Another Effective Treatment for Acute Ischemic Stroke
Abstracts & Commentary
Sources: Sherman DG, et al. Intravenous ancrod for treatment of acute ischemic stroke: The STAT study: A randomized controlled trial. JAMA 2000;283:2395-2403; Mayberg MR, Furlan A. Ancrod—Is snake venom an antidote for stroke? JAMA 2000;283:2440-2442.
Sherman and colleagues tested the efficacy of ancrod in reducing functional disability after acute ischemic stroke. Ancrod, a protease derived from Malaysian pit viper venom, induces rapid defibrinogenation. Defibrinogenation produces anticoagulation, decreased blood viscosity, and stimulates endogenous thrombolysis.
A three-day infusion of ancrod or placebo was administered to 500 patients within three hours after the onset of stroke and was followed by subsequent one-hour infusions at four and five days. A favorable outcome was defined as survival to 90 days with a Barthel Index greater than 95.
Ancrod produced a 7.8% absolute and 22.7% relative improvement in functional status (42.2% in the ancrod group vs 34.4% in the placebo group; P = 0.04). The benefit observed with ancrod was consistent in all patient subgroups defined by age, stroke severity, sex, prestroke disability, and time to treatment. There was a trend toward more symptomatic intracranial hemorrhages in the ancrod group vs. the placebo group (5.2% vs 2.0%; P = 0.06) as well as a significant increase in asymptomatic intracranial hemorrhages (19.0% vs 10.7%; P = 0.01). Mortality at 90 days was not different between the treatment groups.
Although the 8% absolute benefit in full neurological recovery with ancrod is less than the 12% benefit reported in the NINDS intravenous tissue plasminogen activator (tPA) trial (National Institute of Neurological Disorders and Stroke rt-PA Stroke Group Study Group. N Engl J Med 1995;333:1581-1587), the importance of the STAT results is that they confirm the validity of the concept that successful treatment of acute ischemic stroke is possible. Along with the NINDS trial (National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995;333:1581-1587) and the PROAC II study of intra-arterial prourokinase (Furlan A, et al. JAMA 1999;282:2003-2011), STAT reinforces the role of early reperfusion strategies in acute stroke therapy. A further clinical implication of STAT is that ancrod provides another means, in addition to thrombolytic drugs, for improving outcome after acute stroke. As pointed out by Mayberg and Furlan in their editorial, the challenge for clinical research now becomes how to safely combine thrombolytics, microcirculatory reperfusion, antiplatelet, antithrombolic, and, eventually, cytoprotective agents to optimize neurologic outcome. The future of acute treatment for stroke looks both challenging and exciting. —jjc