Rajbeer Singh Sangha, MD
Cronin CA, Sheth KN, Zhao X, Messé SR, Olson DM, Hernandez AF, et al. Adherence to Third European Cooperative Acute Stroke Study 3- to 4.5-Hour Exclusions and Association With Outcome: Data From Get With The Guidelines-Stroke. Stroke. 2014
The Third European Cooperative Acute Stroke Study (ECASS III) showed a benefit to IV tPA treatment 3-4.5 hours from symptom onset. Under instructions from European regulatory authorities, ECASS III excluded 4 patient groups in addition to the standard exclusions in use for 0-3 hours in the United States: (1) age >80, (2) history of stroke and diabetes, (3) any oral anticoagulant treatment regardless of coagulation test results, and (4) NIHSS>25. The authors of this study analyzed data from the national Get With The Guidelines–Stroke (GWTG) database to determine the degree of adherence to additional exclusion criteria for patients treated >3-4.5 hours from symptom onset in the USA.
The results of the study showed that the patients treated in the later time window were younger (mean age 67.1 vs.69.7) and presented with less severe symptoms (NIHSS median 9 vs. 11). Medical comorbidities were similar, except that patients treated in the later time window had a lower rate of atrial fibrillation and coronary artery disease, and a higher rate of smoking. Both these results were interesting as perhaps it reflects overall patient attitude towards their symptoms. Due to the fact that their symptoms were less severe, or the mechanisms involved did not cause significant disability initially, could it be that these patients were waiting for the symptoms to resolve thus leading them to present at a later time.
Interesting results from the analysis showed Age >80 was generally associated with worse outcomes, but without significant differences between time windows except that age >80 was associated with less risk of being non-ambulatory in the >3-4.5hr window compared with the 0-3hr window. Similarly, the combination of prior stroke and diabetes was associated with less risk of being non-ambulatory in the >3-4.5hr window vs. the 0-3hr window.
From the data, the authors determine that strict adherence to clinical trial exclusion criteria is not supported and and thus we should consider patients above the age of 80, NIHSS>25 and warfarin use with INR ≤1.7 amongst others for the time window of 3-4.5 hrs in the administration of tPA. It is my hope that we take the results of this study and apply it to our day to day practice in the hopes that we have positive outcomes that can further be reported. As a greater proportion of the population begins to exceed the age of 80, we must continue to push the limits and boundaries of treatment therapy in a safe and controlled manner. Randomized controlled trials should continue to be conducted to confirm and support the results of this analysis.