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Beneficial Effect of Beraprost Sodium Plus Aspirin in the Treatment Of DRUG CONTROLLED STUDIES e-ISSN 1643-3750 © Med Sci Monit, 2017; 23: 4401-4407 DOI: 10.12659/MSM.902825 Received: 2016.12.14 Accepted: 2017.03.06 Beneficial Effect of Beraprost Sodium Plus Published: 2017.09.12 Aspirin in the Treatment of Acute Ischemic Stroke Authors’ Contribution: ABCDEF 1 Siqia Chen* 1 Department of Neurology, First Affiliated Hospital of Shantou University Medical Study Design A BCDF 1 Sisi Xie* College, Shantou, Guangdong, P.R. China Data Collection B 2 Department of Pharmacy, First Affiliated Hospital of Shantou University Medical Statistical Analysis C ADEFG 1 Wenzhen He College, Shantou, Guangdong, P.R. China Data Interpretation D BCD 2 Duncan Wei Manuscript Preparation E BC 1 Shunxian Li Literature Search F Funds Collection G BC 1 Wenjie Chen * These Authors equally contributed to the work Corresponding Author: Wenzhen He, e-mail: [email protected] Source of support: Departmental sources Background: To investigate the combination of beraprost sodium (BPS) and aspirin in the treatment of acute ischemic stroke (AIS). Material/Methods: 308 patients with acute cerebral infarction were randomly divided into two groups: experimental group (n=154), treated with BPS (40 μg, tid) and aspirin (100 mg, qd); control group (n=154), treated with 100 mg of aspirin, qd). The antiplatelet therapy remained unchangeable until six months after hospital discharge. Results: Initially, no significant differences were found between the two groups. After six months, the relapse-free sur- vival rate was similar between the treatment group (98.1%) and the control group (97.4%). One patient died from AIS in the control group. However, glomerular filtration rate was significantly higher; neurological function and functional ability of patients were better in patients treated with BPS plus aspirin (experimental group) than that in aspirin alone group. No significant difference was found in the function of the coagulation system, suggesting that BPS plus aspirin treatment did not increase the risk of bleeding. Serious adverse events did not occur in both groups. Facial flushing (one case) and mild gastrointestinal reaction (one case) were found in the treatment group without influencing treatment. Conclusions: In our trial involving patients with acute cerebral infarction, BPS plus aspirin was not found to be superior to aspirin in reducing the recurrence of cerebral infarction or death. However, BPS plus aspirin treatment could improve renal function and neurological function without increasing the risk of bleeding. MeSH Keywords: Nervous System Diseases • Nontherapeutic Human Experimentation • Stroke Full-text PDF: https://www.medscimonit.com/abstract/index/idArt/902825 1844 6 4 15 Indexed in: [Current Contents/Clinical Medicine] [SCI Expanded] [ISI Alerting System] This work is licensed under Creative Common Attribution- [ISI Journals Master List] [Index Medicus/MEDLINE] [EMBASE/Excerpta Medica] NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) 4401 [Chemical Abstracts/CAS] [Index Copernicus] Chen S. et al.: DRUG CONTROLLED STUDIES BPS plus aspirin in acute ischemic stroke © Med Sci Monit, 2017; 23: 4401-4407 Background disorder, patients with hemorrhage in digestive tract or other parts of the body, patients with severe liver and renal insuffi- Acute ischemic stroke (AIS) causes high morbidity and mor- ciency, and patients with malignant tumor, trauma, or surgery. tality, and also has a high recurrence rate. Secondary preven- The inclusion and exclusion criteria are listed in Table 1. The tion in patients with first onset ischemic stroke is extremely study was approved by the Institutional Ethics Committee, and important. The initiation of antiplatelet therapy immediately informed consent was obtained from all patients. after AIS is widely applied to prevent the recurrence and pro- gression of the disease and also reduce the incidence of oth- Treatment er vascular events [1]. Besides the hemorrhagic complications associated with antiplatelet therapy, aspirin monotherapy dose The 308 patients with acute cerebral infarction were random- not significantly reduce stroke progression [2]. Even though the ly divided into two groups: the experimental group (n=154), combination antiplatelet therapy might reduce the recurrence treated with BPS (40 μg, tid) and aspirin (100 mg, qd); and and stroke progression in large artery disease [3,4], increased the control group (n=154), treated with 100 mg of aspirin, bleeding complications minimize the benefit from antithrom- qd). All patients were treated with aspirin within 72 hours af- botic therapy and poses a great challenge. The pathophysiol- ter the onset of cerebral infarction. The antiplatelet therapy ogy of AIS is very complex, and patients with AIS often suf- remained unchanged till six months after hospital discharge. fer from other vascular diseases such as renal diseases and Besides the antiplatelet treatment, patients received regular myocardial disease. Thus, it is especially important to devel- treatments such as lipid regulation, free radical scavenging (30 op new treatment combinations which can also improve neu- mg of edaravone, intravenously, bid) and regulation of blood rological function and protect other organic functions, beyond pressure and blood glucose. The average hospitalization days preventing ischemic stroke recurrence. for each group were 14.2±3.5 days. Beraprost sodium (BPS), a stable synthetic and orally active pros- Study design and biochemical analysis tacyclin (PGI2) analogue, can inhibit platelet aggregation mediat- ed by cAMP, and can also inhibit vasoconstriction and leukocyte The levels of serum creatinine (Cr), prothrombin time (PT), ac- chemotaxis [5,6]. BPS has been reported to prevent microcir- tivated partial thromboplastin time (APTT), and fibrinogen (Fib) culatory derangement in the acute stage of ischemic stroke in were measured at admission, and at two weeks, one month, rat [7], and also has renal and neurological protective roles [8– and six months of treatment. The National Institute of Health 10]. Considering the comprehensive role of BPS in inhibition of Stroke Scale (NIHSS) was used to evaluate neurological func- platelet aggregation and protective roles in renal and neurologi- tion after anterior circulation infarction (ACI). Functional abil- cal function, we hypothesized that the combination of BPS with ities of stroke patients were recorded using the Barthel index aspirin may exert potent anti-platelet effects and improve renal (BI) at admission and during follow-up. The adverse effects and neurological function in patients with acute ischemic stroke. were also recorded. Glomerular filtration rate was calculated using the simplified MDRD equation: In the present study, we recruited 308 patients with acute isch- emic stroke; these patients were randomly treated with BPS GFR (mL/min/1.73m2)=186×(Scr)–1.154×(age)–0.203×(0.742 female) plus aspirin or aspirin alone. The therapeutic efficacy, adverse effects, and renal and neurological outcomes were reported. Statistical analysis Statistical analysis is processed by SPSS 18.0, and quantitative Material and Methods data are presented by mean ± standard deviation (mean ±SD). Repeated measures analysis of variance was used to compare Patients the differences between the two groups. Relapse-free survival rate was compared by Kaplan-Meier test. Probability value of In all, 308 patients with acute ischemic stroke were recruited p<0.05 was considered to be significantly different. for a double-blind trial of antiplatelet therapy using combina- tion of beraprost sodium (BPS) and aspirin versus aspirin alone. Patients were included based on the following criteria: 1) pa- Results tients suffered from large-artery atherosclerosis (LA) and small- artery occlusion lacunar (SA) according to the TOAST classifica- Initial patient characteristics tion for ischemic stroke; 2) first onset of stroke and admitted to our hospital; and 3) treated within 72 hours after the onset At onset of the study, no significant difference existed in -pa of cerebral infarction. We excluded patients with coagulation tient characteristics such as age, gender distribution, and Indexed in: [Current Contents/Clinical Medicine] [SCI Expanded] [ISI Alerting System] This work is licensed under Creative Common Attribution- [ISI Journals Master List] [Index Medicus/MEDLINE] [EMBASE/Excerpta Medica] NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) 4402 [Chemical Abstracts/CAS] [Index Copernicus] Chen S. et al.: BPS plus aspirin in acute ischemic stroke DRUG CONTROLLED STUDIES © Med Sci Monit, 2017; 23: 4401-4407 Table 1. Characteristics of participants at the onset of ACI. Parameter Treatment group (n=154) Control group (n=154) t/c2 p Value Age (years) 66.6±12.1 67.1±11.5 0.37 0.71 Gender Male 94 90 0.12 0.73 Female 60 64 BMI 22.53±3.86 22.46±3.92 0.16 0.87 Hypertension 115 105 1.29 0.26 Diabetes 55 46 0.94 0.33 Blood lipids TC 5.15±1.41 5.41±1.35 1.65 0.09 LDL 3.37±0.90 3.63±1.25 1.48 0.23 HDL 1.23±0.29 1.12±0.41 2.40 0.13 Smoking 40 36 0.16 0.69 Alcohol use 19 21 0.029 0.87 Coronary disease 15 12 0.16 0.69 TOAST classification LA 72 65 0.47 0.49 SA 82 89 Embolic stroke 35 28 Thrombotic stroke 119 126 NIHSS score 4.66±3.58 4.99±3.47 0.82 0.41 BI 82.02±16.72 80.39±16.76 0.243 0.62 LA – large-artery atherosclerosis; SA – small-artery occlusion lacunar. body mass index (BMI) as shown in Table 1. The treatment group (98.1%) and the control group (97.4%) (Table 2, Figure 1). group includes 154 patients (male, 94), with the average age One patient died from AIS in the control group. of 66.6±12.1 years (range: 40–80 years). The control group also contains 154 patients (male, 90), with the average age Renal function, neurological function, and functional of 66.6±12.167.1±11.5 years (range: 40–85 years). The distri- abilities during follow-up bution of patients with hypertension, diabetes, and coronary disease was similar when comparing the two groups (Table 1).
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