Treatment of Acute Ischemic Stroke

I n 1994, a special writing group of the Stroke Council of the AHA published guidelines for the management of patients with acute ischemic stroke. 1 The guidelines, based on the best available evidence, focused primarily on the prevention and treatment of the complications of acute stroke such as cerebral edema and increased intracranial pressure, aspiration pneumonia, urinary tract infections, deep vein thrombosis and pulmonary embolism, decubiti, and seizures.The authors further concluded that "until more data are available, the use of heparin remains a matter of preference for the treating physician" and "that thrombolytic therapy is not currently recommended for the treatment of patients with acute ischemic stroke." 1 No supportive recommendations were given for any neuroprotective strategy, nor therapies given to stimulate neurological recovery.In the 8 years since these guidelines were published, a large number of randomized studies of treatment strategies for acute stroke have been completed.These trials have included thrombolytic agents given intravenously, intra-arterially, or both, antithrombotic and antiplatelet therapies, neuroprotective agents, pharmacological and mechanical therapies to stimulate neurological recovery, and the use of stroke units.In addition, many pilot studies of new therapies for acute stroke have been reported and are entering Phase II and Phase III studies.The current state of knowledge regarding the treatment of acute ischemic stroke that are based on these randomized studies can be summarized as follows.(1) Intravenous thrombolytic therapy, if administered within the first 3 hours after stroke, improves functional outcome after acute ischemic stroke.Even within the first 3 hours, the likelihood of an excellent outcome increases with earlier treatment.The effectiveness of thrombolytic therapy after 3 hours has yet to be conclusively demonstrated but studies are ongoing.(2) Intravascular intervention with medical therapies and mechanical devices is an active area of investigation.(3) Aspirin and other antiplatelet agents are the primary treatment for prevention of recurrent ischemic stroke in the acute care setting.Except for prevention of deep venous thrombosis, heparin and low-molecular weight heparin compounds have limited proven benefit in acute stroke.(4) Care units or multidisci-plinary programs specifically designated for the care of acute stroke patients are associated with improved patient outcomes.(5) Effective neuroprotection for acute ischemic stroke remains a Holy Grail that has yet to be attained.However, several therapies, medical as well as surgical, are currently under study.This article, as well as the companion article in a subsequent issue of Circulation, reviews the basis for these conclusions and the current recommendations for treatment of acute ischemic stroke.In the present article, we will review the use of thrombolytic agents and other recanalization strategies.In the subsequent article, we will discuss neuroprotective strategies such as hypothermia, the use of stroke units, general management of the acute stroke patient, and antithrombotic therapy.