阿司匹林的研发历史与作用机制概述PPT参考课件.ppt

1、阿司匹林的研发历史与作用机制概述,1,目录,2,1.阿司匹林的历史 2.阿司匹林一级预防研究 3.阿司匹林未来的循证医学支持,2,3,1897-08-10：菲利克斯霍夫曼首次合成高纯度性质稳定的乙酰水杨酸,1899-03-06: ASPIRIN,作为一个商标 正式在柏林帝国商务部专利局注册,1969: 阿司匹林作为止痛药， 伴随阿波罗11号首次登月升空,3,1985-10-09:美国卫生与民众服务部长玛格丽特赫克勒宣布：一天一片阿司匹林，有效预防第二次心肌梗死发作,1982: Sir John Vane爵士因发现阿司匹林的作用机制而获得诺贝尔奖,1988: 轰动一时的“内科健康医师研究”公布：

2、阿司匹林降低心脏事件发生44%,4,5,一路走来,FDA批准阿司匹林用于TIA或脑卒中的二级预防,FDA推荐阿司匹林做为预防心脏事件发生的常规用药,1971年，拜耳阿司匹林加维生素C的泡腾片问世；1993年，拜耳阿司匹林肠溶片上市。,1899年3月6日，阿司匹林的发明专利申请被通过,拜阿司匹灵100mg在中国上市,规范使用阿司匹林中国专家共识达成,SFDA批准拜阿司匹灵100mg肠溶片用于心肌梗死一级预防,阿司匹林上市,1898年,1980年,1996年,2003年,2009年,2006年,目录,6,1.阿司匹林的历史 2.阿司匹林一级预防研究 3.阿司匹林未来的循证医学支持,6,自1988年

3、众多研究证实了阿司匹林在心脑血管事件一级预防中的作用,7,坚实的循证证据：一级预防,写入我国医学生的教科书,8,长期服用阿司匹林和给予有效的降血脂治疗可促使粥样斑块稳定，减少血栓形成，降低不稳定型心绞痛和心肌梗死的发生率。,如无禁忌，急性冠状动脉综合征后应该无限期应用阿司匹林,如果存在动脉粥样血栓形成的危险因素，如患糖尿病，或对于高血压患者，如果年龄大于50岁或者存在高脂血症、糖尿病等，应口服阿司匹林预防,一级预防(75100mg/d),Physicians Health Study (PHS): design,CV, cardiovascular; MI, myocardial infarc

4、tion. 1. Steering Committee of the Physicians Health Study Research Group. N Engl J Med 1989;32112935.,Section 4,9,内科医师健康研究（PHS):设计,9,内科医师健康研究 (PHS): 结果,首次心肌梗死风险降低44% 致死性心肌梗死风险降低66% 非致死性心肌梗死风险降低41% 严重血管事件风险降低18%,试验提前终止 大部分终点降低程度极其显著,*Nonfatal MI, nonfatal stroke, cardiovascular death. MI, myocardial

5、 infarction. Steering Committee of the Physicians Health Study Research Group. N Engl J Med 1989;321:12935.,Section 4,10,Physicians Health Study (PHS): results,The trial was terminated early there was an impressive reduction in most endpoints,44% reduction in risk of first MI 66% reduction in risk o

6、f fatal MI 41% reduction in risk of nonfatal MI 18% reduction in risk of severe vascular events*,10,Physicians Health Study (PHS): results,CRP, C-reactive protein; MI, myocardial infarction. 1.Steering Committee of the Physicians Health Study Research Group. N Engl J Med 1989;321:12935; 2. Ridker PM

7、, et al. N Engl J Med 1997;336:9739.,Should you wish to use this slide outside Bayer Schering Pharma, please contact the publisher for permission,Section 4,11,内科医师健康研究（PHS):结果,安慰剂,阿司匹林,心肌梗死相对风险（%）,血浆C-反应蛋白的四分位数,11,Hypertension Optimal Treatment (HOT) trial: design,ACE, angiotensin converting enzyme;

8、 CV, cardiovascular; MI, myocardial infarction. 1. Hansson L, et al. Lancet 1998;351:175562.,Section 4,12,高血压最佳治疗研究（HOT)：设计,12,高血压最佳治疗研究（HOT）：结果,CV, cardiovascular. 1. Hansson L, et al. Lancet 1998;351:175562.,Section 4,13,事件比率（%）,阿司匹林75毫克/天 （n=9399),不服用阿司匹林,（n=9391）,主要心血管事件降低 （p=0.03）,13,Hypertensi

9、on Optimal Treatment (HOT) trial: results,MI, myocardial infarction. 1. Hansson L, et al. Lancet 1998;351:175562.,Section 4,14,高血压最佳治疗研究（HOT)：结果,事件比率（%）,阿司匹林75毫克/天 （n=9399),首次心肌梗死降低 （p=0.002）,不服用阿司匹林,（n=9391）,14,Aspirin was most beneficial in hypertensive patients with CKD*,15,*Based on a sub-analys

10、is of the HOT study. CI, confidence interval; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; GFR, glomerular filtration rate; MI, myocardial infarction. 1. Jardine MJ, et al. J Am Coll Cardiol 2010;56:95665.,低剂量阿司匹林使患有慢性肾脏病的高血压患者主要心血管疾病风险降低66%, 卒中风险降低79% ，心血管死亡率降低64%,S

11、hould you wish to use this slide outside Bayer Schering Pharma, please contact the publisher for permission,阿司匹林使慢性肾脏病的高血压患者获益最大化,Low-dose aspirin reduced major CVD by 66%, stroke by 79% and CV mortality by 64% in hypertensive patients with CKD,58,心血管死亡数,总体死亡数,15,Hypertension Optimal Treatment (HOT)

12、 trial: conclusions,“除了抗高血压治疗获益外，阿司匹林使致死性和非致死性严重心肌梗死大幅获益，其发生率降低多达36% (可能获益为 15 -51%), 并且每1000例患者使用阿司匹林治疗一年能够预防1-5例心肌梗死发生(糖尿病患者为2.5例心肌梗死/1000人年)。” “慢性肾脏病的患者与正常肾功能的患者相比阿司匹林治疗显著阻止了更多心血管事件, 心血管事件死亡数, 各种原因死亡数 。所有心血管事件获益似乎比出血风险更有价值。”,CV, cardiovascular; CKD, chronic kidney disease; MI, myocardial infarcti

13、on. 1. Hansson L, et al. Lancet 1998;351:175562.,Section 4,16,高血压最佳治疗研究（HOT）：分析,“The investigation of the effects of a small dose of aspirin versus placebo in treated patients with hypertension provides very clear evidence of a substantial beneficial action of aspirin on fatal and nonfatal acute MI,

14、 the incidence of which was reduced by as much as 36% (with the possibility of a benefit between 15 and 51%), and the prevention of 15 MIs per 1,000 patients treated for 1 year (and 2.5 MIs per 1,000 patient-years in patients with diabetes mellitus) in addition to the benefit achieved by antihyperte

15、nsive therapy.” “Aspirin therapy prevented significantly more CV events, CV deaths, and all-cause deaths in patients with CKD than in subjects with normal kidney function. The overall CV benefits appear to outweigh bleeding risks.”,16,Womens Health Study (WHS): design,CV, cardiovascular; MI, myocard

16、ial infarction. 1. Ridker PM, et al. N Engl J Med 2005;352:1293304.,Section 4,17,女性健康研究（WHS）：设计,17,Womens Health Study (WHS): results,CV, cardiovascular. 1. Ridker PM, et al. N Engl J Med 2005;352:1293304.,Should you wish to use this slide outside Bayer Schering Pharma, please contact the publisher

17、for permission,总体脑卒中风险降低17% (p=0.04),缺血性脑卒中风险降低24% (p=0.009),Section 4,18,女性健康研究（WHS）：结果,17% reduction in the risk of total stroke (p=0.04),24% reduction in the risk of ischaemic stroke (p=0.009),脑卒中累计发生率,缺血性脑卒中累计发生率,随访（年）,随访（年）,阿司匹林,安慰剂,18,Womens Health Study (WHS): aspirin is effective in women ag

18、ed 65 years,CV, cardiovascular; MI, myocardial infarction. 1. Ridker PM, et al. N Engl J Med 2005;352:1293304.,Section 4,19,女性健康研究（WHS）：阿司匹林使年龄 65岁女性获益,19,JPAD study: design,IHD, ischaemic heart disease; JPAD, Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes; PAD, peripheral artery disease. 1. Ogawa H, et al. JAMA 2008;300:213441.,Section 4,20,JAPD研究：设计,the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes study,20,JPAD study: results,JPAD, Japanese Primary Prevention of Atherosclerosis