Aspirin in the treatment and prevention of cardiovascular disease: Current perspectives and future directions

In secondary prevention among male and female survivors of prior myocardial infarction (MI), occlusive stroke, transient ischemic attack, and other high-risk conditions, long-term use of aspirin confers very similar statistically significant and clinically important reductions in MI, stroke, and cardiovascular death. In men and women suffering acute MI or acute occlusive stroke, aspirin confers similar benefits. In primary prevention, aspirin confers a statistically significant and clinically important reduction in risk of a first MI, but the data on stroke and cardiovascular disease death remain inconclusive, so aspirin should be prescribed on an individual basis by the healthcare provider who weighs this clear benefit against long-term side effects. Worldwide, aspirin used more widely and appropriately would avoid many premature deaths in secondary prevention, during acute MI, and during acute stroke, as well as many first MI in primary prevention.     

Antiplatelet therapy in the treatment of atherothrombotic disease: considering the evidence

Aspirin should be used to treat patients with acute myocardial infarction (MI) and continued indefinitely to reduce vascular death, nonfatal MI, and nonfatal stroke. Clopidogrel added to aspirin is beneficial in the treatment of patients with acute ST-elevation MI. Patients with unstable angina or non-ST-elevation MI should be treated with aspirin plus clopidogrel for at least 9 months to reduce the risk vascular death, nonfatal MI, and nonfatal stroke. Patients with prior MI should be treated indefinitely with aspirin and with clopidogrel if aspirin is contraindicated. Patients with ischemic stroke should be treated with either aspirin or clopidogrel indefinitely. Extended-release dipyridamole plus low-dose aspirin is more efficacious than low-dose aspirin but is associated with an insignificant increase in nonfatal MI and vascular death than low-dose aspirin. Clopidogrel is more effective than aspirin in reducing the risk of vascular death, nonfatal MI, and nonfatal stroke in patients with peripheral arterial disease.     

Prevention of cardiovascular disease

Aspirin has been tested for its benefit in preventing cardiovascular disease in randomized trials in three categories of patients. In secondary prevention among those with a history of myocardial infarction (MI), stroke or transient cerebral ischemia, or unstable angina pectoris, 25 randomized trials demonstrated significant reductions from aspirin of 25% for the occurrence of an “important vascular event” (nonfatal MI, nonfatal stroke, or vascular death), 32% for nonfatal MI, 27% for nonfatal stroke, and 15% for vascular mortality. Among those evolving an MI, the Second International Study of Infarct Survival (ISIS-2) showed a significant reduction of 23% in five-week vascular mortality among those started on a one-month regimen of daily aspirin within 24 hours of the onset of symptoms of suspected MI. Aspirin also significantly reduced reinfarction, nonfatal stroke, and important vascular events. Finally, in primary prevention, the US Physicians’ Health Study (PHS) showed a significant 44% reduction in the occurrence of a first MI among apparently healthy male physicians; numbers of strokes and vascular deaths were insufficient to permit conclusions for these endpoints. Thus, aspirin is of clear benefit in reducing MI, stroke, and vascular death in secondary prevention and among those evolving an MI. It is also beneficial in the primary prevention of MI among men over 40, but data concerning its effects on stroke and vascular death remain inconclusive.     

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.     

Meta-analysis of data from the six primary prevention trials of cardiovascular events using aspirin

Until recently, 5 major studies have formed the basis for the use of aspirin (acetylsalicylic acid) in primary prevention of cardiovascular (CV) events. Despite these data, the role of aspirin in primary prevention has not been established firmly. Six randomized trials have evaluated the benefits of aspirin for the primary prevention of CV events: the British Doctors' Trial, the Physicians' Health Study, the Thrombosis Prevention Trial, the Hypertension Optimal Treatment study, the Primary Prevention Project, and the Women's Health Study. The combined sample consists of 47,293 subjects on aspirin and 45,580 not on aspirin or placebo. A meta-analysis of these 6 trials assessed 6 CV end points: total coronary heart disease (CHD), 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. Using odds ratios and confidence intervals, the meta-analysis suggested superiority of aspirin for total CHD, nonfatal MI, and total CV events (p < or =0.001 in each case), with a nonsignificant trend (0.07 < p <0.34) for decreased risk of stroke, CV mortality, and all-cause mortality. There was no evidence of statistical bias (p >0.05). Given the study size and cohort, aspirin decreased the risk of CV events in this large patient sample. In conclusion, primary prevention with aspirin decreased the risk of total CHD, nonfatal MI, and total CV events, but there were no significant differences in the incidences of stroke or CV mortality.     

Aspirin in the primary prevention of cardiovascular disease: Current knowledge and future research needs

In secondary prevention, among a very wide range of survivors of prior occlusive cardiovascular disease (CVD) events and those suffering acute myocardial infarction (MI) or occlusive stroke, aspirin decreases risks of MI, stroke, and CVD death. In these high risk patients, the absolute benefits are large and absolute risks are far smaller so aspirin should be more widely prescribed. In contrast, in primary prevention, aspirin reduces risks of first MI but the evidence on stroke and CVD death remain inconclusive. Based on the current totality of evidence from predominantly low risk subjects where the absolute benefits is low and side effects the same as in secondary prevention, any decision to prescribe aspirin for primary prevention should be an individual clinical judgment by the healthcare provider that weighs the absolute benefit in reducing the risk of a first MI against the absolute risk of major bleeding. If the ongoing trials of intermediate risks subjects show net benefits then general guidelines may be justified with several caveats. First, any decision to use aspirin should continue to be made by the healthcare provider. Second, therapeutic lifestyle changes and other drugs of life saving benefit such as statins should be considered with aspirin as an adjunct, not alternative. The more widespread and appropriate use of aspirin in primary prevention is particularly attractive, especially in developing countries where CVD is emerging as the leading cause of death. In addition, aspirin is generally widely available over the counter and is extremely inexpensive.     

Use of antiplatelet drugs in secondary prevention in older persons with atherothrombotic disease

Unless there are contraindications to the use of aspirin, aspirin should be used in treating patients with acute myocardial infarction (MI) and continued indefinitely to reduce vascular death, nonfatal MI, and nonfatal stroke. Clopidogrel added to aspirin has been shown to be beneficial in the treatment of patients with acute ST-elevation MI. Patients with unstable angina or non-ST-elevation MI should be treated with aspirin plus clopidogrel for at least 9 months to reduce vascular death, nonfatal MI, and nonfatal stroke. Patients with prior MI should be treated indefinitely with aspirin and with clopidogrel if aspirin is contraindicated. Patients with ischemic stroke should be treated with either aspirin or clopidogrel indefinitely. Extended release dipyridamole plus low dose aspirin has been shown to be more efficacious than low dose aspirin in only one large study, and is associated with an insignificant increase in nonfatal MI and vascular death over low dose aspirin alone. Clopidogrel is significantly more effective than aspirin in reducing vascular death, nonfatal MI, and nonfatal stroke in patients with peripheral arterial disease.     

Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis

Objective

Many recommendations for aspirin in stable cardiovascular disease are based on analyses of all antiplatelet therapies at all dosages and in both stable and unstable patients. Our objective was to evaluate the benefit and risk of low-dose aspirin (50-325 mg/d) in patients with stable cardiovascular disease.

Methods

Secondary prevention trials of low-dose aspirin in patients with stable cardiovascular disease were identified by searches of the MEDLINE database from 1966 to 2006. Six randomized trials were identified that enrolled patients with a prior myocardial infarction (MI) (n = 1), stable angina (n = 1), or stroke/transient ischemic attack (n = 4). A random effects model was used to combine results from individual trials.

Results

Six studies randomized 9853 patients. Aspirin therapy was associated with a significant 21% reduction in the risk of cardiovascular events (nonfatal MI, nonfatal stroke, and cardiovascular death) (95% confidence interval [CI], 0.72-0.88), 26% reduction in the risk of nonfatal MI (95% CI, 0.60-0.91), 25% reduction in the risk of stroke (95% CI, 0.65-0.87), and 13% reduction in the risk of all-cause mortality (95% CI, 0.76-0.98). Patients treated with aspirin were significantly more likely to experience severe bleeding (odds ratio 2.2, 95% CI, 1.4-3.4). Treatment of 1000 patients for an average of 33 months would prevent 33 cardiovascular events, 12 nonfatal MIs, 25 nonfatal strokes, and 14 deaths, and cause 9 major bleeding events. Among those with ischemic heart disease, aspirin was most effective at reducing the risk of nonfatal MI and all-cause mortality; however, among those with cerebrovascular disease, aspirin was most effective at reducing the risk of stroke.

Conclusion

In patients with stable cardiovascular disease, low-dose aspirin therapy reduces the incidence of adverse cardiovascular events and all-cause mortality, and increases the risk of severe bleeding.     

Aspirin for Primary Prevention of Cardiovascular Events

BackgroundThe efficacy and safety of aspirin for primary prevention of cardiovascular disease (CVD) remain debatable.ObjectivesThe purpose of this study was to examine the clinical outcomes with aspirin for primary prevention of CVD after the recent publication of large trials adding >45,000 individuals to the published data.MethodsRandomized controlled trials comparing clinical outcomes with aspirin versus control for primary prevention with follow-up duration of ≥1 year were included. Efficacy outcomes included all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, transient ischemic attack (TIA), and major adverse cardiovascular events. Safety outcomes included major bleeding, intracranial bleeding, fatal bleeding, and major gastrointestinal (GI) bleeding. Random effects DerSimonian-Laird risk ratios (RRs) for outcomes were calculated.ResultsA total of 15 randomized controlled trials including 165,502 participants (aspirin n = 83,529, control n = 81,973) were available for analysis. Compared with control, aspirin was associated with similar all-cause death (RR: 0.97; 95% confidence interval [CI]: 0.93 to 1.01), CV death (RR: 0.93; 95% CI: 0.86 to 1.00), and non-CV death (RR: 0.98; 95% CI: 0.92 to 1.05), but a lower risk of nonfatal MI (RR: 0.82; 95% CI: 0.72 to 0.94), TIA (RR: 0.79; 95% CI: 0.71 to 0.89), and ischemic stroke (RR: 0.87; 95% CI: 0.79 to 0.95). Aspirin was associated with a higher risk of major bleeding (RR: 1.5; 95% CI: 1.33 to 1.69), intracranial bleeding (RR: 1.32; 95% CI: 1.12 to 1.55), and major GI bleeding (RR: 1.52; 95% CI: 1.34 to 1.73), with similar rates of fatal bleeding (RR: 1.09; 95% CI: 0.78 to 1.55) compared with the control subjects. Total cancer and cancer-related deaths were similar in both groups within the follow-up period of the study.ConclusionsAspirin for primary prevention reduces nonfatal ischemic events but significantly increases nonfatal bleeding events.     

Antiplatelet therapy in the treatment of cerebrovascular disease

Aspirin and the new agent ticlopidine have been the most thoroughly evaluated of the platelet-antiaggregating drugs used for the prevention of stroke and other vascular events. Numerous trials have shown aspirin to be effective in reducing the risk of myocardial infarction (MI), recurrent transient ischemic attacks, stroke, and vascular death in men at high risk for these events. Primary prevention trials have shown that aspirin reduces the risk of MI in healthy men over 50 years of age but does not reduce the risk of stroke. Two large, multicenter trials have shown that ticlopidine is effective in reducing the risk of fatal and nonfatal stroke in both men and women. Ticlopidine may also be effective in reducing the risk of recurrent stroke in patients who have had a completed thromboembolic stroke.     

Aspirin to prevent heart attack and stroke: what's the right dose?

Despite hundreds of clinical trials, the appropriate dose of aspirin to prevent myocardial infarction (MI) and stroke is uncertain. In the US, the doses most frequently recommended are 80, 160, or 325 mg per day. Because aspirin can cause major bleeding, the appropriate dose is the lowest dose that is effective in preventing both MI and stroke because these two diseases frequently co-exist. Five randomized clinical trials have compared aspirin with placebo or no therapy for the prevention of stroke and MI. These trials varied with regard to the dose of aspirin, the duration of treatment, and, most important, the populations selected for study varied in their baseline risk of stroke and MI. In men, 160 mg/day consistently lowered the risk of MI. In women, doses of 50 mg, 75, and 100 mg/day did not significantly decrease the risk of MI; therefore, the appropriate dose in women must exceed 100 mg/day. The appropriate dose for the primary prevention of stroke in men and women has not been established. Doses of 75 and 100 mg/day have been ineffective in men and women. The appropriate dose must be at least 160 mg/day. The lowest dose to prevent recurrent MI or death in patients with stable coronary artery disease (CAD) is 75 mg/day. In acute MI the lowest dose is 160 mg/day. In patients with a history of stroke or transient ischemic attack (TIA), 50 mg/day has been shown to be effective in men and women. In acute stroke, 160 mg/day is effective in preventing recurrent stroke or death. The risk of major bleeding with 160 mg/day is the same as with 80 mg/day: 1 to 2 cases per 1000 patient years of treatment, and the risk of fatal bleeding is the same with 80 and 160 mg/day. These studies indicate that the most appropriate dose for the primary and secondary prevention of stroke and MI is 160 mg/day.     

Low-dose aspirin for primary prevention of cardiovascular disease

Progressive atherosclerosis followed by plaque rupture is the leading cause of acute cardiovascular events. Inhibition of platelet aggregation by acetylsalicylic acid (aspirin) reduces recurrent cardiovascular events in secondary prevention trials. By extracting data from available randomized trials that examined aspirin prevention in persons without previously known cardiovascular disease, we evaluated the use of aspirin as a primary prevention measure. Using the raw data presented in the source publication on death, fatal and nonfatal myocardial infarctions, and cerebrovascular accidents, all relative and absolute risk reductions were recalculated with confidence intervals. In healthy men above 45 years of age, men with an increased cardiovascular risk profile, and persons with diabetes mellitus or hypertension, the use of aspirin reduces the incidence of myocardial infarction and has a neutral effect on cerebrovascular events. The protective effect of aspirin is apparently most prominent in those persons with an increased risk of manifest atherosclerotic vascular disease. Notwithstanding these results, for each patient it remains essential to balance the cardiovascular risk profile against the small increased risk of bleeding complications when prescribing aspirin.     

Platelet inhibitors and antioxidant vitamins in cardiovascular disease

Considerable research attention has focused on the possible roles of platelet inhibition, principally using aspirin, and antioxidant vitamins in reducing the risks of cardiovascular disease. Data from large-scale randomized trials indicate that aspirin reduces subsequent vascular events among patients with prior myocardial infarction, stroke, transient ischemic attacks, or unstable angina, as well as among patients with acute evolving myocardial infarction. In primary prevention trials, the Physicians' Health Study showed a clear benefit in decreasing risk of a first myocardial infarction in men; the data on stroke and total number of deaths from vascular causes are inadequate. The Women's Health Study, a trial now under way among apparently healthy women, will provide direct evidence on the balance of risks and benefits of aspirin in primary prevention. Antioxidant vitamins are hypothesized to decrease cardiovascular disease risk by several mechanisms, including inhibition of oxidation of low-density lipoprotein cholesterol and decreasing uptake into the coronary endothelium. Promising results have emerged from observational studies, which show that people with high intakes of antioxidant vitamins through diet or supplements have lowered risks of cardiovascular disease; however, unknown or unmeasured factors associated with high antioxidant vitamin intake may explain all or part of the observed associations. Randomized trials to provide reliable data are now ongoing among apparently healthy men and women, as well as among survivors of prior cardiovascular disease events.     

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.     

An overview of the 4 randomized trials of aspirin therapy in the primary prevention of vascular disease

BACKGROUND: In the primary prevention of cardiovascular disease, in contrast to the recommendations of the American College of Chest Physicians and the American Heart Association, the US Food and Drug Administration recently stated that there was insufficient evidence to judge whether aspirin therapy decreases the risk of a first myocardial infarction. OBJECTIVE: To perform an overview of the 4 primary prevention trials of aspirin therapy to obtain the most reliable estimates of the effects of aspirin therapy on various vascular disease end points. METHODS AND RESULTS: These 4 trials included more than 51,000 subjects and 2284 important vascular events. Those assigned to aspirin therapy experienced significant reductions of 32% (95% confidence interval [CI], 21%-41%) for nonfatal myocardial infarction and 13% (95% CI, 5%-19%) for any important vascular event. There were possible small but nonsignificant increases in risks of vascular disease-related death (1%; 95% CI, -12% to 16%) and nonfatal stroke (8%; 95% CI, -12% to 33%). When strokes were subdivided by type, there was no significant effect of aspirin therapy on the risk of ischemic stroke, but, while based on small numbers, there was a 1.7-fold apparent increase (95% CI, 6%-269%) in the risk of hemorrhagic stroke, which did achieve statistical significance. CONCLUSIONS: For the primary prevention of vascular disease, aspirin therapy confers significant beneficial effects on first myocardial infarction and, as a result, on any important vascular event; these effects are clinically important. Whether there is any reduction in vascular disease-related death or stroke associated with treatment remains unclear because of inadequate numbers of events in the primary prevention trials completed to date. More data on hemorrhagic stroke are also needed. In addition, randomized trial data, especially in women but also in men, are needed to help to formulate a rational public health policy for individuals at usual risk. Meanwhile, these data provide evidence for a significant benefit of aspirin therapy in the primary prevention of myocardial infarction.     

Genomics and the efficacy of aspirin in the treatment of cerebrovascular disease

Opinion statement  Aspirin has been shown to reduce the risk of stroke, myocardial infarction, and death in patients with a history of cardiovascular disease or at high risk for cardiovascular disease. However, many individuals suffer a stroke or other cardiovascular event despite aspirin therapy. Data suggest that heritability contributes importantly to the antiplatelet and clinical responses to aspirin. Candidate genes for influencing aspirin response include those involved in platelet aggregation and in modulating cardiovascular disease risk and progression. Although several studies have examined genetic determinants of platelet responsiveness to aspirin, the results are largely inconsistent. Few studies have examined genetic association with clinical outcomes, including reductions in stroke risk, with aspirin. In perhaps the most significant pharmacogenomic study with aspirin to date, a large primary prevention trial showed that the apolipoprotein A genotype was associated with risk of stroke and other cardiovascular events in women and that aspirin eliminated this risk. These data suggest that ultimately, it may be possible to tailor aspirin therapy based on an individual’s genotype, at least for primary prevention of stroke and cardiovascular events in women. Data on genetic determinants of response to aspirin in secondary stroke prevention are far less advanced. Future pharmacogenomic studies should focus on elucidating the role of genotyping in choosing appropriate antiplatelet therapy (ie, aspirin alone versus a thienopyridine or combination antiplatelet therapy) for secondary disease prevention.     

Additive benefits of pravastatin and aspirin to decrease risks of cardiovascular disease: randomized and observational comparisons of secondary prevention trials and their meta-analyses

BACKGROUND: In randomized trials of secondary prevention, pravastatin sodium and aspirin reduce risks of cardiovascular disease. Pravastatin has a predominantly delayed antiatherogenic effect, and aspirin has an immediate antiplatelet effect, raising the possibility of additive clinical benefits. METHODS: In 5 randomized trials of secondary prevention with pravastatin (40 mg/d), comprising 73 900 patient-years of observation, aspirin use was also prescribed in varying frequencies, and data were available on a large number of confounding variables. We tested whether pravastatin and aspirin have additive benefits in the 2 large trials (Long-term Intervention With Pravastatin in Ischaemic Disease trial and the Cholesterol and Recurrent Events trial) that were designed to test clinical benefits. We also performed meta-analyses of these 2 trials and 3 smaller angiographic trials that collected clinical end points. In all analyses, multivariate models were used to adjust for a large number of cardiovascular disease risk factors. RESULTS: Individual trials and all meta-analyses demonstrated similar additive benefits of pravastatin and aspirin on cardiovascular disease. In meta-analysis, the relative risk reductions for fatal or nonfatal myocardial infarction were 31% for pravastatin plus aspirin vs aspirin alone and 26% for pravastatin plus aspirin vs pravastatin alone. For ischemic stroke, the corresponding relative risk reductions were 29% and 31%. For the composite end point of coronary heart disease death, nonfatal myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or ischemic stroke, the relative risk reductions were 24% and 13%. All relative risk reductions were statistically significant. CONCLUSION: More widespread and appropriate combined use of statins and aspirin in secondary prevention of cardiovascular disease will avoid large numbers of premature deaths.     

阿司匹林在心血管病一级预防的地位

阿司匹林作为急性心肌梗死和冠心病二级预防的基础药物已得到广泛认可,然而近年来关于阿司匹林对心血管疾病的一级预防依然存在争议。阿司匹林可降低心脑血管事件的发生率,但同时又可增加出血事件。如何将其合理地运用在心血管疾病一级预防中使更多的患者获益是临床工作者的一大难题。越来越多的大规模临床研究表明阿司匹林作为心血管疾病一级预防药物的关键在于把握危险分层,进一步评价患者的状况,规范使用阿司匹林将会有效地减少心血管疾病的风险。与此同时国外许多指南及我国专家的共识均能指导医生在心血管疾病一级预防中规范地运用阿司匹林。     

CON: Should Aspirin Be Used in All Women Older Than 65 Years to Prevent Stroke?

A goal of the Women's Health Study was to evaluate the balance of benefits and risks of low-dose aspirin in the primary prevention of stroke in healthy women. A total of 39,876 female health care professionals aged 45 years and older were randomly assigned to either low-dose aspirin (100 mg every other day) or placebo and followed for an average of 10 years. In the overall study population, aspirin significantly lowered the risk of total and ischemic stroke without affecting the risk of myocardial infarction or death from cardiovascular causes, leading to a nonsignificant finding with respect to the primary end point of total cardiovascular disease. In women aged 65 years or older, aspirin significantly reduced the risk of ischemic stroke, as well as myocardial infarction and total cardiovascular disease. While the findings suggest that aspirin should be considered for primary prevention of stroke in women aged 65 years or older, the balance of benefits and risks would not support recommending aspirin for all women in this age group. The discussion on whether to use aspirin should be had on an individual basis, assessing the net risks and benefits.     

Aspirin for primary prevention of atherosclerotic disease in Japan

Atherosclerotic disease is the most prevalent cause of death worldwide. The ratio of coronary heart disease/cerebrovascular disease differs between Japan and Western countries and the incidence of hemorrhagic stroke and gastrointestinal bleeding is higher in Japan. Thus, the threshold for aspirin administration for primary prevention has been controversial in Japan. Much anecdotal data from Western countries and from Japan has implied that the threshold for administering aspirin to those with risk factors for coronary heart disease is higher than that recommended in Western countries, and that the potential candidates for primary prevention in Japan seem to be diabetic patients. The Japanese primary Prevention of atherosclerosis with Aspirin for Diabetes (JPAD) trial involving 2,530 patients with type 2 diabetes started in December 2002. Compared to other primary prevention trials, this trial offered an acceptable sample size, a standard aspirin dosage, and gender balance. Because stroke is the most significant component of all atherosclerotic diseases in Japan, the impact of primary prevention with aspirin on stroke should be understood. Thus, the JPAD trial should generate reliable data on primary prevention with aspirin for diabetic patients that would also be relevant to other countries.