TPA in Stroke: The Community Experience

abstract & commentary

Source: Katzan IL, et al. Use of tissue-type plasminogen activator for acute ischemic stroke: The Cleveland area experience. JAMA 2000;283:1151-1158.

The ninds study, published in 1995, demonstrated a beneficial effect of intravenous (IV) tissue plasminogen activator (TPA) for the treatment of ischemic stroke patients presenting within three hours of symptom onset.1 This led to a dramatic alteration in how ischemic stroke is approached. In order to minimize the risks of TPA (which include a tenfold increased risk of intracerebral hemorrhage [ICH]), several authorities developed guidelines regarding the use of thrombolysis in ischemic stroke. Few data exist regarding the outcomes of patients treated with IV TPA for ischemic stroke outside of the investigational setting. This cooperative study conducted in 29 Cleveland-area hospitals examined patients admitted with a primary diagnosis of ischemic stroke. Primary outcome measures included rate of TPA use, occurrence of symptomatic ICH, proportion of patients receiving TPA not in conjunction with published guidelines, and in-hospital mortality.

Over one year, 3948 patients with acute ischemic stroke were identified. Of these, 70 (1.8%) received IV TPA. Eleven of these patients (15.7%) had a symptomatic ICH. Half of the patients receiving IV TPA displayed deviations from criteria for TPA administration as specified in national guidelines. There was a significantly higher rate of in-hospital mortality among patients receiving TPA compared with patients not receiving TPA (15.7% vs 5.1%). The authors concluded that the Cleveland area experience with IV TPA for ischemic stroke differed from that reported in clinical trials.

Comment by Jacob W. Ufberg, MD

Several studies have shown good outcomes and low symptomatic ICH rates among patients treated with IV TPA for acute ischemic stroke within the three-hour window. These include not only the NINDS trial, but also the STARS trial, which is found in the same issue of JAMA as this study.2 As Katzan et al point out, however, many of these trials involved researchers experienced with the use of TPA in stroke, and several were performed in centers that participated in the NINDS or ATLANTIS trials.

This article is among the first to examine the use of IV TPA for stroke outside of a trial setting. The Cleveland area’s high rate of symptomatic ICH is alarming, as is the threefold risk of in-hospital mortality in TPA-treated patients. Equally concerning is the 50% incidence of guideline violations among these 29 hospitals. The STARS study, also a prospective multicenter trial, showed a 35% rate of guideline violations in TPA-treated patients. This highlights one of the major problems in the use of TPA for acute ischemic stroke: If academic neurologists have such great difficulty adhering to the inclusion and exclusion criteria for the use of TPA, how can the rest of us be expected to use TPA properly?


1. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischaemic stroke. N Engl J Med 1995;333:1581-1587.

2. Albers GW, et al. Intravenous tissue-type plasminogen activator for treatment of acute stroke: The Standard Treatment with Alteplase to Reverse Stroke (STARS) study. JAMA 2000;283:1145-1150.

31. According to currently accepted guidelines, what is the time limit (i.e., time after symptom onset) for treating ischemic stroke with intravenous tPA?

a. One hour

b. Three hours

c. Six hours

d. 12 hours