重庆第三军医大学大坪医院心内科 曾春雨、杨成明

Presentation on theme: "重庆第三军医大学大坪医院心内科 曾春雨、杨成明"— Presentation transcript:

1 重庆第三军医大学大坪医院心内科 曾春雨、杨成明
阿司匹林用于心血管病一级预防 重庆第三军医大学大坪医院心内科 曾春雨、杨成明

2 2009年 阿司匹林应用中国专家共识建议阿司匹林75～100mg/d作为以下人群的心血管疾病一级预防措施：
  

3 45～79岁男性，10年冠心病危险≥4％～12％、没有胃肠道出血的高危因素。
55～79岁女性，10年脑卒中危险≥3％～11％、没有胃肠道出血的高危因素。 糖尿病患者40岁以上，或30岁以上伴有1项其他心血管病危险因素如早发心血管病家族史、高血压、吸烟、血脂异常或白蛋白尿。 高血压但血压基本控制（＜150/90mmHg），同时有下列情况之一者：①年龄50岁以上②有靶器官损害，包括血浆肌酐中度增高③糖尿病。

4 合并下述三项及以上危险因素的患者：①血脂异常②吸烟③肥胖④50岁以上⑤早发心血管病家族史。
其他10年心脑血管疾病事件危险≥10％的中、高危患者30岁以下人群缺乏有阿司匹林进行一级预防的证据故不推荐使用。 80岁以上老人获益增加，但胃肠道出血风险也明显增加，应仔细权衡获益－风险比，并与患者充分沟通后决定是否使用阿司匹林。

5 阿司匹林用于一级预防显著减少主要心血管事件
阿司匹林在心血管疾病一级预防中的效益已经得到6项大规模随机临床试验的证实，包括英国医师研究（BDT）、美国医师研究（PHS）、血栓形成预防试验（TPT）、高血压最佳治疗研究（HOT）、一级预防研究（PPP）和妇女健康研究（WHS）。

6 对全部6项一级预防试验的资料进行汇总分析，结果表明，阿司匹林用于一级预防使主要心血管事件减少15%，心肌梗死相对风险降低30%。
出血并发症的相对风险增加69%，主要危险来自于胃肠道和颅外出血，出血性脑卒中风险有所增加。 该研究提示未来10年心血管事件风险﹥8%的个体服用阿司匹林获益大于风险。

7 前5项试验纳入人群以男性为主，除BDT外，其他4项试验均显示阿司匹林可作为心血管疾病的一级预防，特别是可显著降低心肌梗死的危险。
WHS结果则显示，女性人群的主要获益是减少脑卒中，特别是缺血性脑卒中。

8 阿司匹林的效益存在性别差异 这些结果表明，采用阿司匹林进行一级预防能显著减少主要心血管事件，其中男性人群主要获益是降低心肌梗死危险，女性人群主要获益是降低缺血性脑卒中危险。

9 为什么存在性别差异？ 代谢过程有性别差异，女性的阿司匹林药理作用相对较弱; 脑卒中和心肌梗死的发生率有性别差异，女性发生脑卒中多于心肌梗死，男性则相反; 阿司匹林抵抗的发生率有性别差异，女性高于男性。

10 2009年抗血栓治疗试验协作组（Antithrombotic Trialists’Collaboration, ATT)对6项阿司匹林一级预防试验重新进行汇总分析，结果显示：对于未来10年严重心血管事件风险﹤6%的个体，阿司匹林使每年心血管事件风险降低12%，脑出血发生率从0.03%升至0.04%，胃肠道和颅外出血发生率从0.7%增加至1.0%。

11 阿司匹林对男性和女性的心血管预防作用并无差异性。
老年、男性、糖尿病、高血压患者既为血栓高危人群，同时也是出血高危人群。该研究提示，使用阿司匹林进行心血管一级预防要评价获益-出血风险比。 对于未来10年严重心血管事件风险﹤ 6%的个体，应用阿司匹林进行心血管一级预防风险大于获益。

12 在获益-风险比合理的人群中 推荐长期使用阿司匹林

13 评估获益/风险时，必须考虑患者的年龄和10年冠心病危险。对于获益与风险接近的患者，应通过协商决定是否使用阿司匹林.
当预期获益远超过风险时，阿司匹林的推荐力度增强。

14 阿司匹林获益超过胃肠道出血风险的危险水平
男性 女性 年龄 10年冠心病危险 45～59岁 ≥4％ 55～59岁 ≥3％ 60～69岁 ≥9％ ≥8％ 70～79岁 ≥12％ ≥11％ 适用于不使用非甾体类抗炎药、且无胃肠道症状或溃疡病史的成人，获益是指男性预防心肌梗死、女性预防脑卒中。同时使用非甾体类抗炎药或有溃疡病史的患者胃肠道出血风险成倍增加，须另行计算获益/风险。

15 除BDT外，其他5项试验均显示阿司匹林伴随着显著增高的出血风险，这种风险没有性别差异。
最常见的大出血部位是胃肠道，最常见的小出血类型是鼻衄和碰撞后容易发生皮下出血，出血性脑卒中的风险亦增高。 因此，阿司匹林用于一级预防能显著减少心血管病事件，但也显著增加出血的风险，只有在获益/风险合理的人群中，才能推荐长期使用阿司匹林。

16 系列研究显示，阿司匹林导致胃肠道出血的高危因素包括：高龄（﹥60岁），有上消化道疼痛症状、消化道溃疡或者出血史、正在使用NSAID、糖皮质激素类药物。
ACC/AHA/ACG共同发布《减少抗血小板药物和非甾体类抗炎药物(NSAID)导致胃肠道并发症的专家共识》，建议谨慎权衡抗血小板治疗获益和出血风险，胃肠道出血高危患者如需服用阿司匹林，建议联合应用质子泵抑制剂或者H2受体拮抗剂，根除幽门螺杆菌。

17 人群的心血管危险程度是指该人群在今后若干年内发生主要心血管事件的概率。2002年美国预防署特别工作组（USPSTF）发表阿司匹林用于心血管病一级预防的声明，指出对于5年内发生冠心病事件危险性≥3％的患者，使用阿司匹林有合理的获益/风险；40岁以上男性、绝经后妇女、以及有冠心病危险因素如高血压、糖尿病或吸烟的年轻人可考虑阿司匹林治疗。

18 USPSTF最近修订了阿司匹林用于心血管病一级预防的推荐内容
45～79岁的男性，在降低心肌梗死的获益超过增加胃肠道出血的风险时，推荐阿司匹林; 55～79岁的女性，在降低缺血性脑卒中的获益超过增加胃肠道出血的风险时，推荐阿司匹林; 80岁以上老年人群中，现有资料不足以评价阿司匹林用于一级预防的效益与风险; 不推荐55岁以下妇女用阿司匹林预防脑卒中或45岁以下男性用阿司匹林预防心肌梗死。

19 其他指南也推荐阿司匹林用于心血管病一级预防。
美国心脏协会在心血管病和脑卒中一级预防指南中指出，高危患者，特别是10年冠心病事件危险性≥10％的患者，应使用阿司匹林75～165mg/d。 欧洲2007年版高血压指南中指出，高危和极高危的高血压患者在血压有效控制后可使用阿司匹林75～100mg/d。

20 美国糖尿病协会指南推荐对于心血管病危险增高的1型或2型糖尿病患者（年龄＞40岁或伴有其他危险因素如心血管病家族史、高血压、吸烟、血脂异常或蛋白尿），应采用阿司匹林进行一级预防（75～165mg/d）。

21 Thanks!

22 Aspirin in the Primary Prevention of Cardiovascular Disease
Department of Cardiology, Daping Hospital,Third Military Medical University 第三军医大学大坪医院心内科 Chunyu Zeng （曾春雨）、Chengming (杨成明)

23 Low dose aspirin(75–100 mg/d ) are suggested as the primary prevention of cardiovascular disease in several populations by 2009 China Expert Consensus of Aspirin   

24 Man aged 45~79 years , with a 10-year risk of CAD 4-12％, without the high risk of gastrointestinal bleeding. Women aged 55~79 years , with a 10-year risk of ischemic stroke 3-11％, without the risk of gastrointestinal bleeding. Diabetic patients > 40 years of age , or > 30 years of age with other cardiovascular risk factor, such as family history of premature cardiovascular disease, hypertension, smoking, dyslipidaemia, albuminuria.

25 Hypertensive patients with blood pressure controlled（＜150/90mmHg）, at the same time one of the following condition: ① > 50 years of age,② target organ damage, including moderately high levels of plasma creatinine,③diatetes Combined with more than three of the following risk factors: ①Dyslipidaemia; ② smoking; ③obesity; ④ > 50 years of age; ⑤ Family history of premature cardiovascular disease.

26 Due to lacking of strong clinical evidence of aspirin in the primary prevention in the patients < 30 year old, even the 10-years risk of CAD ≥10％, aspirin are not suggested to be used. Although there is benefit for the patients > 80 years old, the risk of gastrointestinal bleeding also is increased, before using the aspirin, the communication between doctor and patients should be done well.

27 Aspirin in the primary prevention reduce main cardiovascular events
The benefits of aspirin in primary prevention of cardiovascular disease were confirmed by six large scale randomized controlled trial , including the British Doctors' Trial (BDT), the Physicians' Health Study (PHS), the Thrombosis Prevention Trial (TPT), the Hypertension Optimal Treatment (HOT) Study , the Primary Prevention Project (PPP), Women's Health Study (WHS).

28 The meta-analyses of 6 trials indicate aspirin yielded a 15% reduction in cardiovascular events, 30% reduction in relative risk ratio of myocardial infarction, However, 69% higher risk of bleeding, including major gastrointestinal and extracranial bleeds, with an increasing risk of haemorrhagic stroke. This research indicate that individual  presents a 10-year risk of CAD ≥8％, the benefits is more than the risks.

29 Except British Doctors' Trial (BDT), all the other 4 trials showed that low-dose of aspirin in the primary prevention decreases the risk of cardiovascular events, especially the risk of myocardial infarction in men. Women's Health Study (WHS) showed that the major benefits of aspirin in women is to reduce the risk of stroke, especially ischemic stroke.

30 Difference for the effect of aspirin between man and woman
Aspirin reduces main cardiovascular events, especially reduces the risk of myocardial infarction in man, while the risk of stroke in woman.

31 Reason for the sex difference:
Different metabolic process: effect of aspirin pharmacologic action is relatively weaker in woman. Different incidence rate of stroke and myocardial infarction:. More stroke in women, while more cardiac infarction in men. Different aspirin intolerance: women is popular than men.

32 Different Opinion Antithrombotic Trialists’ Collaboration Study (2009): In those patients with predicted 10-year risk of CAD<6%, aspirin yielded 12% reduction of annual incidence of vascular events, the incidence of cerebral hemorrhage was increased from 0.03% to 0.04%, the incidence of gastrointestinal and extracranial bleedings was increased from 0.7% to 1.0%. The effects of aspirin in the primary prevention seemed no different between men and women.

33 The aged, male、diabetes and hypertension are not only the risk factor of thrombolisis, but also the risk factor of haemorrhage. The balance between the benefit and the risk of bleedings should be assessed before using the aspirin in primary prevention. The individuals with predicted 10-year risk of CAD < 6%, adding aspirin in primary prevention get more harm than the benefits.

34 Aspirin are suggested to be used for long-term period in those patients with reasonable balance of risk and benefit

35 Age and 10-years risk of CAD is the major factors to assess the benefits and hazards of aspirin in primary prevention. The aspirin are strongly suggested to be used in those patients with more benefit than hazard.

36 The Benefit of Aspirin is Superior to the Risk of Gastrointestinal Bleeding
male female age 10 years CAD risk 45～59 ≥4％ 55～59 ≥3％ 60～69 ≥9％ ≥8％ 70～79 ≥12％ ≥11％ non-steroid anti-inflammatory drug; proton pump inhibitor

37 Except British Doctors' Trial (BDT), the other 5 trials showed there is a bleeding risk of aspirin in the primary prevention of cardiovascular events, and this risk had no sex difference. Gastrointestinal bleeding, peptic ulcers, self-reported hematuria, easy bruising, and nose bleeding were significantly more common. Only when benefit/risk is reasonable, aspirin is recommended to be used for long-term period.

38 U.S. Preventive Services Task Force (USPSTF): aspirin in the primary prevention
Man aged 45～79 years. the benefits of reduce the risk of myocardial infarction exceed the risk of gastrointestinal bleeding. Aspirin is suggested to be used. Woman aged 55～79 years，the benefits of reduce the risk of ischemic stroke exceed the risk of gastrointestinal bleeding. Aspirin is suggested to be used.

39 The aged persons >80 years, aspirin therapy are not suggested because the benefits and harm of aspirin in the primary prevention are not confirmed. Woman aged <55 years and man <45 years are not suggested to use aspirin in the prevention of myocardial infarction.

40 Other guides also recommend aspirin in primary prevention of cardiovascular disease
ACC indicates for high risk patients, especially 10-year risk of CAD ≥10％, recommend aspirin (75–165 mg/d) for cardiovascular disease and stroke primary prevention. Europe 2007 hypertension guide indicates high risk and sky-high risk hypertension patients approve aspirin (75–100 mg/d) after controlling blood pressure well.

41 ADA recommends to use aspirin (75–165 mg/d) in type 1 or 2 diabetic patients with higher cardiovascular risk (age＞40 years, family history of cardiovascular disease, hypertension, smoking, dyslipidaemia, albuminuria.) American College of Chest Physicians (ACCP) guideline indicates for patients with at least moderate risk for a cardiovascular event (based on age and cardiac risk factor profile with a 10-year risk of a cardiac event of > 10%), recommend to use 75–100 mg aspirin daily without clopidogrel.

42 Thanks!