Intravenous tissue-type plasminogen activator for treatment of acute stroke - The standard treatment with alteplase to reverse stroke (STARS) study

Context Tissue-type plasminogen activator (tPA) is the only therapy for acu te ischemic stroke approved by the Food and Drug Administration. Objective To assess the safety profile and to document clinical outcomes an d adverse events in patients treated with intravenous tPA for acute stroke in clinical practice. Design and Setting Prospective, multicenter study of consecutive patients e nrolled between February 1997 and December 1998 at 57 medical centers in th e United States (24 academic and 33 community). Intervention Intravenous tPA (recombinant alteplase). Patients Three hundred eighty-nine patients with a mean age of 69 years (ra nge, 28-100 years); 55% were men. Main Outcome Measures Time intervals between stroke symptom onset, hospital arrival, and treatment with tPA; pretreatment computed tomographic scan re sults, intracerebral hemorrhage, and major systemic bleeding. The modified Rankin Scale score was used to assess clinical outcomes at 30 days. Results Median time from stroke onset to treatment was 2 hours 44 minutes, and the median baseline National Institutes of Health Stroke Scale score wa s 13. The 30-day mortality rate was 13%. At 30 days after treatment, 35% of patients had very favorable outcomes (modified Rankin score, 0-1) and 43% were functionally independent (modified Ran kin score, 0-2). Thirteen patie nts (3.3%) experienced symptomatic intracerebral hemorrhage, including 7 wh o died. Twenty-eight patients (8.2%) had asymptomatic intracerebral hemorrh age within 3 days of treatment with tPA. Protocol violations were reported for 127 patients (32.6%), and included treatment with tPA more than 3 hours after symptom onset in 13.4%, treatment with anticoagulants within 24 hour s of tPA administration in 9.3%, and tPA administration despite systolic bl ood pressure exceeding 185 mm Hg in 6.7%. A multivariate analysis found pre dictors of favorable outcome to be a less severe baseline National Institut es of Health Stroke Scale score, absence of specific abnormalities (effacem ent or hypodensity of >33% of the middle cerebral artery territory or a hyp erdense middle cerebral artery) on the baseline computed tomographic scan, an age of 85 years or younger, and a lower mean arterial pressure at baseli ne. Conclusions This study, conducted at multiple institutions throughout the U nited States, suggests that favorable clinical outcomes and low rates of sy mptomatic intracerebral hemorrhage can be achieved using tPA for stroke tre atment.