Background
Each year, 1 million people are hospitalized with a diagnosis of stroke; it was the fourth-leading cause of death in the U.S. in 2009 and 2010.1 The majority of strokes (80%) are caused by focal cerebral ischemia, and the remainder are caused by hemorrhage.1 In 2008, the direct medical costs of stroke were approximately $18.8 billion, with almost half of this amount directed toward hospitalization.1 Although stroke inpatients make up only 3% of total hospitalizations, the mortality rate is more than twice that of other patients’.1
Over the past several decades, much has been learned about the pathophysiology and treatment for ischemic stroke. The mainstays of therapies include restoring perfusion in a timely manner and targeting both clot formation and hemostasis. These therapies improve patient outcomes and reduce the risk of recurrence in appropriately selected populations.
Guideline Update
In February, the American College of Chest Physicians (ACCP) published new practice guidelines for medical patients regarding antithrombotic and thrombolytic therapy in acute ischemic stroke.2 These evidence-based guidelines are the result of new clinical trial data and a review of previous studies. They address three aspects of management decisions for stroke, including acute treatment, VTE prevention, and secondary prevention, as well as specifically address the treatment of cerebral venous sinus thrombosis.
In the management of acute ischemic stroke, several recommendations were made. In terms of IV recombinant tissue plasminogen activator (r-tPA) administration, the guidelines were expanded and allow for a less restrictive time threshold for administration. Previous recommendations limited the usage of IV r-tPA to within three hours of symptom onset in acute ischemic stroke. A science advisory from the American Heart Association/American Stroke Association (AHA/ASA) from 2009 extended that window to 4.5 hours. The 2012 ACCP guidelines have followed suit to extend this time to 4.5 hours from symptom onset as well.
In addition, intrarterial r-tPA can be given in patients not eligible for IV r-tPA within six hours of presentation of acute ischemic stroke due to proximal cerebral artery occlusion.
These updated acute stroke guidelines recommend against the use of mechanical thrombectomy based mostly on lack of data rather than lack of benefit.2
The new guidelines continue to recommend early aspirin therapy at a dosage of 160 mg to 325 mg within the first 48 hours of acute ischemic stroke. Therapeutic parenteral anticoagulation with heparin or related drugs was not recommended in patients with noncardioembolic stroke due to atrial fibrillation (afib) or in patients with stroke due to large artery stenosis or arterial dissection. In this updated analysis, there was no benefit of anticoagulation compared with antiplatelet therapy, and the risk for extracranial hemorrhage was increased. No specific recommendation regarding anticoagulation was made in patients with mechanical heart valves or intracardiac thrombus.
Updates have been made for VTE prophylaxis in patients hospitalized for acute stroke. In stroke patients with restricted mobility, prophylactic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) and/or intermittent pneumatic compression devices should be initiated as early as possible. The panel is no longer recommending elastic compression stockings as VTE prevention given the risk of skin damage and no clear benefit in symptomatic VTE prevention. For patients with hemorrhagic stroke and restricted mobility, similar recommendations were made for VTE prevention, except to start pharmacologic treatment between days 2 and 4 of the hospital stay. However, if there is a bleeding concern, intermittent pneumatic compression devices are favored over pharmacologic prophylaxis. In all patients for whom pharmacologic prevention is utilized, prophylactic LMWH is preferred over UFH.
Secondary stroke prevention is addressed, with 2012 guidelines outlining a preference for clopidogrel or aspirin/extended-release dipyridamole rather than aspirin or cilostazol in patients with a history of noncardioembolic ischemic stroke or TIA. Oral anticoagulation is preferred in patients with a history of stroke or TIA with afib over aspirin alone, aspirin plus clopidogrel, or no antithrombotic therapy. Of the available anticoagulants, the panel recommended dabigatran 150 mg twice daily over adjusted-dose warfarin.2 This recommendation is based on results from the RE-LY trial, which showed dabigatran as noninferior to warfarin in patients with nonvalvular afib without severe renal failure or advanced liver disease.3