Truths about the NINDS study: setting the record straight.

Abstract

Thrombolysis for acute ischemic stroke has been studied for more than adecade, but its efficacy remains controversial. The first study to claim thattissue plasminogen activator (tPA) is effective in the treatment of acuteischemic stroke was a multicenter clinical trial coordinated by the NationalInstitute of Neurological Disorders and Stroke (NINDS) Study Group. The NINDSstudy's conclusions, published in1995,1 were that“treatment with intravenous tPA within 3 hours of the onset of ischemicstroke improved clinical outcome at 3 months... [A]s compared with patientsgiven placebo, patients treated with tPA were at least 30% more likely to haveminimal or no disability at 3months.”1(p1586)The NINDS study was widely perceived to be a well-executed and analyzedrandomized controlled trial, and its results were well received by manymedical professionals and thepublic.​thepublic. Table 1 Percentage of patients (N = 320) in the 91 to 180-minute subgroups witha specific baseline National Institutes of Health Stroke Scale (NIHSS)score* Over the past 5 years, tPA therapy for acute ischemic stroke has enteredthe mainstream of emergency medical practice in the United States. When theAmerican Heart Association revised its advanced cardiac life support (ACLS)guidelines for the 2000 ACLS handbook, Guidelines 2000 for CardiopulmonaryResuscitation and Emergency Cardiovascular Care, it gave tPA a class Irecommendation for the therapy of acute ischemic stroke. The American HeartAssociation gives a drug a class I recommendation if the evidence in supportof its effectiveness is considered homogeneous, consistently positive, androbust. Are the NINDS study's results sufficiently robust to withstandrigorous analysis, and is tPA, therefore, fully deserving of a class Irecommendation for the treatment of acute ischemic stroke?