Jennifer Harris, MD
Thrombolytic therapy with intravenous recombinant tissue plasminogen activator (r-tPA) is an effective treatment in acute ischemic stroke. Several studies have examined functional outcome and mortality at 3 months after intravenous r-tPA treatment. However, data on long-term outcome are limited. Two randomized controlled stroke trials, the National Institute of Neurological Disorders and Stroke trial (NINDS) and the third International Stroke Trial (IST-3), have examined long-term mortality after intravenous r-tPA and revealed no differences in mortality rates among treated and nontreated patients at 12- and 18-months follow-up, respectively.
To explore long-term clinical outcome after intravenous r-tPA, Yu et al. conducted a nationwide register-based follow up study using a propensity score matching method. Using the Ontario Stroke Registry, they identified 29,036 patients with ischemic stroke and used propensity score methods to match the 4,449 patients treated with intravenous r-tPA to nontreated patients. The primary outcome was 1-year home-time, which was defined as the number of days spent outside of any healthcare institutions, and showed that compared with nontreated patients, those treated with intravenous r-tPA experienced a mean of 9.5 additional days at home in the first year. Now, while looking at these results from an individual patient perspective, this might seem like a rather small improvement; however, looking at the larger picture, it can mean significant cost savings for the healthcare system at large. With roughly 700,000 ischemic strokes occurring annually in the United States, and associated stroke care costs estimated at $34 billion each year, even a small increase in the rate of thrombolysis could potentially lead to reduced hospital stays and large costs savings.
The study also found that patients treated with intravenous r-tPA were less likely to be admitted to a nursing home in the first year after stroke compared with patients who did not receive this treatment. Importantly, like the NINDS and IST-3 trials, there was no difference in mortality between the groups at one year, implying that treatment with intravenous r-tPA is safe and not associated with increased mortality.
Although overall the results add to the evidence to support the benefits of intravenous r-tPA, the study has several limitations worth mentioning. For example, the reasons for nontreatment with r-tPA were not given, which could potentially lead to residual confounding. Furthermore, not all factors that might affect outcome were matched, including care at a stroke center versus not. Lastly, the authors used home-time as a surrogate for disability rather than using direct measures of functional status or quality of life after hospital discharge. Despite, these limitations, the results suggest a long-term benefit of r-tPA. Further studies regarding long-term outcome are needed, particularly in light of the emergence of extended time window thrombolysis and alternative agents.