IV Tissue Plasminogen Activator for Stroke in the Community
What We Know and Don’t Know 10 Years After FDA Approval
Bateman et al1 use the Nationwide Inpatient Sample (NIS) database for 1999 to 2002 to gain insights into the use of IV tissue plasminogen activator (tPA) for acute stroke across a wide range of community hospitals. It is important to note that this was a 20% random sample from NIS and that the ICD 99.10 thrombolysis code is only 50% sensitive for identifying thrombolysis patients. Also, significant variables including baseline stroke severity, neuroimaging data, stroke etiologies, and hospital transfer patterns, as well as 90 day functional outcomes, are not available, which severely limits the conclusions which can be drawn from the database. Thus, although this is the largest “snapshot” we have for IV tPA use in the United States 5 years after FDA approval, the picture remains blurred.
Even allowing for coding inaccuracies, the rate of IV tPA use was distressingly low (2594/250 005=1%). Clinical trials have repeatedly shown that late arrival to hospital and minor or improving neurological deficit are the main reasons patients do not receive IV tPA. In the community this is compounded by difficulty in accessing neurological expertise and by fear of intracerebral hemorrhage. In this regard the study findings are reassuring because the intracerebral hemorrhage rate was only 4.4%. Although the hemorrhage rate was lower than in the NINDS trial, the true rate is uncertain because of inaccuracies inherent in discharge coding. Nonetheless, the NIS hemorrhage rate does suggest that IV tPA can be safely administered in a community setting, which we have also reported in Cleveland.2
IV tPA does not improve stroke mortality, and patients receiving IV tPA typically have higher baseline stroke severity compared with untreated patients. Thus, the study’s finding that inpatient mortality was higher in IV tPA patients even excluding intracerebral hemorrhage is not surprising. Nor is the lack of association between mortality and number of treated patients because there are many confounding variables (eg, emergency room transfers, baseline stroke severity) unable to be addressed in the study. As well, overall inpatient stroke mortality has not been shown to accurately reflect quality of stroke care or to differ significantly between community and academic hospitals.3
Age has consistently been linked with worse stroke outcomes. The significance of other variables such as race, sex or ethnicity cannot be ascertained from this database because, as mentioned, baseline stroke severity and other key information is not available.
Although NIS is the largest IV tPA database yet reported, it perhaps says more about the inadequacies of existing databases than it does about outcomes after IV tPA. Building on studies like Bateman et al, we should refine stroke outcomes assessment to include risk adjustment based on critical baseline variables such as stroke severity, stroke etiologies, and neuroimaging including reperfusion. Although in-hospital outcomes such as length of stay and mortality are of interest, the more relevant stroke outcomes are postdischarge, especially 90-day functional neurological outcomes (I have often argued that clinical practices need to look more like clinical trials in terms of variables and outcomes). It will also be of interest to track stroke outcomes among JCAHO certified primary stroke centers versus noncertified hospitals and to see how the new stroke treatment DRG affects the use of IV tPA. The emphasis on outcomes in medicine will only increase in the current healthcare environment. The challenge will be to assess stroke outcomes in a more standardized meaningful way that leads to improved patient care.
The opinions in this editorial are not necessarily those of the editors or of the American Heart Association.
See related article, pages 440–446.
Bateman BT, Schumacher HC, Boden-Albala B, Berman MF, Mohr JP, Sacco RL, Pile-Spellman J. Factors associated with in-hospital mortality after administration of thrombolysis in acute ischemic stroke patients: an analysis of the Nationwide Inpatient Sample 1999 to 2002. Stroke. 2006; 37: 440–446.
Katzan IL, Hammer MD, Furlan AJ, Hixson ED, Nadzam DM; Cleveland Clinic Health System Stroke Quality Improvement Team. Quality improvement and tissue-type plasminogen activator for acute ischemic stroke: a Cleveland update. Stroke. 2003; 34: 799–800.
Hinchey JA, Furlan AJ, Frank JI, Kay R, Misch D, Hill C. Is In-hospital Stroke Mortality an Accurate Measure of Quality of Care? Neurology. 1998; 50: 619–625.