Gumbinger C ,Reuter B ,Stock C ,Sauer T ,Wiethölter H ,Bruder I ,et al. Time to treatment with recombinant tissue plasminogen activator and outcome of stroke in clinical practice: retrospective analysis of hospital quality assurance data with comparison with results from randomised clinical trials. BMJ 2014;348:g3429
My response is as follows:
The authors of this study have erroneously concluded that their study shows "..the effectiveness and safety of thrombolytic therapy in everyday clinical practice..". Efficacy of therapy cannot be proven by an observational study design, only an association.
In addition, there were significant differences between the tPA treated and non treatment groups. Compared to patients who received tPA, patients in the non treatment group were 9.8% more likely to have had a previous stroke, 8.4% less likely to have a baseline mRS of 0-1 and 17.6% less likely to have received stroke centre care. Although having an average stroke severity of 4 points less on the NIHSS, the non treatment group presented much later (49.8% more likely to have presented more than 6 hours from symptom onset). As spontaneous improvement after stroke is commonly seen, the stroke severity at time of onset is likely to be much less, if it existed at all, between the two groups. Despite having an 8.4% lower mRS of 0-1 at baseline compared to those receiving tPA, the non tPA treated group were 8.7% more likely to have an mRS 0-1 at 10 days and 4% less likely to die than those treated with tPA. Whilst the authors report results adjusted for these differences in baseline characteristics, the methods used for these adjustments are not reported. In any case, it is hard to believe that any adjustment could account for such a striking difference in outcomes between the 2 groups.
Given the 4% higher mortality rate in the tPA treated group and the authors acknowledgement that "Thrombolytic therapy beyond the 4.5 hour time window seems to be associated with a significant increase in mortality in clinical practice", it is extremely concerning that the authors advocate that "..patients with a prolonged time from onset to treatment should be included in actual or future randomised controlled trials."
In short, these conclusions stated by the authors in relation to this study are not supported by the data presented.