阿司匹林与心脑血管疾病一级预防:2011新进展

充分的循证医学证据证实阿司匹林在心脑血管疾病的一级预防、二级预防及急性期治疗中有明确的疗效,从而使得阿司匹林成为心脑血管疾病防治的基础用药。因证据充分,阿司匹林是目前惟一被指南推荐用于一级预防的抗血小板药物。在过去的     

从指南到临床:谈阿司匹林在心脑血管疾病一级预防中的应用

心脑血管疾病是全球性的健康问题,位居全球死亡原因之首。因其高发病率、高患病率、高病死率、高致残率以及高复发率,给社会和家庭带来沉重的负担。一级预防是减少心脑血管疾病发病和减轻其疾病负担的关键。阿司匹林是目前循证医学证据     

小剂量阿司匹林在2180例高血压病患者心脑血管事件一级预防中的作用

目的探讨小剂量阿司匹林缓释片对高血压患者心脑血管事件一级预防的作用。方法由湖南省心脑血管病防治网络协作组组织其网络内的13家三甲和二甲医院参与完成前瞻性随机对照研究。2274例高血压患者被随机分为试验组和对照组,其中试验组1186例,在血压控制正常后给予肠溶阿司匹林缓释片50~100mg/d及常规降压治疗;对照组1088例,只给予常规降压治疗,观察两组患者心脑血管事件的发生情况。平均随访3.2年,最后2180例完成试验,其中试验组1151例,对照组1029例。结果试验组各事件的累积发病率为总事件3.6%、脑梗死2.1%、脑出血0.7%、心肌梗死0.2%、总死亡0.4%、因事件死亡0.2%,对照组分别为总事件5.2%、脑梗死3.6%、脑出血1.3%、心肌梗死0.9%、总死亡0.4%、因事件死亡0.3%。试验组和对照组相比,心肌梗死发病率降低,其相对危险度为0.204(95%可信区间为0.044~0.943),具有统计学差异(P<0.05)。而两组的心脑血管事件总发生率及脑梗死、脑出血、因事件死亡等终点事件比较没有统计学差异(P>0.05)。与对照组比,试验组发生心脑血管事件的相对危险度为0.701(95%可信区间为0.469~1.048),发生脑梗死的相对危险度为0.815(95%可信区间为0.470~1.412),发生脑出血的相对危险度为0.567(95%可信区间为0.235~1.368),因心脑血管事件死亡的相对危险度为3.645(95%可信区间为0.407~32.614),差异无统计学意义(P>0.05)。结论高血压患者常规降压治疗的同时加用小剂量阿司匹林缓释片可以显著降低心肌梗死的发生率,且未见增加脑出血的风险,可以起到一级预防的作用。     

心脑血管疾病的一级预防

心脑血管疾病被列为人类健康的大敌,是导致中老年人群死亡的最重要原因之一。据专家预测,21世纪我国可能出现心脑血管疾病大流行。因此积极开展一级预防刻不容缓。业已证明：以健康生活方式为主要内容的一级预防可使心脑血管疾病发病率明显下降,从而医疗费用也大幅度下降,所带来的社会和经济效益、直接和间接效益也将是无可估量的。本文采用“健康四大基石”为主的生活方式讲述其也心脑血管疾病的关系,阐述一级预防的科学性、可行性和重要性。     

阿司匹林用于糖尿病患者心血管疾病的一级预防:风险与获益?

心血管疾病(CVD)是糖尿病患者致死、致残的主要原因。现已明确,阿司匹林在降低CVD发病率和病死率方面具有益处,可作为糖尿病患者的二级预防。其在一级预防中应用的循证证据目前尚不充分,仍存在诸多争议。随着2018年ASPREE、ARRIVE和ASCEND等研究成果的公布,进一步为评价阿司匹林在糖尿病一级预防中的效益提供更多可靠的循证医学证据。本文将结合最新临床研究,分析阿司匹林在糖尿病患者CVD一级预防中的应用,就其风险与获益进行综述。     

中国2型糖尿病患者使用阿司匹林预防心脑血管事件的调查研究(CCMR-3B研究)

目的了解中国T2DM患者阿司匹林的使用情况。方法选取2010年8月至2011年3月在全国6个不同地区、104家不同级别医院就诊的T2DM患者25454例,根据既往病史将研究对象分为心脑血管事件一级预防组(n=19757)和二级预防组(n=5697)。按照中华医学会糖尿病学分会《中国2型糖尿病防治指南(2010版)》的推荐,计算各人群中阿司匹林的实际使用率。结果整体人群的阿司匹林使用率为18.78%。其中,推荐采用心脑血管事件一级预防人群的阿司匹林使用率为13.87%,需医师临床判断是否采用一级预防人群的阿司匹林使用率为11.19%;不推荐采用一级预防人群的阿司匹林使用率为6.43%。有心脑血管病史的二级预防人群的阿司匹林使用率为39.72%。结论阿司匹林在中国T2DM患者预防心脑血管事件中整体使用率偏低。     

阿司匹林在糖尿病患者心血管疾病一级预防中的应用

随着社会经济的高速发展和工业化进程的加速,糖尿病和冠心病等慢性非传染性疾病已成为世界性公共卫生问题。糖尿病与心血管疾病“如影随形”的密切联系也越来越被医师和患者所重视。阿司匹林作为预防心脑血管事件发生的经典药物,是否可以同样有效预防糖尿病患者的心血管事件并带来远期获益？本文回顾新近临床研究和荟萃分析结果,并结合我国国情探讨阿司匹林对糖尿病患者心血管事件预防的作用。     

《ADA／AHA／ACCF阿司匹林用于糖尿病人群心血管事件一级预防》指南解读（一）

动脉粥样硬化性心脑血管疾病是导致糖尿病患者致残和致死的主要原因,主要与糖尿病患者存在的血管内皮受损、血小板过度激活及动脉内血栓形成密切相关,因此,心血管疾病的预防是糖尿病治疗方案中重要的组成部分。众所周知,阿司匹林在心血管疾病二级预防中的疗效已经被大量的研究证据所证实,而对于心血管疾病的一级预防,目前的共识是限于那些10年心血管病风险在10％以上的人群。     

阿司匹林对心脑血管疾病的预防

阿司匹林在心脑血管疾病的一级和二级预防中均显示出卓越的作用,它可以降低心肌梗死、卒中的发病及死亡的风险.一级预防是指对没有发生心脑血管疾病的人群采取措施,防止首次事件的发生;二级预防是指对已经发生了心脑血管疾病的患者采取防治措施,目的 是降低病死病残率,同时防止心肌梗死、卒中等事件的复发.阿司匹椿为心脑血管疾病的预防提供了一个强有力的工具,为医生提供了一个很好的治疗平台,普及阿司匹林知识对中国以预防为主理念的贯彻执行有重要意义.阿司匹林是效益风险比和效益费用比最高的药物之一,对于我国这一中低收入且人口众多的国家,这类事半功倍、经济有效的预防方法显得更有实际意义.     

阿司匹林一级预防的研究进展

阿司匹林通过抑制环氧化酶阻断血栓烷A2生成而发挥抗血小板聚集作用。已有临床证据证明阿司匹林可减少冠状动脉急性事件发生,起到心血管疾病一级预防作用。阿司匹林的心血管疾病二级预防地位已得到肯定,一级预防作用尚存在争议。现对近期有关阿司匹林在一级预防的试验和进展进行综述,以期为临床阿司匹林应用提供参考。     

中国四省市阿司匹林预防心血管疾病用药现状调查

目的 调查阿司匹林在我国部分地区心血管疾病一级预防和二级预防中的应用现状.方法 入选来自2007年6月至2008年5月糖尿病和代谢综合征患病率变迁调查研究中湖南、广东、四川、辽宁四省的9000例受试者,进行问卷调查,内容包括是否服用阿司匹林、服用频率及剂量.总体人群心血管一级预防治疗标准依据美国心脏病协会心血管及脑卒中一级预防指南（2002）10年心血管风险＞10%的推荐,计算阿司匹林实际使用率;糖尿病和高血压亚组则分别将美国糖尿病协会（2010）指南和欧洲心脏病学会/欧洲高血压协会高血压指南（2007）的相关推荐作为治疗标准.结果 共收回7186份有效问卷,其中233例有明确的心血管疾病.总人群中符合一级预防人群实际阿司匹林使用率为14.09%,二级预防人群使用率为26.61%;糖尿病亚组无心血管疾病患者实际阿司匹林使用率为32.47%,糖尿病心血管疾病二级预防阿司匹林使用率为51.16%.高血压亚组心血管疾病一级预防阿司匹林使用率为19.93%,二级预防人群使用率为29.52%.所有服用阿司匹林的人群中,87.67%为每日1次,10.35%为不规律服用,1.98%为隔日1次,半数受试者（50.25%）服用剂量低于指南推荐的最小剂量.结论 我国心血管疾病一级预防和二级预防人群阿司匹林使用率过低,在使用阿司匹林预防的人群中,使用剂量也不规范,半数每日应用少于75 mg.应进一步提高心血管疾病中高危患者及已有心血管疾病患者阿司匹林的使用率并规范其应用.     

Effect of aspirin on mortality in the primary prevention of cardiovascular disease

Objective

The lack of a mortality benefit of aspirin in prior meta-analyses of primary prevention trials of cardiovascular disease has contributed to uncertainty about the balance of benefits and risks of aspirin in primary prevention. We performed an updated meta-analysis of randomized controlled trials of aspirin to obtain best estimates of the effect of aspirin on mortality in primary prevention.

Methods

Eligible articles were identified by searches of electronic databases and reference lists. Outcomes of interest were all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and bleeding. Data were pooled from individual trials using the DerSimonian-Laird random-effects model, and results are presented as relative risk (RR) and 95% confidence intervals (CIs).

Results

Nine randomized controlled trials enrolling 100,076 participants were included. Aspirin reduced all-cause mortality (RR 0.94; 95% CI, 0.88-1.00), myocardial infarction (RR 0.83; 95% CI, 0.69-1.00), ischemic stroke (RR 0.86; 95% CI, 0.75-0.98), and the composite of myocardial infarction, stroke, or cardiovascular death (RR 0.88; 95% CI, 0.83-0.94), but did not reduce cardiovascular mortality (RR 0.96; 95% CI, 0.84-1.09). Aspirin increased the risk of hemorrhagic stroke (RR 1.36; 95% CI, 1.01-1.82), major bleeding (RR 1.66; 95% CI, 1.41-1.95), and gastrointestinal bleeding (RR 1.37; 95% CI, 1.15-1.62). A lack of availability of patient-level data precluded exploration of benefits and risks of aspirin in key subgroups.

Conclusion

Aspirin prevents deaths, myocardial infarction, and ischemic stroke, and increases hemorrhagic stroke and major bleeding when used in the primary prevention of cardiovascular disease.     

AHA/ADA vs. ESC/EASD recommendations on aspirin as a primary prevention strategy in people with diabetes: how the same data generate divergent conclusions.

Recently, major scientific societies in Europe and USA have issued guidelines on diabetes and cardiovascular (CV) disease. The conclusions of the two panels of experts regarding the use of aspirin for the primary prevention of CV disease in individuals with diabetes are totally divergent. The US statement recommends the use of aspirin for primary prevention in all individuals aged > 40 or with additional risk factors. In contrast, in the European guidelines there is no mention of aspirin for the primary prevention of myocardial infarction or CV death, while it is recommended for the prevention of stroke. Both recommendations seem mainly based on extrapolations from data on other high-risk groups, rather than on a comprehensive review of pertinent data. Actually, a body of evidence suggests that the efficacy of aspirin in patients with diabetes is substantially lower than in individuals without diabetes. Nevertheless, existing knowledge is mainly derived from dated trials, including small numbers of patients, and hardly representing current strategies for the management of CV risk factors. The high level of uncertainty regarding the balance between benefits and risks of aspirin therapy have important implications for clinical practice, auditing activities, and the design and conduct of randomized clinical trials.     

小剂量阿司匹林对心血管病一级预防效果及安全性的系统评价

目的 系统评价小剂量阿司匹林在高危人群中一级预防心血管病的有效性和安全性.方法 计算机检索MEDLINE、EMbase、Cochrane图书馆(2008年第3期)、中国生物医学文献数据库、中国学术期刊全文数据库,同时筛检了纳入文献的参考文献.收集小剂量阿司匹林(75～150 mg)一级预防心血管病的随机对照试验(RCT),2名评价员独立评价文献质量和提取资料,并采用RevMan4.2软件对资料进行荟萃分析.结果 共纳入6个研究(TPT,HOT,PPP,WHS,POPADAD,JPAD),72 466例患者.(1)小剂量阿司匹林总的心血管事件的发生率(RR=0.85,95% CI:0.80～0.92)、卒中发生率(RR=0.87,95% CI:0.77～0.98)、非致死性卒中发生率(RR=0.81,95%CI:0.70～0.95)、短暂脑缺血发作发生率(RR=0.76,95%CI:0.64～0.90)均低于安慰剂(均P＜0.05).(2)小剂量阿司匹林非致死性心肌梗死(RR=0.89,95%CI:0.77～1.02)、心血管性死亡(RR=0.98,95% CI:0.86～1.13)、全因死亡发生率(RR=0.95,95%CI:0.88～1.02)与安慰剂比较,差异无统计学意义(P＞0.05).(3)在老年人群中分析显示,小剂量阿司匹林冠心病的发生率低于安慰剂(RR=0.81,95%CI:0.70～0.94,P＜0.01).(4)在安全性方面,与安慰剂比较,小剂量阿司匹林有出血并发症的风险(RR=1.15,95%CI:1.12～1.18,P＜0.01),而在过敏反应方面差异无统计学意义(P＞0.05).结论 小剂最阿司匹林能降低总的心血管事件、短暂脑缺血发作、卒中、非致死性卒中的发生率;对降低非致死性心肌梗死、心血管性死亡、全因死亡方面效果不明显;在老年人群中小剂量阿司匹林能降低冠心病的发牛率;长期应用无明显过敏反应,但存在出血并发症的风险.     

Low-doses aspirin in the primary prevention of cardiovascular disease in patients with diabetes: Meta-analysis stratified by baseline cardiovascular risk

Background and aimThe aim of this meta-analysis was to analyze the risks and benefits of low-dose aspirin in patients with T2D without cardiovascular conditions according to the baseline cardiovascular risk.MethodsWe performed a meta-analysis including randomized clinical trials that evaluated the use of low-dose aspirin (75–100 mg/day) versus placebo/usual care in patients with T2D. Studies were classified as low, moderate and high risk based on the number of events in the placebo/control arms or by cardiovascular risk score when reported. The incidence of MACE, cardiovascular mortality and bleeding were evaluated.ResultsTen eligible trials (34069 patients) were considered eligible for the analyses. According to the stratified analysis, low-dose aspirin use was associated with reduced risk for MACE in the moderate/high-risk group (OR: 0.88; 95% CI, 0.80–0.97; I² = 0%) but not in the low-risk group (OR: 0.89; 95% CI, 0.77–1.01; I² = 0%). Likewise, low-dose aspirin use was associated with more bleeding in the low-risk group, showing a non-significant trend in the moderate/high-risk group. There was no reduction in cardiovascular mortality in either group. Beyond the different findings in each stratum, the differences between the subgroups were not statistically significant.ConclusionThis study showed that low-dose aspirin in patients with T2D reduces MACE and increases bleeding. Based on the within-subgroups results, the baseline cardiovascular risk does not modify the effect of aspirin therapy. However, few studies were included and the comparison between subgroups showed a trend in favor to the highest risk group, these results should be confirmed in future studies.     

Primary and secondary prevention strategy for cardiovascular disease in diabetes mellitus

The majority of individuals with diabetes die from cardiovascular disease (CVD) and related complications. The risk of CVD is 2 to 4 fold greater in diabetes and largely magnified by co-morbidities that aggregate along with it. Sufficient evidence-based data now exist to support multifactorial risk intervention with specific targets for goal-directed therapy for both primary and secondary prevention. These interventions have shown survival benefit in addition to prevention of vascular complications. Prevention of diabetes and delaying its onset should also be an important aspect in future health care strategy and research to confront the oncoming tsunami of CVD related to diabetes.     

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.     

2型糖尿病对阿司匹林和氯吡格雷双联抗血小板药物治疗效应的分析

目的:本研究通过前瞻性连续入选在我院因稳定性冠心病行经皮冠状动脉介入治疗(PCI)的患者,分析探讨糖尿病对阿司匹林和氯吡格雷双联抗血小板药物效应的影响。方法:2008年8月至2011年11月前瞻性连续入选稳定性冠心病患者。入院后服用氯吡格雷前测定花生四烯酸(AA)诱导的血小板聚集率和基线二磷酸腺苷(ADP)诱导的血小板聚集率,之后给予氯吡格雷300 mg负荷量口服,继续服用氯吡格雷75 mg/d至1 d后,再次测定服用氯吡格雷后ADP诱导的血小板聚集率。结果:入选了355例稳定性冠心病患者,其中合并2型糖尿病103例,非糖尿病252例。阿司匹林抵抗的发生率18.6%,糖尿病组与非糖尿病组阿司匹林抵抗的发生率未见明显差异(20.4%vs.17.9%,P=0.578),将患者基线特征纳入Logistic回归模型进行校正后结果显示,糖尿病并未增高阿司匹林抵抗的风险(OR=1.3,95%CI=0.7～2.7,P=0.439)。氯吡格雷抵抗的发生率为20.8%;糖尿病组氯吡格雷抵抗的发生率明显高于非糖尿病组(33.0%vs.15.9%,P<0.001);Logistic回归校正后结果显示,糖尿病是氯吡格雷抵抗的独立危险因素(OR=5.7,95%CI=2.9～11.1,P<0.001)。结论:双联抗血小板药物基础上,糖尿病未增高阿司匹林抵抗的风险;但是糖尿病明显增高了氯吡格雷抵抗的风险。     

Meta-analysis of multiple primary prevention trials of cardiovascular events using aspirin

Several meta-analyses have focused on determination of the effectiveness of aspirin (acetylsalicylic acid) in primary prevention of cardiovascular (CV) events. Despite these data, the role of aspirin in primary prevention continues to be investigated. Nine randomized trials have evaluated the benefits of aspirin for the primary prevention of CV events: the British Doctors' Trial (BMD), the Physicians' Health Study (PHS), the Thrombosis Prevention Trial (TPT), the Hypertension Optimal Treatment (HOT) study, the Primary Prevention Project (PPP), the Women's Health Study (WHS), the Aspirin for Asymptomatic Atherosclerosis Trial (AAAT), the Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial, and the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial. The combined sample consists of about 90,000 subjects divided approximately evenly between those taking aspirin and subjects not taking aspirin or taking placebo. A meta-analysis of these 9 trials assessed 6 CV end points: total coronary heart disease, nonfatal myocardial infarction (MI), total CV events, stroke, CV mortality, and all-cause mortality. No covariate adjustment was performed, and appropriate tests for treatment effect, heterogeneity, and study size bias were applied. The meta-analysis suggested superiority of aspirin for total CV events and nonfatal MI, (p <0.05 for each), with nonsignificant results for decreased risk for stroke, CV mortality, and all-cause mortality. There was no evidence of a statistical bias (p >0.05). In conclusion, aspirin decreased the risk for CV events and nonfatal MI in this large sample. Thus, primary prevention with aspirin decreased the risk for total CV events and nonfatal MI, but there were no significant differences in the incidences of stroke, CV mortality, all-cause mortality and total coronary heart disease.