Author Interviews, NEJM, Stroke / 10.05.2016
Lower Dose of tPA Found Safer For Patients With Acute Ischemic Stroke
MedicalResearch.com Interview with:
Professor Craig Anderson
Professor of Stroke Medicine and Clinical Neuroscience
Sydney Medical School at the University of Sydney
Institute of Neurosciences of Royal Prince Alfred Hospital
MedicalResearch.com: What is the background for this study?
Prof. Anderson: Intravenous use of the clot-busting drug, alteplase (or rtPA), at a dose of 0.9 mg/kg body weight is the only proven medical treatment of acute ischemic stroke. However, a major drawback to the treatment is an increased risk of major bleeding in the brain, or intracerebral hemorrhage (ICH), that occurs in about 5% of cases, and can be fatal. This balance of effectiveness (recovery from disability) and risks (ICH, and bleeding elsewhere and uncommon drug allergic reactions) has led to much of the controversy over the net benefit of the drug. The optimal dose of the drug has never been established, but the Japanese drug safety regulatory authority, has approved a lower dose (0.6mg/kg) on the basis of a small, non-randomized, open study which showed comparable outcomes and lower risk of ICH than historical controls. This ‘east-west’ divide over the approved dose of alteplase has led to much variation in the dose of alteplase used in clinical practice in Asia – according to a doctor’s perceived risk of ICH in individual patients and the affordability of this relatively expensive treatment in low resource settings. Data from the Get-with-the Guidelines Quality Registry in the United States suggests Asian patients are at higher risk of ICH after standard-dose alteplase than non-Asians.
Our research aimed to resolve this uncertainty over the optimal dose of alteplase, as an international, active-comparator, open-label, blinded outcome assessed, clinical trial of low-dose (0.6 mg/kg) versus standard-dose (0.9mg/kg) in 3310 patients recruited from over 100 hospitals in 13 countries between 2012 and 2015.
(more…)