脑梗死急性期阿司匹林和氯吡格雷双联抗血小板疗效观察

目前我国的脑血管病的死亡率已经超过心血管病成为第一死因,而缺血性脑卒中占卒中总数的80%。众所周知,抗血小板治疗是脑梗死急性期基本用药之一。本文旨在探讨治疗脑梗死急性期,传统单用阿司匹林和阿司匹林联合氯吡格雷的疗效观察进行比较。为此,我们对住院的脑梗死患者进行了相关研究。     

阿司匹林联合氯吡格雷双联抗血小板治疗对老年冠心病的临床疗效

目的探讨阿司匹林联合氯吡格雷双联抗血小板治疗对老年冠心病的有效性与安全性。方法选取2010年6月—2012年6月我院收治的老年冠心病患者140例,按照就诊顺序将其分为试验组与对照组,各70例。两组患者均行常规药物治疗,在此基础上对照组患者口服阿司匹林,试验组患者在对照组基础上口服氯吡格雷,均治疗6个月。治疗前,治疗后1、3、6个月均行空腹静脉血检测,测定并记录患者血小板计数、血小板凝聚率、凝血指标,治疗期间观察出血事件发生情况。结果两组患者治疗前后血小板计数、PT、APTT、纤维蛋白原(FIB)及治疗期间出血事件发生率比较,差异均无统计学意义(P0.05);治疗后3、6个月试验组血小板凝聚率低于对照组(P0.05)。结论阿司匹林联合氯吡格雷双联抗血小板治疗对老年冠心病效果明显优于阿司匹林单药治疗,能有效降低血小板凝聚率。     

阿司匹林和氯吡格雷抵抗现象的研究进展

阿司匹林联合氯吡格雷是目前最常用的抗血小板治疗方案,但在临床上有部分患者接受抗血小板药物治疗后仍有不良心血管事件发生。现主要介绍近年来关于阿司匹林和氯吡格雷＂抵抗＂机制的研究进展,并对目前临床上可能采取的有效预防措施进行探讨。     

阿司匹林和氯吡格雷抵抗的研究进展

近来阿司匹林和氯吡格雷抵抗受到了越来越多的关注,它被用来描述冠状动脉疾病患者在用阿司匹林和氯吡格雷抗血小板治疗后仍发生不良心血管事件。明确抵抗的原因和机制将使冠状动脉疾病患者受益匪浅。现就阿司匹林和氯吡格雷抵抗的定义、可能机制和检测方法做一综述。     

阿司匹林和氯吡格雷抵抗的处理对策

阿司匹林和氯吡格雷是临床上应用最广泛的抗血小板聚集药物,但有些患者接受抗血小板聚集药物治疗,仍有心肌梗死、猝死等不良事件发生。因此,正确识别、及时处理其抵抗具有重要的临床意义。现就对阿司匹林和氯吡格雷抵抗的定义,检测方法,处理对策做一综述。     

氯吡格雷联合阿司匹林治疗糖尿病并发急性脑梗死的临床研究

目的探讨氯吡格雷联合肠溶阿司匹林治疗糖尿病并发急性非心源性脑梗死的早期疗效和安全性。方法选择90例糖尿病并发首次非心源性急性脑梗死的患者,随机分为治疗组(45例)和对照组(45例)。治疗组给予氯吡格雷联合肠溶阿司匹林治疗,对照组给予肠溶阿司匹林治疗,分别在治疗前后进行临床疗效评定、神经功能缺损评分(NDS)及发生出血不良反应统计。结果在糖尿病并发急性非心源性脑梗死的早期治疗中,两组临床疗效比较和神经功能缺损评分比较有统计学意义(P0.05);两组均无发生脑出血,两组不良反应比较差异无统计学意义(P0.05)。结论氯吡格雷联合肠溶阿司匹林在糖尿病并发急性非心源性脑梗死的早期治疗中疗效显著,优于单用肠溶阿司匹林,且不良反应轻,出血发生率低,值得临床推广应用。     

氯吡格雷改善高血压病高危患者阿司匹林抵抗的临床研究

目的 研究氯吡格雷对高血压病高危阿司匹林抵抗患者的治疗价值.方法 525例高血压病高危患者依照血小板聚集率分为阿司匹林敏感者和阿司匹林抵抗者,将114例阿司匹林抵抗者随机分为单用阿司匹林治疗组和氯吡格雷联合阿司匹林治疗组,411例阿司匹林敏感者中随机选取40例设为对照组.三组患者给予严格的药物治疗后随访一年,观察阿司匹林治疗组和联合治疗组患者在治疗前后的血小板聚集率变化,以及三组患者治疗后缺血性心脑血管病的发生率和出血性事件的发生率.结果 氯吡格雷可以有效地降低阿司匹林抵抗患者的血小板聚集率(P＜0.01);较少发生缺血性心脑血管病(P＜0.01),而不增加出血事件的发生(P＞0.05).结论 氯吡格雷与阿司匹林联用安全,且能提高阿司匹林抵抗患者的临床疗效.     

氯吡格雷联合阿司匹林治疗稳定型心绞痛伴糖尿病的疗效观察

目的 观察氯吡格雷联合阿司匹林治疗稳定型心绞痛伴糖尿病的疗效.方法 资料选取该院2013年3月-2014年3月收治的稳定型心绞痛伴糖尿病患者共114例,随机分为研究组与对照组;研究组57例予氯吡格雷联合阿司匹林治疗,对照组57例予阿司匹林治疗;观察治疗前后血小板聚集情况、临床症状及心绞痛发病次数.结果 治疗1 w后,研究组血小板聚集率降幅显著高于对照组(P＜0.05),比较差异明显具统计学意义;治疗后研究组ST变化(2.12±0.51)mm,FIB水平(4.87±1.11)g/L,均显著优于对照组,比较差异明显具统计学意义(P＜0.05);治疗后研究组心绞痛发作(3.09±1.24)次,显著低于对照组的(5.64±2.31)次,比较差异明显具统计学意义(P＜0.05).结论 氯吡格雷联合阿司匹林治疗稳定型心绞痛伴糖尿病临床疗效显著,具实际应用价值.     

氯吡格雷和阿司匹林合用与单用阿司匹林治疗心力衰竭引起血小板聚集的结果

充血性心力衰竭 (CHF)是西方国家最常见死因之一 ,血栓是CHF常见并发症 ,严重CHF病人每年中风危险率以 4%的速度增长 ,氯吡格雷 (clopidogrel)是一种新的血小板二磷酸腺苷(ADP)受体拮抗剂 ,能减少中风、心肌缺血、心血管死亡发病率 ,对CHF病人 ,ADP受体拮抗剂是否抑制血小板功能不很清楚 ,本文对CHF伴血小板活性增强病人合用氯吡格雷和阿司匹林与单用阿司匹林的抗血小板特性进行了评估。研究对象为美国Baltimore城 88名心血管门诊CHF病人 ,所有病人左室射血分数 <40 %或收缩性CHF ,纽约心脏功能分级Ⅱ Ⅳ级 ,病人血小板活性增…     

阿司匹林与氯吡格雷联合抗血小板治疗不稳定型心绞痛临床疗效观察

目的观察阿司匹林与氯吡格雷联合应用抗血小板聚集治疗不稳定型心绞痛(UAP)临床疗效和安全性。方法选择62例UAP患者,随机分成治疗组与对照组,各31例。治疗组在常规抗凝、抗缺血等治疗基础上,联合应用阿司匹林与氯吡格雷抗血小板聚集治疗;对照组在常规抗凝、抗缺血等治疗基础上,单用阿司匹林抗血小板聚集治疗。随访6个月,评价心绞痛、心电图改善情况及心脏血管事件发生率。结果治疗组总有效率94%,对照组71%,且治疗组心脏血管事件发生率明显降低,两组差异有统计学意义(P<0.05)。结论阿司匹林与氯吡格雷联合应用抗血小板聚集治疗UAP,可改善心绞痛症状,降低心血管事件发生率,出血风险小。     

Prevalence of aspirin resistance in patients with type 2 diabetes

Abstract Aspirin resistance has been recognised to occur in patients with cardiovascular disease and is associated with poor clinical prognosis. The purpose of the present study was to evaluate the prevalence of aspirin resistance in 172 patients with diabetes mellitus type 2 (DM-2). Platelet function of 172 consecutive patients with type 2 diabetes on chronic aspirin therapy was evaluated. The effect of aspirin was assessed using the platelet function analyser (PFA-100) system, reporting platelet-dependent thrombus formation as the time required to close a small aperture in a biologically active membrane. Resistance to aspirin was defined as a normal collagen/epinephrine-induced closure time (82–165 s). Aspirin responders were defined when closure time was 300 s. Thirty-seven (21.5%) of the type 2 diabetic patients were found to be resistant to chronic aspirin therapy, 29 (16.9%) were semi-responders and 106 (61.6%) were responders. Univariate analysis revealed that aspirin non-responders were significantly younger (p<0.05) compared to aspirin responders. A significant number of type 2 diabetic patients are resistant to aspirin therapy. Aspirin resistance can be evaluated by point-of-care testing and should be recognised in diabetic patients that are treated for primary or secondary prevention.     

Determinants of aspirin resistance in patients with type 2 diabetes

BackgroundCardiovascular disease is a leading cause of mortality among patients with type 2 diabetes mellitus (T2DM). Numerous patients with T2DM show resistance to aspirin treatment, which may explain the higher rate of major adverse cardiovascular events observed compared with non-diabetes patients, and it has recently been shown that aspirin resistance is mainly related to accelerated platelet turnover with persistent high platelet reactivity (HPR) 24 h after last aspirin intake. The mechanism behind HPR is unknown. The aim of this study was to investigate the precise rate and mechanisms associated with HPR in a population of T2DM patients treated with aspirin.MethodsIncluded were 116 consecutive stable T2DM patients who had attended our hospital for their yearly check-up. HPR was assessed 24 h after aspirin intake using light transmission aggregometry (LTA) with arachidonic acid (AA) and serum thromboxane B2 (TXB2) measurement. Its relationship with diabetes status, insulin resistance, inflammatory markers and coronary artery disease (CAD) severity, using calcium scores, were investigated.ResultsUsing LTA, HPR was found in 27 (23%) patients. There was no significant difference in mean age, gender ratio or cardiovascular risk factors in patients with or without HPR. HPR was significantly related to duration of diabetes and higher fasting glucose levels (but not consistently with HbA_1c), and strongly related to all markers of insulin resistance, especially waist circumference, HOMA-IR, QUICKI and leptin. There was no association between HPR and thrombopoietin or inflammatory markers (IL-6, IL-10, indoleamine 2,3-dioxygenase activity, TNF-α, C-reactive protein), whereas HPR was associated with more severe CAD. Similar results were found with TXB2.ConclusionOur results reveal that ‘aspirin resistance’ is frequently found in T2DM, and is strongly related to insulin resistance and severity of CAD, but weakly related to HbA_1c and not at all to inflammatory parameters. This may help to identify those T2DM patients who might benefit from alternative antiplatelet treatments such as twice-daily aspirin and thienopyridines.     

老年2型糖尿病合并冠心病患者阿司匹林抵抗的危险因素分析

目的 研究老年T2DM合并冠心病患者对阿司匹林的反应性及其危险因素. 方法 选择我院老年科住院的T2DM合并冠心病患者147例,根据血栓弹力图（TEG）结果将其分为阿司匹林抵抗组（AR,抑制率≤50％）和阿司匹林非抵抗组（N-AR）,并分析两组临床数据. 结果 AR组30例,N-AR组117例.AR发生率为20％.AR组同型半胱氨酸（Hcy）、FPG、TG、LDL-C及HbA1c分别为（16.43±4.77）mmol/L,（7.73±0.16）mmol/L,（1.70±0.60） mmol/L,（2.60±0.55） mmol/L,（7.79±0.58）％,均明显高于N-AR组,而视黄醇结合蛋白（RBP）为（34.17±9.30） mmol/L,低于NAR组（P＜0.05）.Logistic回归分析结果显示,FPG、TC、LDL-C和Hcy是AR的影响因素,使患者AR的危险性分别提高1.9倍,0.1倍,13.1倍和1.1倍.血糖不达标者、糖尿病病程较长者AR发生率增高（P＜0.05）.结论 T2DM合并冠心病患者存在一定的AR现象,有效地控制血糖,减低血脂,降低Hcy,可降低AR发生率.     

Clinical importance of aspirin and clopidogrel resistance

Aspirin and clopidogrel are important components of medical therapy for patients with acute coronary syndromes, for those who received coronary artery stents and in the secondary prevention of ischaemic stroke. Despite their use, a significant number of patients experience recurrent adverse ischaemic events. Interindividual variability of platelet aggregation in response to these antiplatelet agents may be an explanation for some of these recurrent events, and small trials have linked "aspirin and/or clopidogrel resistance", as measured by platelet function tests, to adverse events. We systematically reviewed all available evidence on the prevalence of aspirin/clopidogrel resistance, their possible risk factors and their association with clinical outcomes. We also identified articles showing possible treatments. After analyzing the data on different laboratory methods, we found that aspirin/clopidogrel resistance seems to be associated with poor clinical outcomes and there is currently no standardized or widely accepted definition of clopidogrel resistance. Therefore, we conclude that specific treatment recommendations are not established for patients who exhibit high platelet reactivity during aspirin/clopidogrel therapy or who have poor platelet inhibition by clopidogrel.     

Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions

Aim Our aim was to evaluate the early efficacy and variabilityof the platelet inhibition exerted by 300 mg clopidogrel forthe purpose of acute percutaneous coronary interventions usingplatelet function tests. Methods and results Elective percutaneous coronary interventionwas used as a timely model in which clopidogrel was added toongoing acetylsalicylic acid (aspirin) (100 mg/day) at 2.5 hprior to procedure. Blood samples were collected before administrationof clopidogrel and immediately before the intervention from50 patients. Platelet functions were assessed with traditionalaggregation and PFA-100^®. At baseline, 14 (28%) patients were poor responders to aspirinaccording to PFA and 9 (18%) continued to show arachidonic acid-inducedaggregation. After clopidogrel ADP-triggered aggregation wasonly modestly inhibited in 40% of the patients. Eight percentof the study population was left without any measurable antiplateleteffect. The patients with modest response to clopidogrel hadhigher levels of c-peptide (1.5 nmol/L) than the ones respondingwell (0.9 nmol/L, ). Conclusion Neither ongoing aspirin treatment nor added clopidogreldid reach an expected extent of platelet inhibition. This studyshows that aspirin-treated patients undergoing PCI gain highlyvariable levels of platelet inhibition with short-term clopidogrel300 mg. At 2 h after adding clopidogrel it failed to enhance platelet inhibition in 40% of the patients.In future, targeted platelet function tests may be helpful toindividually select an effective antiplatelet medication forthese patients. This study suggests that for acute PTCA clopidogreldoes not reach the optimal antithrombotic efficacy in all patients.     

老年2型糖尿病患者阿司匹林抵抗的发生率及相关危险因素分析

目的 评价老年2型糖尿病患者阿司匹林抵抗的发生率及可能的危险因素.方法 140例老年2型糖尿病患者,年龄60～92岁,平均(73.8±8.0)岁,口服阿司匹林(≥75 mg)1个月以上.血小板聚集功能采用血小板聚集试验(LTA)和血栓弹力图法(TEG)评价.结果 LTA法检测6例(4.3%)患者为阿司匹林抵抗,44例(31.4%)患者为阿司匹林半抵抗.TEG法检测31例(22.1%)患者为阿司匹林抵抗,其中LTA法显示3例.经TEG法检测分组多因素回归分析结果显示,女性(OR=5.54,95%CI:1.17～27.47,P=0.036)、同型半胱氨酸水平(OR=1.15,95%CI:1.00～1.35,P=0.043)为阿司匹林抵抗的危险因素.结论 老年2型糖尿病患者阿司匹林抵抗发生率较高,阿司匹林抵抗更易发生在女性、高同型半胱氨酸水平的患者.     

Non-HDL cholesterol is an independent risk factor for aspirin resistance in obese patients with type 2 diabetes

Objective

We evaluated the prevalence of aspirin resistance and predictive factors for aspirin resistance in Korean type 2 diabetes patients.

Approach and results

A total of 1045 type 2 diabetes patients from 11 hospitals who were taking aspirin (100 mg/day for ≥2 weeks) and no other antiplatelet agents were studied to evaluate aspirin resistance. Aspirin resistance was measured in aspirin reaction units using VerifyNow^®. Aspirin resistance was defined as ≥550 aspirin reaction units.Aspirin resistance was detected in 102 of the 1045 subjects (prevalence 9.8%). Aspirin resistance was associated with total cholesterol (P = 0.013), LDL-cholesterol (P = 0.028), and non-HDL cholesterol (P = 0.008) concentrations in univariate analysis. In multivariate logistic regression analysis, only non-HDL cholesterol was associated with aspirin resistance in obese (BMI >25 kg/m²) type 2 diabetes patients (adjusted odds ratio 3.55, 95% CI: 1.25–10.05, P = 0.017).

Conclusions

The prevalence of aspirin resistance in Korean type 2 diabetes patients is 9.8%. Non-HDL cholesterol is an independent risk factor for aspirin resistance, especially in obese type 2 diabetes patients.     

Reduced antiplatelet effect of aspirin during 24 hours in patients with coronary artery disease and type 2 diabetes

Reduced antiplatelet effect of aspirin has been reported in patients with type 2 diabetes, and recent studies suggest that once-daily aspirin provides insufficient platelet inhibition. We investigated if the effect of aspirin declined during the 24-hour dosing interval in patients with coronary artery disease and type 2 diabetes, and whether this correlated with increased platelet turnover. Furthermore, the intra-individual variation in platelet aggregation was determined during a 28-day period. We included 47 patients with coronary artery disease and type 2 diabetes treated with aspirin 75?mg daily. Blood samples were obtained 1 and 24 hours after aspirin intake, and this was repeated three times with a 2-week interval between each visit. Platelet aggregation was evaluated by impedance aggregometry (Multiplate® Analyzer) using arachidonic acid (1.0?mM) and collagen (3.2?µg/ml) as agonists. Markers of platelet turnover were measured by flow cytometry. Compliance was confirmed by serum thromboxane B₂. Platelet aggregation levels measured 1 and 24 hours after aspirin intake were compared using the mean of 1- and 24-hour measurements at the three study visits. The difference in platelet aggregation was 70?±?97?AU?×?min (p?<?0.0001) when using arachidonic acid as agonist and 33?±?76?AU?×?min (p?=?0.01) when using collagen. Markers of platelet turnover correlated positively, though not significantly, with residual platelet aggregation 24 hours after aspirin intake (p values 0.06 and 0.07). Median intra-individual variation of platelet aggregation was 9–16%. Patients with coronary artery disease and type 2 diabetes had increased platelet aggregation at the end of the 24-hour aspirin dosing interval. Platelet turnover did not correlate significantly with residual platelet aggregation, although a trend was observed. The intra-individual variation of platelet aggregation after aspirin intake was low.     

Aspirin and clopidogrel resistance: an emerging clinical entity.

Antiplatelet therapy is a cornerstone of cardiovascular medicine. Aspirin and clopidogrel have emerged as critical therapies in the treatment of cardiovascular disease. Despite their efficacy, patients on these medications continue to suffer complications. Millions of patients are currently on low-dose antiplatelet therapy but it is unknown how many of these patients are under-treated or on the wrong medication. Aspirin and clopidogrel resistance are emerging clinical entities with potentially severe consequences such as recurrent myocardial infarction, stroke, or death. The mechanism of resistance remains incompletely defined, but there are specific clinical, cellular, and genetic factors that influence therapeutic failure. These factors range from physicians who fail to prescribe these medications despite appropriate indications to polymorphisms of platelet membrane glycoproteins. Rapid and accurate diagnosis of antiplatelet resistance also remains an issue as new bedside tests are developed. By understanding the mechanism of therapeutic failure and by improving the diagnosis of this clinical entity, a new era of individualized antiplatelet therapy may arise with routine measurements of platelet activity in the same way that cholesterol, blood pressure, and blood sugar are followed, thus improving the care for millions of people.     

Response to aspirin and clopidogrel in patients scheduled to undergo cardiovascular surgery

Background Recent data indicate that among patients undergoing percutaneous coronary intervention low platelet response to aspirin is associated with clopidogrel low response. It is unclear whether these findings extend to other patient populations. We, therefore, aimed to evaluate the relation between response to aspirin and clopidogrel among patients scheduled to undergo cardiac or vascular surgery. Methods Patients who were scheduled for cardiac or vascular surgery and had taken aspirin 81–325 mg daily for at least a week and clopidogrel 75 mg daily for at least 3 days underwent blood testing for platelet function. One hundred patients were included in the current analysis. Platelet function was evaluated by the modified TEG platelet mapping assay with addition of ADP or arachidonic acid (AA), and by the PFA-100 assay with collagen-epinephrine (CEPI) or collagen-ADP (CADP) cartridges. Low response to aspirin or clopidogrel was defined as inhibition ≤20% for TEG-AA or TEG-ADP, respectively. Results Thirteen patients (13%) were low responders to aspirin and 34 (34%) were low responders to clopidogrel. Eight patients were low responders to both drugs. There were no differences in clinical characteristics between drug low responders versus sensitive patients. Aspirin low responders had lower TEG-ADP inhibition (19.5 ± 6 vs. 35.8 ± 3%, P = 0.03) and tended to have lower PFA-CADP time (84.7 ± 7 vs. 105.6 ± 5 s, P = 0.1) than aspirin sensitive patients. Clopidogrel low responders had lower TEG-AA inhibition (58 ± 6 vs. 75.1 ± 4%, P = 0.01) and PFA-CEPI time (168 ± 13 vs. 200.4 ± 10 s, P = 0.07) than clopidogrel sensitive patients. Conclusions In patients scheduled to undergo cardiovascular surgery low response to aspirin is associated with low response to clopidogrel.