Iodinated Contrast Agents Reduce the Efficacy of Intravenous Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke Patients: A Multicenter Cohort Study

Background and Purpose: This study aimed to investigate whether the application of iodinated contrast agents before intravenous (IV) recombinant tissue plasminogen activator (rt-PA) reduces the efficacy in acute ischemic stroke (AIS) patients.  Methods: We analyzed our prospectively collected data of consecutive AIS patients receiving IV rt-PA treatment in the MISSION study. Clinical outcome at 3 months was assessed with modified Rankin Scale (mRS) score and dichotomized into good outcome (0-2) and poor outcome (3-6). Symptomatic intracerebral hemorrhage (sICH) was defined as cerebral hemorrhagic transformation in combination with clinical deterioration of National Institutes of Health Stroke Scale (NIHSS) score ≥4 points at 24-hour. We performed logistic regression analysis and propensity score matching analysis to investigate the impact of iodinated contrast agents before IV rt-PA on poor outcome and sICH, respectively.  Results: A total of 3593 patients were finally included and iodinated contrast agents were used before IV rt-PA among 859 (23.9%) patients. Patients in the iodinated contrast group were more likely to result in poor outcome (39.9% vs 33.4%, P=0.001) and sICH (3.4% vs 1.5%, P<0.001), compared with non-contrast group. Binary logistic regression analysis revealed that the application of iodinated contrast agents was independently associated with poor outcome (OR 1.342; 95% CI 1.103-1.631; P=0.003) and sICH (OR 1.929; 95% CI 1.153-3.230; P=0.012), respectively. After propensity score matching, the application of iodinated contrast agents was still independently associated with poor outcome (OR 1.246; 95% CI 1.016-1.531; P=0.034) and sICH (OR 1.965; 95% CI 1.118-3.456; P=0.019).  Interpretation: Applying iodinated contrast agents before IV rt-PA may reduce the thrombolytic efficacy in AIS patients. Further benefit-risk analysis might be needed when iodinated contrast-used imaging is considered before intravenous thrombolysis.  Clinical Trials: MISSION CHINA study, ClinicalTrials.gov ID: NCT03317639, https://register.clinicaltrials.gov Funding Statement: This work was supported by National Key Research and Development Program of China (2016YFC1300504), National Natural Science Foundation of China (81622017, 81601017), Science Technology Department of Zhejiang Province (2018C04011). Declaration of Interests: All authors declare no conflict of interests. Ethics Approval Statement: The protocol was approved by human ethics committee of The Second Affiliated Hospital of Zhejiang University. The clinical investigation was conducted according to the principles expressed in the Declaration of Helsinki. Written informed consent was obtained from all of the patients.