Advances & Insights: Neurosciences
April 6, 2006
What the news means for you
Anand G. Vaishnav, MD
Factor VII may still be a viable treatment for some strokes
Reading the JAMA article summarized to the left, it would be easy to assume that factor VII should not be used to treat stroke victims. The figures cited report a high incidence of systemic clot formation (cardiac, ischemic stroke, deep vein thrombosis and pulmonary embolism) following its administration, suggesting increased risk of secondary stroke and the concurrent damage that often accompanies ischemic strokes.
“There is no specific treatment for intracerebral hemorrhage at this time, and they are fatal 30 - 50 percent of the time.”
Types of strokes
Most strokes are caused by blood clots and are called ischemic strokes. They account for about 80 percent of stroke cases. We are currently getting good results from treating this type with tissue plasminogen activator (tPA) within three hours of ischemic stroke onset.
The other type of stroke, hemorrhagic strokes (intracranial hemorrhage), account for only 20 percent of all strokes. Most hemorrhagic strokes are caused by intracerebral hemorrhage (12-14 percent). Unfortunately, there is no specific treatment for intracerebral hemorrhage at this time, and they are fatal 30 - 50 percent of the time. For individuals who survive a hemorrhagic stroke, only 20 percent can live independently at six months, since most of the group suffers severe neurological or cognitive damage of some kind.
Factor VII promising for hemorrhagic strokes
Thus, we are faced with both a high mortality and high morbidity rate for hemorrhagic stroke victims, with little hope for adequate treatment. Potential use of Factor VII needs to be studied.
Standard treatment, according to the “Guidelines for the Management of Spontaneous Intracerebral Hemorrhage,” is blood pressure management and supportive care, and that has not significantly changed hemorrhage volume expansion. Surgical treatments have not reduced the hemorrhage, except for bleeds in one small part of the brain, the cerebellum. What has worked, at least according to an international study in February 2005, is the administration of Factor VII within a period of four hours from the onset of the bleed. A serious thromboembolic event occurred in 7 percent of Factor VII-treated patients as compared to 2 percent of those given a placebo. However, the majority of those patients recovered and the overall frequency of fatal or severe outcomes did not differ significantly between the two groups.
UK stroke research
We need to find treatments that will more adequately preserve quality of life as well as life itself, and our current research at the UK Stroke Clinic is being designed to meet this need. We are part of a large international research study that is currently enrolling participants who consent as they present themselves at the emergency department. The criteria that regulate inclusion in this study will allow us to be more precise in our assessment of the various treatments.
“For an acute disease which has significant high morbidity and mortality, I believe Factor VII may add to our treatment options.”
The UK study is unique because we are controlling for both patient health background and the dosage of Factor VII used. Because of the size of the study, we can offer three different arms (placebo and two different doses). All three groups will be treated according to the current guidelines for standard practice. In that way, we will be able to adequately treat our patients with minimal risk while, at the same time, refining our knowledge of the potential of Factor VII for our most severe stroke patients.
Prevention is key
Preventing strokes through blood pressure control, exercise and regulated diet is the best approach to maintaining one’s health. However, when hemorrhagic strokes happen, we want to be in a better position to provide effective treatments. For an acute disease that has significant high morbidity and mortality, I believe Factor VII may add to our treatment options and we are excited to participate in a major clinical trial addressing the issue.
Dr. Vaishnav is medical director of the stroke unit at UK Chandler Hospital and an assistant professor of neurology at the UK College of Medicine.
Hemophiliac medication associated with increase in stroke events
Since 1999, Factor VII has been licensed to treat bleeding in patients with hemophilia A or B. Factor VII is one of the central proteins involved in coagulation and is also increasingly being used to treat nonhemophiliac stroke victims within three hours of the initial hemorrhage. This increase is evidenced by the fact that only 349 hospitalized patients were treated with Factor VII in 2000, while 4,520 were treated in 2004.
“The authors noted a close association between Factor VII administration and many of the reported blood clots.”
Research looks at adverse events
In a January 18, 2006, article in JAMA (Journal of the American Medical Association), researchers working for the Food and Drug Administration reported on their investigation of adverse events following the administration of Factor VII to stroke victims. The authors reviewed the FDA’s Adverse Event Reporting System (AERS) data, which consisted of 431 reports between March 25, 1999, and December 31, 2004. The database they studied includes adverse event reports from both approved (used in patients with hemophilia) and unlabeled uses, as well as serious adverse events noted in patients who received Factor VII and were enrolled in clinical trials after licensure. Manufacturers are required to report adverse events to the FDA, but notification from clinicians and others is voluntary for spontaneous reports. Therefore, it is believed the data in the AERS underrepresents the actual number of adverse events.
Of the 431 events discovered where the factor had been administered, 168 reports described 185 thromboembolic, or blood clot, events. Unlabeled uses accounted for 151 of the reports, most with active bleeding (n = 115). The kinds of adverse events reported included:
• Ischemic stroke
• Heart attack
• Arterial blood clots
• Pulmonary (lung) blood clots
• Other blood clots in veins (including deep vein thrombosis)
• Clotted devices
In 72 percent of the 50 reported deaths, the probable cause of death was the blood clot event. In 144 patients with timing information, 52 percent of the adverse events occurred in the first 24 hours after the last dose of factor VII (30 events occurred within two hours). In their review of these data, the authors noted a close association between Factor VII administration and many of the reported blood clots. They suggested that the incidence of these events was much more significant than previously suggested in the literature. They noted, however, that the apparent association between an adverse event and the use of Factor VII could reflect other conditions that affected the result of Factor VII. In other words, a variety of disease states may alter the risks and benefits of Factor VII.
UK HealthCare Services - Kentucky Neuroscience Institute
For more information, or to make an appointment with a UK HealthCare physician, please call UK Health Connection at (800) 333-8874.