Response to Letter Regarding Article, “Standard-Dose Intravenous Tissue-Type Plasminogen Activator for Stroke Is Better Than Low Doses”
We thank Doctor Chao et al for their advices on our recent study that whether lower-dose intravenous tissue-type plasminogen activator (tPA) for stroke is as effective and safe as the standard dose.1
When we want to compare the outcomes of ≥2 treatment groups for nonrandomized study, we must adjust the difference of baseline variables. Usually, there are 2 methods for choosing baseline variables included in the multivariable model for calculating adjusted odds ratio. First, we can just choose all significant baseline variables in the univariable analysis. Second, we can choose all possible variables that may affect outcomes according to our clinical experience or the result of other studies. Which of the 2 methods is good is still a matter of debate. But the number of variables you can choose for the multivariable model is related to the sample size of your study. In our study, we used the first method. And in our study, 2-tailed P value of <0.05 was considered to be statistically significant. So age was not a significant baseline variable in the univariable analysis and was not included for adjustment during the analysis. And in our study, even age was included for adjustment during the analysis, and the only effect is that there may be no significant difference in the rate of symptomatic intracranial hemorrhage between 0.7 to 0.85 group and 0.85 to 0.95 group. The study still suggests that standard-dose intravenous tPA for stroke had more favorable outcome without increasing the risk of symptomatic intracranial hemorrhage than low-dose tPA. About other questions, for example, the imbalance of sample size and patient selection in different dosage groups, we had also talked about in the limitations of our study.1
There has never been any randomized clinical trial to test different doses of tPA in acute ischemic stroke. Therefore, there is controversy on the optimal dose of tPA. In theory, the lower dose may lower bleeding risk and also lower the chance of revascularization. So what we want to do is to find a best balance point of dose.
From earlier studies, we find that tPA is also safe for Asians, whether used in a standard or in low dose. Compared with western population, symptomatic intracranial hemorrhage was not increased significantly. And, using the standard-dose tPA showed a nonsignificant trend toward better functional outcomes.2,3 We also read with great interest the article of Chao et al.4 From Table II in the online-only Data Supplement, “Comparisons of treatment results between patients receiving dose of 0.9 mg/kg and those receiving lower doses of rt-PA”, except for 0.6 mg/kg group, the study also showed similar trend in 0.7 to 0.9 mg/kg groups. For 0.6 mg/kg group, the result seems to be difficult to understand because it had both higher symptomatic intracranial hemorrhage rate and higher good clinical outcome.
We also agree that age is the one of most important prognostic factors for patients receiving tPA treatment. For older people, with increase in tPA dose, the bleeding risk may increase more obviously than the benefit of recanalization. But for the study by Chao et al, I think if the difference of the baseline variables could be adjusted when comparing the outcomes of different dosage groups of 71- to 80-years-old patients, the result should be more convincing.
Xiaoling Liao, MD
Yilong Wang, MD
Yongjun Wang, MD
Department of Neurology, Beijing Tiantan Hospital
Capital Medical University
China National Clinical Research Center
for Neurological Diseases
Center of Stroke, Beijing Institute for Brain Disorders
Beijing Key Laboratory of Translational Medicine
for Cerebrovascular Disease
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- © 2014 American Heart Association, Inc.
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