Although there were lots of evidences from many clinical trials, the selection of r-tPA dosage of intravenous thrombolysis in AIS is still controversial. In order to solve the dispute, many prospective studies4–9, 13 preset drug dose coefficient, included patients according to the dose coefficient group, and compared the efficacy and safety of thrombolytic. But relative to the question of whether the dose of thrombolytic drugs should be standardized or individualized, maybe the real question the physicians are facing is: For individuals receiving thrombolytic therapy, should the given dose be the maximum safe dose that an individual can accept, or using dose titration to maximize the patients’ benefits? Actually many physicians, when they treated AIS patients with thrombolytic therapy, they still follow the “drug efficacy and safety” principal. Therefore our study is retrospective, based on the real clinical treatment activities, when physicians faced the AIS patients, the dosages of r-tPA were decided at the discretion of each physician according to the situation of each patient. Of course, there are both authenticity and contingency: The efficacy priority or the safety priority; sometimes according to the reaction of patients, decided whether to reduce the dosage in the course of medication; or consideration about the maximum ratio of benefit to cost, etc. Thus, the relationship between the dosage of r-tPA and the prognosis of patients in the real AIS emergency aid is important.
In our study, we found that dose-grouping was not the independently influential factor to the outcome of patients. The characteristics of the patients, especially the NIHSS score, admission glucose and SBP still remained the most common independently influential factors to the prognosis, whatever 3m-mRs0-1 or 24h-sICH and 3m-death indicators. Other common influencing factors included the history of Af, DNT, OTT, diabetes history, et al. The dose-grouping had no significant effect on prognosis in our study. So, does it mean that the choice of thrombolytic dose could be personal?
Indeed, many trials have told us that the standard dose of thrombolytic drugs does not necessarily mean better efficacy, sometimes it does, and sometimes it does not. However, in the same clinical trial, there are often significant differences in the comparison efficacy and safety based on drug dose9,10,14, and it is not consistent about the clinical efficacy and safety corresponding to the drug dose among trials. In our study, dose coefficient had no independent and significant effect on outcomes, which required us to further refine the analysis. However, if we directly used a large set of data to analyze the correlation between drug dose coefficient and AIS outcome, we might lose the accurate description of the data. After all, no matter from the guidance opinions or the clinical practice experience of physicians, the existence of such factors as old age (> 80 years old) or severe stroke itself would question whether thrombolysis should be needed (when DNT > 3h), let alone the choice of drug dosage. This suggested that for AIS patients who are older than 80 years or younger, and whose NIHSS score is greater than or less than a certain critical value, we may need to consider differently about the dosage of r-tPA in order to reduce the risk of 24h-sICH or 3m-death .
The four subgroups in our study represented patients with four different characteristics. In NIHSS score ≥ 16 (severe patients) subgroup, MIOIF was DNT, which were correlated to 3m-mRS 0–1 and 3m-death. While in subgroup of NIHSS score < 16, NIHSS was the MIOIF, which were correlated to 3m-mRS 0–1, 24h-sICH and 3m-death. Multivariate logistic regression analyses showed the drug dose coefficient was negatively correlated with 3m-death. Combined with the analysis of these two subgroups, we found that in AIS patients with relatively mild neurological deficit, the higher dose coefficient would reduce three-month mortality. While, when the nerve function was seriously damaged to a certain extent, the primary factor determining outcome is DNT. In other word, we should give standard dose of r-tPA to the mild disability AIS patients. But in severe AIS patients, we need to minimize the DNT, and give r-tPA to patients as soon as possible.
We used to consider that patients over 80 years might have higher risk of bleeding after thrombolysis, and low dose might reduce such risk1,11. In age ≥ 80 subgroup, we were surprised to find that the main factor affecting the outcome of thrombolysis is not DNT or dose, but diabetes history and NIHSS score on set. The results of this subgroup analysis seemed to highlight the risk of thrombolytic therapy for elderly AIS patients with diabetes, both with the severity at the stroke onset. However, such risk factor does not seem to be highlighted in thrombolytic guidelines1,11, this may be related to the relatively small sample size (51 cases) in our study. In the future, based on the increasing number of patients, more analysis should be needed. In the subgroup of age < 80 years, the main factors influencing the outcome of thrombolytic therapy were DNT, age, NIHSS score and so on "Mainstream factors". It should be noticed that the dose coefficient tended to affect the three-month mortality, which was also negative correlation in criticality. We also look forward to enlarge the sample size to further clarify whether dose coefficient is related to outcomes in r-tPA treated AIS patient or not.