This analytical descriptive study, searched the rt-PA complications in treatment of ischemic stroke patients who were admited in Vali-e-Asr hospital in Birjand between 2016–2017. Results of this study showed that the only complication observed in rt-PA group was cerebral hemorrhage. No other complication was seen in patients under the treatment in this study. No complication was observed in patients of antiplatelet group. Mortality was the same in two groups. It is worth noting that rt-PA dose in this study was 0.9 mg/Kg (maximally 90 mg), ten percent of calculated dose was administered as bolus and the rest was infused within an hour. In our study there was no complications with antiplatelet dual therapy.
Other studies carried out in this regard showed relatively few complications of antiplatelet dual therapy in patients with acute stroke (12, 13). However, the results of this study showed that the increased risk of bleeding in patients undergoing long term treatment with Clopidogrel is one of the main issues in antiplatelet therapy (14).
Overall, the results of different studies showed, increased risk of intracranial hemorrhage. Based on the studies, the careful and conservative selection of patients is aligned with hemorrhage reduction (at the cost of depriving a part of patients from rt-PA treatment). In a double blind clinical trial with the placebo control by Hacke and colleagues, thrombolysis was carried out within 3 to 4.5 hours after stroke using alteplase. This study confirmed intracranial hemorrhage was significantly more reported in patients undergoing treatment with alteplase than in the placebo group. Although they have often been asymptomatic and non-lethal.
Other complications and also the mortality rate between two groups were the same (8). In the double blind clinical trial carried out by the IST–3 collaborative group, patients were randomized to receive rt-PA or placebo. Totally, the results of the study showed that, contrary to the results of the present paper, the risk of intracranial and extra-cranial hemorrhage significantly increased with rt-PA prescription. However, no difference was seen in other complications (15). Along with the results of this research, one study by Tekle et.al. on the treatment outcomes of patients with stroke in different time intervals indicated that the frequency of mortality in rt-PA group during the first three hours was comparable to that in patients undergoing thrombectomy during the first 2.5 to 4 hours (16). Finally, in consistency with the results of the present paper on performed meta-analysis by Wardlaw et al. on 12 studies with sample size of 7012 patients after collecting the overall results of clinical trial mortality showed complications including lethal intracranial hemorrhage (ICH), symptomatic ICH and brain edema revealed no any meaningful mortality difference in rt-PA group in comparing with control group.
Considering the results of previous studies which confirm the safety of rt-PA treatment, with correct choice of patients, the use of this therapeutic approach can be highly recommended.
Another finding of this study was the higher frequency of stroke risk factors in patients who have received only antiplatelet treatment (particularly hypertension). Despite the fact that the blood pressure level was not one of the entry or exit criteria for entering the rt-PA treatment group, the use of this therapy for this group of patients was always disputed. Studies carried out before the drug approval by FDA showed that systolic blood pressure over 185 mmHg and diastolic blood pressure greater than 110 mmHg were associated with an increased risk of symptomatic intracerebral hemorrhage (17). The data from the subsequent studies also accentuated the actual and definite increased risk of symptomatic ICH associated with hypertension (18). Based on a sub analysis of the data on study, it was revealed that high systolic blood pressure was associated with hemorrhagic transformation after rt-PA therapy, which implies that high blood pressure might not be the only cause of symptomatic ICH; however, high blood pressure itself was due to the occurrence of hemorrhage in rt-PA prescription. This probable theory was approved by observing hematoma expansion in the area of high blood pressure created as a result of rt-PA (20).
By comparing patients with placebo and rt-PA, analysis of ECASS-II study data showed that favorable outcome has reverse relationship with the basic systolic blood pressure, the maximum and average of blood pressure over a 24-hour period and also changes in blood pressure level. In a retrospective analysis of SITS-ISTR database, the results indicated that there was a U- shape relationship between blood pressure and the occurrence of symptomatic intracranial hemorrhage and the best results have been observed with 140 mmHg systolic blood pressure. Despite these findings, there is no consensus on intravenous aggressive treatment of high blood pressure in patients with ischemic stroke (to start rt-PA). However, it seems that a group of patients undergoing antiplatelet drug treatment in this study were deprived of rt-PA treatment due to hypertension that this issue happened regardless of the design criteria (based on the physician’s mindset and clinical decision making).