST collaborative groups. Stroke. 2000;31:1240-1249.
3. Bath PM, Lindenstrom E, Boysen G, et al. Tinzaparin in Acute Ischemic Stroke (TAIST): a randomized aspirin-controlled trial. Lancet. 2001;358:702-710.

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