Outcome of stroke patients receiving different doses of recombinant tissue plasminogen activator

Abstract

Background and purpose Intravenous recombinant tissue plasminogen activator (tPA) at a dose of 0.9 mg/kg body weight is associated with a high hemorrhagic transformation (HT) rate. Low-dose tPA (0.6 mg/kg) may have a lower hemorrhage rate but the mortality and disability rates at 90 days cannot be confirmed as non-inferior to standard-dose tPA. Whether the doses 0.7 and 0.8 mg/kg have better efficacy and safety needs further investigation. Therefore, this study is to compare the efficacy and safety of each dose of tPA (0.6, 0.7, 0.8, and 0.9 mg/kg body weight) and to investigate the factors affecting early neurological improvement (ENI) and early neurological deterioration (END). Methods For this observational study, data were obtained from 274 patients who received tPA thrombolytic therapy in Chia-Yi Christian Hospital stroke unit. The tPA dose was given at the discretion of each physician. The definition of ENI was a >8 point improvement (compared with baseline) at 24 h following thrombolytic therapy or an improvement in the National Institutes of Health Stroke Score (NIHSS) to 0 or 1 toward the end of tPA infusion. The definition of END was a >4 point increase in NIHSS (compared with baseline) within 24 h of tPA infusion. The primary objective was to investigate whether 0.7 and 0.8 mg/kg of tPA have higher ENI rate, lower END rate, and better outcome at 6 months. Poor outcome was defined as having a modified Rankin Scale of 3 to 6 (range, 0 [no symptoms] to 6 [death]). The secondary objective was to investigate whether low-dose tPA has a lower risk of intracerebral HT than that with standard-dose tPA. We also investigated the factors affecting ENI, END, HT, and 6-month outcome. Results A total of 274 patients were included during the study period, of whom 260 were followed up for >6 months. There was a trend for the HT rate to increase as the dose increased ( P =0.02). The symptomatic HT rate was not significantly different among the low-dose and standard-dose groups. The ENI and END ( P =0.52) were not significantly different among the four dosage groups. The clinical functional outcome at 6 months after stroke onset was poorer in the standard-dose group ( P =0.02). Stroke severity ( P <0.01), stroke type ( P =0.03), and diabetes mellitus ( P =0.04) affected the functional outcome at 6 months. Conclusion Among the 274 patients receiving tPA thrombolytic therapy, the HT rate increased as dose increased. The symptomatic HT, ENI and END rates were not significantly different among the low-dose (0.6, 0.7, and 0.8 mg/kg) and standard-dose groups. Stroke severity (NIHSS >12), stroke type (cardioembolism and large artery atherosclerosis) and diabetes mellitus were associated with poor outcome at 6 months.

The rate of early neurological deterioration occurring after thrombolytic therapy: A meta‐analysis

“…Eleven studies with a total of 3,539 subjects, including 373 patients with END and 3,166 patients without END, met the inclusion and exclusion criteria. Of these studies, there were 4 studies from Asia (Chi & Chan, 2017;Mori et al, 2012;Ong et al, 2017;Yang et al, 2016), 6 studies from Europe (Fiorelli et al, 1999;Hansen, Christensen, Havsteen, Ovesen, & Christensen, 2018;Seners et al, 2014Seners et al, , 2017Simonsen et al, 2016;Zinkstok et al, 2014), and 1 study from North America (Saqqur et al, 2007). The baseline characteristics of all the included studies were shown in Table 1.…”

“…The baseline characteristics of all the included studies were shown in Table 1. Four studies provided the type and dose of the thrombolytic drug (Fiorelli et al, 1999;Mori et al, 2012;Ong et al, 2017;Yang et al, 2016), and the remaining studies provided insufficient information of the thrombolytic drug (Chi & Chan, 2017;Hansen et al, 2018;Saqqur et al, 2007;Seners et al, 2014Seners et al, , 2017Simonsen et al, 2016;Zinkstok et al, 2014) (Table 2).…”

“…Unfortunately, no definition of END has been unified up to now. Most studies define END as ≥4-point increase in National Institutes of Health Stroke Scale (NIHSS) between admission and 24 hr (Chi & Chan, 2017;Ong, Wong, Wu, & Su, 2017;Seners et al, 2017;Yang et al, 2016). Besides, some different definitions of END have been put forward by researchers.…”

High Neutrophil-to-Lymphocyte Ratio Predicts Hemorrhagic Transformation in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis

“…IVT has been reported to increase the incidence of HT markedly [7]. Atrial fibrillation (AF) [8,9], National Institutes of Health Stroke Scale (NIHSS) score [10], blood glucose level [11], leukoaraiosis [12], dual antiplatelet agent treatment before IVT [13], and systolic blood pressure variability [14] are the predictors of HT after IVT.…”

<p>The Impact of Loading Dose on Outcome in Stroke Patients Receiving Low-Dose Tissue Plasminogen Activator Thrombolytic Therapy</p>

“…[10][11][12] Studies reported that the efficacy and safety of low-dose tPA were comparable with that of standard-dose tPA. [11][12][13][14][15] However, some studies reported that stroke patients receiving standard dose tPA had higher rates of favorable outcome and without significantly increased risk of symptomatic hemorrhage and mortality when compared with those of patients receiving low-dose tPA. [16][17][18] In the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) study, the investigators compared the effect of low-dose (0.6 mg/kg) with standard-dose IV tPA on the outcomes in patients with ischemic stroke.…”