CCE accounts for 14–30% of all cases of ischemic stroke, and has a conversion rate of hemorrhage translation higher than other stroke subtypes[9, 10]. Recombinant tissue plasminogen activator (rtPA) treatment and age are both factors that increase the risk of cerebral parenchymal hemorrhage. Symptomatic intracranial hemorrhage after thrombolytic therapy ranges from 5.9–19.18%[12–14]. In our study, 78 cases were treated by intravenous thrombolysis with rtPA, and 13 patients (16.7%) experienced intracranial hemorrhagic transformation during hospitalization, of which 2 patients (2.56%) had symptomatic intracranial hemorrhage and one died suddenly. The incidence of symptomatic intracranial hemorrhage in our study is lower than that reported in the literature[15–16], a difference which may be because of the modest sample size of our cohort. It has been proposed that the underlying mechanism of this serious complication involves an embolus blocking intracranial vessels, which leads to a local vasospasm. As a result, the fragmented embolus moves distally and recanalizes occluded vessels, whereas damaged and newly formed small vessels rupture causing hemorrhage either from reperfusion injury or because of the activity of associated drugs[8,17−18]. Although we had four cases who experienced extracranial bleeding in our rtPA group, they were not serious bleeding events, both of which improved after symptomatic treatment.
The mortality and disability rate of patients with acute cardiogenic stroke can be as high as 50%. Currently, it is recommended that rtPA thrombolysis occurs within 4.5 h after stroke onset[5, 6]; however, anticoagulation therapy in the early acute stage remains a subject of considerable concern and uncertainty. Two studies, the European Atrial Fibrillation Trial (EAFT) and Studio Italiano Fibrillation Atriale (SIFA), confirmed the safety of warfarin administration during the acute phase of CCE. Further, four randomized control trails[22–25] showed that the bleeding risk of new non-vitamin K antagonist oral anticoagulants is lower than warfarin, and that these drugs work quickly, exhibiting an anticoagulant effect either superior or comparable to warfarin. To date, there have been few small sample size exploratory and observation studies on the use of novel anticoagulants in patients with mild-to-medium acute ischemic stroke related to NVAF[26–29]. In our center, we found that acute phase anticoagulant treatment was more common. In this retrospective study, the NIH scores assigned to the anticoagulant group were between 3 and 13, with an average score of 9. Further, we chose oral warfarin or intravenous argatroban or oral dabigatran within 4.5h, which is earlier than current guideline recommendations. We were most concerned about the risk of bleeding, but the data showed that four patients in the anticoagulant group have intracranial hemorrhagic transformation (4.5%) and that there were no extracranial bleeding events. It is emphasized that anticoagulant therapy was initiated within 4.5 h in our retrospective study, which was earlier than the EHRS “1–3–6–12 d” rule and the ASA/AHA “4–14 d” recommendation, and that intravenous argatroban (direct thrombin inhibitor) was the most common treatment approach, followed by dabigatran anticoagulants and non-controversial heparins, low molecular weight heparin and heparinoids, which also differ compared with that found in other studies. Therefore, we propose that the better prognosis at 3 months in the anticoagulant group was related to time of anticoagulant administration and type of anticoagulant.
In our study, we found that 38.5% of patients from the thrombolytic group, 60.2% of patients from the anticoagulant group, and 47.9% of patients from the antiplatelet group exhibited good prognosis (mRS ≤ 2) at 3 months (P = 0.018), the thrombolytic group did not show a better outcome at 3 months than the other two groups.In addition, we found age differences between groups, in which patients from the thrombolytic group were younger than those from the antiplatelet group, the thrombolytic group had a greater advantage in age; however, we found no difference in 3-month prognosis between groups. Patients from the thrombolytic group did not show greater improvements in disability at 3 months, it must be acknowledged that the thrombolysis group had the highest NIHSS scores on admission ,although there was no statistical differences in NIHSS scores one week after treatment. At the same time,the risk of bleeding was also highest in the thrombolytic group,these all may contribute to the poor prognosis of patients with CCE.
In addition, we also found differences in biochemical indicators among the three groups. Plasma D-dimer levels were measured at admission, and we found the highest levels in patients from the thrombolytic group (P = 0.002), which may also negatively affect prognosis.
Our study has a number of limitations. It is a single center, retrospective study, with a modest sample size and baseline differences between patient subgroups,but it is a study of real world about CCE. Future multicenter, prospective, randomized controlled trails with large patient cohorts are warranted.