Prospective evaluation of a prostacyclin-sparing aspiring formulation and heparin/warfarin in aspirin users with unstable angina or non-Q wave myocardial infarction at rest

The aim of this trial was to compare the efficacy of combinationantithrombotic therapy with a prostacyclin-sparing aspirin plusanticoagulation versus conventional aspirin plus anticoagulation,when added to antianginal therapy, in patients with unstableangina or non-Q wave myocardial infarction already being treatedwith aspirin. In a double-blind (for the aspirin) study, 144prior aspirin users were randomized; 72 patients received controiled-release,prostacyclin-sparing aspirin 75 mg daily plus anticoagulation(intravenous heparin followed by warfarin to maintain the internationalnormalized ratio at 2–3), and 72 patients received conventionalaspirin 75 mg daily plus the same anticoagulation. Controlled-releaseaspirin was formulated to preserve endothelial cell prostacyclinsynthesis. Trial therapy was begun by 13.2 ± 12.3 h ofqualifying pain, and continued for 12 weeks. The frequency of recurrent angina with electrocardiographicchanges, myocardial infarction, or death, was analysed by intentionto treat. At 12 weeks, events were     

西格列汀对2型糖尿病患者阿司匹林抵抗的影响

目的：研究西格列汀对2型糖尿病(Type 2 diabetes mellitus,T2DM)患者阿司匹林抵抗(aspirin resistance,AR)的影响及其机制。方法：从136例T2DM患者选取68例AR患者,随机分成西格列汀组及二甲双胍组,入组前及治疗过程中检测空腹血糖(fasting plasma glucose,FPG)、糖化血红蛋白(glycated hemoglobin,HbAlc)、高敏C反应蛋白(high-sensitivity C reactive protein,hs-CRP),治疗的第1,3,6,12个月分别检测二磷酸腺苷(adenosine diphosphate,ADP)及花生四烯酸(arachidonic acid,AA)诱导的血小板聚集率(platelet aggregation,PAG),评价西格列汀对AR的影响。 结果：经降糖治疗6个月后,两组患者FPG和HbAlc基本达标,降糖效果差异无统计学意义(P>0.05),但西格列汀组患者hs-CRP,ADP及AA诱导的PAG明显下降,与二甲双胍组比较差异有统计学意义(P<0.05)。结论：西格列汀能显著改善T2DM患者的氧化应激炎症状态及AR,且AR的改善可能不依赖于血糖的降低。     

阿司匹林增加高脂喂养Wistar大鼠胰岛素敏感性和Mfn2mRNA的表达

目的 研究阿司匹林对高脂喂养Wistar大鼠胰岛素敏感性和线粒体功能的影响。方法 24只Wistar大鼠,♂,分为对照组(NC)、高脂组(HF)和阿司匹林组(AF)(n=8),喂养8周后,以高胰岛素-正常葡萄糖钳夹测定大鼠胰岛素敏感性,取空腹血清测定大鼠谷草转氨酶(ALT)、谷丙转氨酶(AST)、高密度脂蛋白(HDL-C)、甘油三酯(TG)、空腹血糖(FBS),空腹胰岛素(FINS)的水平;将大鼠肝脏组织进行固定、包埋、切片和HE染色,观察肝脏组织学变化;取肝脏组织,测定肝糖原含量;提取肝细胞线粒体并分离线粒体超氧化物歧化酶,测定线粒体超氧化物歧化酶活性(SOD),以及提取肝组织总RNA,应用RT-PCR测定肝脏组织Mfn2 mRNA的表达。结果 与NC组大鼠比较,HF组大鼠肝脏指数、TG、FBS、ALT、AST、INS明显升高(P<0.05),GIR和SOD显著降低(P<0.05),肝脏组织Mfn2 mRNA表达显著降低,肝细胞体积增大,胞质中有脂滴空泡;AF组大鼠上述各指标差异无统计学意义,显微结构无显著变化。结论 阿司匹林可以改善高脂诱导的胰岛素抵抗及抑制脂肪肝的形成,这一作用可能是部分通过促进肝细胞Mfn2表达、改善线粒体功能实现的。     

Effects of lysine aspirin on lung AQP5 expression and lymphocyte apoptosis in paraquat-poisoned rats

Objective: This study explored the effects of lysine aspirin on lung aquaporin 5 (AQP5) expression and lymphocyte apoptosis in paraquat-poisoned rats. Methods: Thirty healthy male Wales rats were randomly divided into three groups (n?=?10): the control group received 0.9% sodium chloride (0.4?mL, intragastric administration; 0.8?mL, intraperitoneal injection); the paraquat group received 40?mg/kg paraquat (intragastric administration) and 0.9% sodium chloride (intraperitoneal injection); and the paraquat + lysine aspirin group received 40?mg/kg paraquat (intragastric administration) and 20?mg/kg lysine aspirin (intraperitoneal injection). Rats were killed at 24 and 48?h. RT-PCR and immunohistochemical staining were performed in lung tissue to determine the AQP5 mRNA and protein expression. Blood from the arterial vein was used to evaluate lymphocyte apoptosis. Results: The lung tissue of paraquat-treated rats displayed pulmonary hemorrhage, interstitial edema and inflammatory cell infiltration. AQP5 mRNA and protein expression in the paraquat-treated group decreased after 24 and 48?h, whereas the peripheral blood lymphocyte apoptosis ratio significantly increased. In contrast, paraquat + lysine aspirin treatment ameliorated these changes. Conclusion: Paraquat decreases AQP5 expression in rat lungs and increases peripheral blood lymphocyte apoptosis. Lysine aspirin can reduce these alterations.     

Improving the Gastrointestinal Tolerability of Aspirin in Older People

Interventions to reduce mortality and disability in older people are vital. Aspirin is cheap and effective and known to prevent cardiovascular and cerebrovascular disease, many cancers, and Alzheimer dementia. The widespread use of aspirin in older people is limited by its gastrointestinal side effects. Understanding age-related changes in gastrointestinal physiology that could put older people at risk of the side effects of aspirin may direct strategies to improve tolerance and hence lead to greater numbers of older people being able to take this effective intervention.     

Should patients with hypertension receive antithrombotic therapy?

The main complications of hypertension, i.e. coronary heart disease, ischaemic strokes and peripheral vascular disease (PVD), are usually related to thrombosis. Increasing evidence also suggests that hypertension fulfils the components of Virchow's triad, thus conferring a prothrombotic or hypercoagulable state, as evident by abnormalities of haemostasis, platelets and endothelial function. It therefore seems plausible that use of antithrombotic therapy may help prevent these thrombosis-related complications of hypertension. Indeed, hypertensive patients with an estimated 10-year CHD risk > or = 15% will have their cardiovascular risk reduced by 25% using antihypertensive treatment, but the addition of aspirin further reduces major cardiovascular events by 15%. Recent guidelines recommend the use of aspirin 75 mg daily for hypertensive patients who have no contraindication to aspirin, in one of the following categories: (i) secondary prevention - cardiovascular complications (myocardial infarction, angina, non-haemorrhagic stroke, peripheral vascular disease or atherosclerotic renovascular disease); and (ii) primary prevention - those with blood pressure controlled to < 150/90 mmHg and one of: (a) age > or = 50 years and target organ damage (e.g. LVH, renal impairment, or proteinuria); (b) a 10-year CHD risk > or = 15%; or (c) type II diabetes mellitus. However, some of the risks of aspirin administration, namely increased incidence of major bleeding events, may possibly outweigh the benefits, especially in low-risk individuals.     

Aspirin withdrawal in patients treated with ticagrelor presenting with non‐ST elevation myocardial infarction

Essentials

• Strong P2Y₁₂ blockade may cause platelet inhibition that is only minimally enhanced by aspirin.
• We evaluated aspirin withdrawal on platelet reactivity in ticagrelor treated patients.
• Aspirin withdrawal resulted in increased platelet reactivity to arachidonic acid.
• Aspirin withdrawal caused little difference in adenosine diphosphate‐induced platelet aggregation.

Summary

Background

Recent studies have shown that the thromboxane A₂‐dependent pathway is dependent on the ADP–P2Y₁₂ pathway, and that strong P2Y₁₂ receptor blockade alone causes inhibition of platelet aggregation that is minimally enhanced by aspirin. Data from the PLATO trial suggested that, among ticagrelor‐treated patients, high‐dose versus low‐dose (< 100 mg day^?1) aspirin is associated with an increased risk fof ischemic events.

Objectives

To evaluate the impact of aspirin withdrawal on platelet reactivity in acute coronary syndrome (ACS) patients treated with a potent P2Y₁₂ blocker.

Patients/Methods

This was a current prospective, randomized, placebo‐controlled, double‐blind, cross‐over study. The study population comprised 22 consecutive ACS patients who underwent percutaneous coronary intervention and were treated with aspirin (100 mg day^?1) and ticagrelor. Thirty days post‐ACS, open‐label aspirin was stopped, and patients were randomized to either blinded aspirin or placebo for 2 weeks, with each patient crossing over to the other arm for an additional 2 weeks. Platelet reactivity to arachidonic acid and ADP determined with light‐transmission aggregometry (LTA) and VerifyNow was evaluated at baseline, and 2 weeks and 4 weeks later.

Results

Aspirin withdrawal resulted in an increase in arachidonic‐acid induced platelet reactivity as determined with both LTA (77.0% ± 11.3% versus 20.8% ± 4.4%) and VerifyNow (607.7 ± 10.6 aspirin reaction units [ARU] versus 408.5 ± 14.4 ARU). Platelet response to ADP, as determined with both LTA and VerifyNow, did not differ with either aspirin or placebo (32.9% ± 2.6% versus 35.8% ± 3.6%, and 33.5 ± 6.4 P2Y₁₂ reaction units (PRU) versus 29.6 ± 5.7 PRU, respectively).

Conclusions

Aspirin withdrawal early post‐ACS results in increased platelet reactivity in response to arachidonic acid, despite concomitant treatment with the potent P2Y₁₂ blocker ticagrelor.

     

Clopidogrel Versus Aspirin for the Treatment of Acute Coronary Syndrome After a 12-Month Dual Antiplatelet Therapy: A Cost-effectiveness Analysis From China Payer's Perspective

Purpose

Monotherapy with either aspirin or clopidogrel is recommended for long-term use after discontinuation of dual-antiplatelet therapy (DAPT) for acute coronary syndrome (ACS) management after percutaneous coronary intervention (PCI). The present study is to evaluate the cost-effectiveness of clopidogrel versus aspirin after 12-month DAPT for patients with ACS who underwent PCI in China.

低剂量阿司匹林对高危孕妇子痫前期的预防效果

目的：评价低剂量阿司匹林（ LDA）在预防高危孕妇子痫前期（ PE）的作用及疗效。方法采用随机、对照、双盲实验将480名12周及20周孕妇分为12个组别,分别给予50mg／d、100mg／d及150mg／d剂量的LAD和安慰剂,比较各组间的子痫发生情况、分娩孕周、孕妇产后出血量、早产及胎儿生长受限、新生儿出血性疾病发生、新生儿死亡率等情况。观察合适的服用LDA的时间和剂量。结果12周与20周孕妇不同剂量LDA组结果均显示,服用LDA的子痫发生率均低于服用安慰剂组,而且以100mg／d组别子痫发生率最低,差异具有统计学意义（χ2＝29．838,P＜0．05）;12周结果显示早产发生、新生儿出血性疾病发生情况方面,服用LDA与服用安慰剂均无统计学差异（χ2值分别为1．441、1．034,均P＞0．05）;但是服用LDA组发生胎儿生长受限及新生儿死亡情况显著低于服用安慰剂组,且差异有统计学意义（χ2值分别为13．317、15．984,均P＜0．05）。20周结果显示在早产发生、胎儿生长受限、新生儿出血性疾病发生情况方面,服用LDA与服用安慰剂并无统计学差异（χ2值分别为1．441、6．117、0．835,均P＞0．05）;但是服用LDA组发生新生儿死亡情况显著低于服用安慰剂组,且差异有统计学意义（χ2＝15．984,P＜0．05）;12孕周服用LDA各组较20孕周服用LDA各组的子痫发生率低显著降低（χ2＝11．663,P＜0．05）。结论12周服用LDA100mg／d可以有效降低PE的发生,具有预防效果。     

Effects of hemorrhagic shock, aspirin, and ethanol on secretagogue-induced experimental pancreatitis

The effects of hemorrhagic shock, aspirin, and ethanol on the biochemical and morphologic changes of experimental pancreatitis were evaluated. Pancreatitis was induced by infusing rats with a supramaximally stimulating dose (5 μg/kg/h) of caerulein. Hemorrhagic shock was established by removing sufficient blood to reduce mean arterial pressure by 30%, where it was maintained for 30 min. Aspirin (25 mg/kg) and ethanol (2 g/kg) were administered through an orogastric tube at 8-h intervals for 48 h. Hemorrhagic shock did not alter the degree of hyperamylasemia, pancreatic edema, cathepsin subcellular redistribution, or in vitro LDH leakage that characterize this model of pancreatitis. Hemorrhagic shock did, however, worsen the morphologic evidence of pancreatic injury. Administration of aspirin with ethanol did not alter the degree of hyperamy-lasemia, pancreatic edema, or subcellular cathepsin redistribution. Aspirin-ethanol pretreatment also did not alter the morphologic severity of pancreatitis.