Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Antithrombotic drugs in acute ischemic stroke: a meta-analysis

ACP J Club. 1993 July-Aug;119:9. doi:10.7326/ACPJC-1993-119-1-009


Source Citation

Sandercock PA, van den Belt AG, Lindley RI, Slattery J.Antithrombotic therapy in acute ischaemic stroke: an overview of the completed randomised trials. J Neurol Neurosurg Psychiatry. 1993 Jan;56:17-25.


Abstract

Objective

To study the effectiveness and safety of antithrombotic drugs in early treatment of acute ischemic stroke using meta-analysis.

Data sources

Randomized controlled trials were identified using MEDLINE, consultation with experts, contact with manufacturers, bibliographies, and search of the Antiplatelet Trialists' Collaboration data base.

Study selection

Studies were selected if they used unfractionated or low-molecular-weight (LMW) heparin, oral anticoagulants, or antiplatelet agents (aspirin, ticlopidine, sulphinpyrazone, suloctidil, dipyridamole, indobufen, or flurbiprofen). Trials that randomly assigned patients more than 7 days after a stroke or trials of patients with transient ischemic attacks were excluded. 15 completed trials were analyzed.

Data extraction

Numbers of patients treated and who died from any cause during treatment or follow-up or who had confirmed deep-vein thrombosis (DVT), pulmonary emboli, hemorrhagic transformation, recurrent stroke, or need for assistance with activities of daily living.

Main results

Treatment duration ranged from 6 to 21 days with follow-up for 1 to 12 months. 11 trials studied anticoagulant drugs in acute ischemic stroke (intravenous heparin, n = 2; subcutaneous heparin, n = 4; LMW heparin, n = 4; oral anticoagulants, n = 1). 1 trial evaluated standard heparin in hemorrhagic stroke; 3 trials studied antiplatelet agents. 1047 patients with ischemic stroke received heparin, 46 patients with hemorrhagic stroke received heparin, and 30 patients who had clinical outcomes measured received antiplatelet agents. Patients with ischemic stroke receiving heparin had an 81% reduction in DVT (P < 0.001) compared with placebo. A nonsignificant 12% increase in hemorrhagic transformation of the cerebral infarct was found. There was a nonsignificant trend toward decreased mortality in patients treated with heparin (94 patients [19%] allocated to control medication died vs. 79 patients [16%] allocated to heparin {95% CI for the 3% difference -1% to 8%}[numbers calculated from data in article]; P > 0.1). No data were available on the disability of patients who survived a stroke. The antiplatelet agent and oral anticoagulant trials were too small to be informative.

Conclusion

Heparin in acute ischemic stroke was associated with decreased deep-vein thrombosis. A reduction in mortality and pulmonary emboli cannot be excluded.

Sources of funding: Medical Research Council, UK; Clinical Trials Service Unit; Lilly Pharmaceuticals; Stroke Association.

For article reprint: Dr. P.A. Sandercock, Neurosciences Trials Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom. FAX 44-031-332-5150.


Commentary

Each year approximately 750 000 Americans have a stroke. Most are ischemic, caused by intrinsic atherothrombotic obstruction or by extrinsic embolic obstruction. In recent years, stroke mortality has declined without a concomitant decline in stroke incidence. Of those who survive, 16% become institutionalized, 31% need assistance with self-care, and 71% have a decrease in vocational function (1). The increasing number of disabling strokes has prompted the search for effective treatment. Two approaches have evolved. The first is targeted at preventing ischemic neuronal death (e.g., calcium-channel blockers and amino acid antagonists). The second is aimed at improving cerebral blood flow by preventing or promoting dissolution of clots. Thrombolytic, antithrombotic, and antiplatelet therapies have improved survival in patients with acute ischemic heart disease. It is hoped that, by analogy, these agents will reduce stroke mortality and morbidity. Despite the lack of convincing data, surveys show that many neurologists use antithrombotic therapy in patients with acute ischemic stroke, although half expressed concern about the lack of proven efficacy and the potential risk (2). Therefore, the overview by Sandercock and colleagues is important and timely. By increasing statistical power, meta-analysis may detect clinically important differences between treated and untreated patients, not apparent from the review of individual trials. This overview showed trends but could not state definitively whether antithrombotic therapy reduces mortality, morbidity, or the risk for clinically important complications such as pulmonary embolism. Additional research on the efficacy of antithrombotic and thrombolytic therapy for acute ischemic stroke is needed to determine the risks and benefits.

Brian P. Schmitt, MD
Northwestern University Chicago, Illinois, USA