《高血压合理用药》PPT课件.ppt

1、从指南到实践-高血压合理用药几个最新要点讨论,中国医学科学院 北京协和医学院 阜外心血管病医院 顼志敏 Xu Zhimin,我国高血压患病率愈来愈高,全国患病人数已超过2.0亿,中国居民营养与健康现状调查。卫生部、科技部、统计局，2004、10、12,我国18岁及以上居民高血压患病率为18.8%,中国高血压控制率,西方七国的高血压控制率,26.8,13.0,9.3,5.7,7.7,5.0,11.6,30,25,20,15,10,5,0,USA,加拿大,英国,芬兰,德国,西班牙,意大利,Wolf-Maier K et al, Hypertention Treatment and control,

2、 Hypertension 2004:43:10-17,控制率,降压本身的益处,平均降低 卒中发生率 3540% 心肌梗死 2025% 心力衰竭 50%,JNC 7,收缩压降低1012mmHg或舒张压降低5-6mmHg,1、高血压治疗四大目标,长期、有效、平稳控制血压水平 预防(逆转)心、脑、肾等靶器官的损害 减少心、脑血管疾病的发病和死亡循证医学 改善生活质量,亚临床靶器官损害之保护 (2009,oct ESH Reappraisal) Evidence on the important prognostic role of subclinical organ damage continue

3、s to grow. In both hypertensive patients and the general population, the presence of electrocardiographic and echocardiographic LVH, a carotid plaque or thickening, an increased arterial stiffness, a reduced eGFR (assessed by the MDRD formula), or microalbuminuria or proteinuria substantially increa

4、ses the total cardiovascular risk, usually moving hypertensive patients into the high absolute risk range. 合并亚临床靶器官损害常为高危者：LVH,颈动脉斑块、增厚硬化， eGFR下降，微量/蛋白尿。 -Journal of Hypertension 2009, 27:21212158,血压目标 所有患者 140/90 140/90 DM/肾病 130/80(DM) 130/80 冠心病：130/80 mm Hg (2007/2009年欧洲高血压指南) *老年SBP难于140可适当灵活些(

5、尤低危者)， 老年收缩压可降至150 mm Hg以下,Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document (2009,oct ESH) -Journal of Hypertension 2009, 27:21212158,血压目标 (2009,oct ESH Reappraisal) there is sufficient evidence to recommend that SBP be lowered bel

6、ow 140mmHg (and DBP below 90mmHg) in all hypertensive patients, both those at low moderate risk and those at high risk. Evidence is only missing in the elderly hypertensive patients, in whom the benefit of lowering SBP below 140mmHg has never been tested in randomized trials. 不论高危、低中危：BP140/90 mmHg;

7、 高龄老年缺少具体证据 .-Journal of Hypertension 2009, 27:21212158,血压目标 (2009,oct ESH Reappraisal) post hoc analyses of trial data indicate a progressive reduction of cardiovascular events incidence with progressive lowering of SBP down to about 120mmHg and DBP down to about 75mmHg. 直至BP120/75, 低比高好；除非严重动脉粥样硬化

8、，不会发生J-曲线现象 A J-curve phenomenon is unlikely to occur until lower values are reached, except perhaps in patients with advanced atherosclerotic artery diseases. -Journal of Hypertension 2009, 27:21212158,血压目标 低限？ (ESH June, 2009 ) Key among the changes will be the recommendation of a lower threshold

9、level-around 120 mm Hg systolic and 70 mm Hg diastolic-below which it could be dangerous to reduce blood pressure in high-risk individuals, representing the so-called J-curve phenomenon, Mancia said. J-Curve: A Narrow Window of Optimum BP for High-Risk Individuals “J形曲线”可能存在，有些特定高危患者血压不宜过低（120/70） -

10、June 16, 2009 (Milan, Italy) The European Society of Hypertension (ESH),血压达标 (2009,oct ESH Reappraisal) Each drug class has contraindications as well favorable effects in specific clinical settings. The choice of drug(s) should be made according to this evidence. The traditional ranking of drugs int

11、o first, second, third, and subsequent choice, with an average patient as reference, has now little scientific and practical justification and should be avoided. 每种药物均有利弊：应循证选药； 强调个性化用药，避免一线、二线、三线 -Journal of Hypertension 2009, 27:21212158,血压目标 (2009, June ESH) these will remain pretty much the same

12、 as in 2007, he said, with a treatment threshold of 140/90 mm Hg or greater for general hypertension, and a therapy goal of 140/90 mm Hg for this population. For high-risk individuals, the treatment threshold is 130/85 or greater and the treatment goal should be 130/80 mm Hg . 开始用药： 目标： 一般患者： 140/90

13、； 140/90； 高危患者： 130/85； 130/80； -June 16, 2009 (Milan, Italy) The European Society of Hypertension (ESH),何时开始用药 (2009,oct ESH Reappraisal) it appears reasonable to recommend that, in grade 1 hypertensives (SBP 140159mmHg or DPB 9099mmHg) at low and moderate risk, drug therapy should be started after

14、 a suitable period with lifestyle changes. Prompter initiation of treatment is advisable if grade 1 hypertension is associated with a high level of risk, or if hypertension is grade 2 or 3. 立即用药：a）2或3级高血压; b）1级HT +高危 改善生活方式后用药：1级HT +低、中危,何时开始用药 (2009,oct ESH Reappraisal) In patients with high normal

15、 BP (BP 130139/ 8589mmHg) uncomplicated by DM or previous CV events, no trial evidence is available of treatment benefits, except for a delayed onset of hypertension (crossing the 140/90mmHg cutoff). Initiation of anti-HT drug therapy in DM with high normal BP is presently unsupported by prospective

16、 trial evidence. For the time being, it appears prudent to recommend treatment initiation in high normal BP diabetic patients if subclinical organ damage (particularly microalbuminuria or proteinuria) is present. 谨慎推荐：高正常血压：合并DM+亚临床靶器官受损，或CV事件病史者，开始用药（尽管缺乏证据）,2、治疗策略（中国） 几周内渐降血压至目标, 更长/更短期间？（几天？） 推荐长

17、效剂，持续24小时、T/P50%， Qd，提 高顺从、平稳降压 据血压水平、RF、TOD、ACC,选单或多药联合 制定个性化方案：2级以上高血压常需联合用药，配 合非药物疗法,达标快慢： (2009, June ESH) In 2007, we took a strong stance in favor of combination treatment. This has been shown again-trials such as ACCOMPLISH, ADVANCE, HYVET, ASCOT and ONTARGET are changing the picture. We have

18、 to lower BP rather quickly in these patients to try to prevent a catastrophe, and more recently, studies have shown there is less discontinuation of treatment in this patient population if treatment is started with combination therapy, Mancia said. 对高危患者更倾向于：联合用药、尽快达标、预防事件 -June 16, 2009 (Milan, It

19、aly) The European Society of Hypertension (ESH),近期的大型高血压临床试验带来的启示,降压越显著，预后越佳; 达标越早，预后越好; 2/3高血压需联合治疗才能达标; 降压会对代谢影响; 因此，联合治疗至关重要,Volpe M, 2006,3、药物治疗战略理念,3-1用药模式： 1）套餐模式：195060s 2）席餐模式: 197080s 3）自助餐模式: 19902000s,联合治疗的合理性,增加疗效 降压协同/附加作用 不同病理生理机制互补 减少副作用 不良反应互抵 互减剂量,3-2常用五类药物及其配方： RAS拮抗剂：ACEI(普利) ARB(

20、沙坦) 钙拮抗剂： CCB(地平等) 利尿剂 (噻嗪等) Beta阻滞剂： BB(洛尔等),2009 ESC/ESH 专家意见,利尿剂,CCB,ARB,ACEI,3-3 2007ESC/ESH指南推荐联合: 噻嗪类利尿剂与ACEI， 噻嗪类利尿剂与ARB， 钙拮抗剂与ACEI， 钙拮抗剂与ARB， 钙拮抗剂与噻嗪类利尿剂， - 受体阻滞剂与二氢吡啶类钙拮抗剂。,保护心脑肾作用突出： ACEI /ARB+CCB (2009, June ESH) a number of important trials have added new evidence in favor of the protect

21、ive effects of ACE inhibitors, ARBs, and CCBs and have reinforced the position of these drugs as options to treat hypertension and other conditions such as heart failure and renal disease. The evidence is now in favor of giving such patients a blocker of the renin-angiotensin system (RAS)-such as an

22、 ACE inhibitor or ARB-with a calcium-channel blocker or diuretic. However, he stressed: This does not mean that other combinations cannot be used or are not useful. -June 16, 2009 (Milan, Italy) The European Society of Hypertension (ESH),保护心脑肾作用突出： (2009,oct ESH) In no less than 1520% of hypertensiv

23、e patients, BP control cannot be achieved by a two-drug combination. When three drugs are required, the most rational combination appears to be a blocker of the renin angiotensin system, a calcium antagonist, and a diuretic at effective doses. 至少1520% 高血压患者，需要三联用药：最合理方案： RAS拮抗剂+CCB+利尿剂 -Journal of H

24、ypertension 2009, 27:21212158,合理联合用药方案： (2009,oct ESH) As mentioned in the 2007 ESH/ESC guidelines, several two-drug combinations are suitable for clinical use.However, trial evidence of outcome reduction has been obtained particularly for the combination of a diuretic with an ACE inhibitor or an an

25、giotensin receptor antagonist or a calcium antagonist, and in recent large-scale trials for the ACE inhibitor/calcium antagonist combination. The angiotensin receptor antagonist/calcium antagonist combination also appears to be rational and effective. These combinations can thus be recommended for p

26、riority use. 利尿剂+ACEI /ARB /CCB; CCB +ACEI /ARB,合理联合用药方案： (2009,oct ESH) The combination of two antihypertensive drugs may offer advantages also for treatment initiation, particularly in patients at high cardiovascular risk in which early BP control may be desirable. Whenever possible, use of fixed

27、dose (or single pill) combinations should be preferred, because simplification of treatment carries advantages for compliance to treatment. 在高危病人，两药联合还可尽快达标 应优先应用固定剂量的单片剂复方： 使治疗简化、顺应性提高,CCB/ACEI联合治疗更显著降低心血管发病率和死亡率,Kenneth Jamerson et al. 57th annual scientific session of ACC,至首发CV事件的时间 (天),主要终点：心血管发

28、病率与死亡率；中期数据2008年3月,4-2、2007欧洲高血压指南: 长效钙通道阻滞剂：没有强制禁忌证。 推荐用于: 脑卒中、 老年单纯收缩期高血压、 心绞痛、 左室肥厚、 颈动脉或冠状动脉粥样硬化、 妊娠妇女、 黑人高血压等。,4-2、2007欧洲高血压指南: ACEI ： ACEI优先适应证共10项： 心力衰竭、左室肥厚、左室功能异常、 心肌梗死后、 糖尿病肾病、非糖尿病肾病、 颈动脉粥样硬化、 蛋白尿或微量蛋白尿、 心房颤动 和 代谢综合征等,4-2、2007欧洲高血压指南: ARB优先适应证： 1.老年患者 2.糖尿病 3.肾功能不全 4.脑卒中 5.冠心病和心衰 6.房颤 7.代谢

29、综合征,药物选择： (2009,oct ESH) The 2007 ESH/ESC guidelines conclusion that diuretics, ACE inhibitors, calcium antagonists, angiotensin receptor antagonists, and b-blockers can all be considered suitable for initiation of antihypertensive treatment, as well as for its maintenance, can thus be confirmed. Th

30、is is of crucial importance because cardiovascular protection by antihypertensive treatment substantially depends on BP lowering per se, regardless of how it is obtained. 仍支持2007ESH/ESC高血压指南：合理选择：利尿剂、ACEI、CCB、ARB、Beta阻滞剂 无论如何治疗，降压是硬道理。,Beta阻滞剂： (2009, June ESH) The totality of evidence now shows dif

31、ferent conclusions for different patient populations, he said. For example, for stroke prevention, beta blockers are inferior to calcium antagonists, but for congestive heart failure prevention, beta blockers are superior to calcium antagonists and similar to other drugs, 对脑卒中预防，BB弱于CCB; 对心衰， BB强于CC

32、B -June 16, 2009 (Milan, Italy) The European Society of Hypertension (ESH),Beta阻滞剂： (2009,oct ESH) a recent meta-analysis of 147 randomized trials (the largest meta-analysis so far available) reports only a slight inferiority of b-blockers in preventing stroke (17% reduction rather than 29% reductio

33、n with other agents), but a similar effect as other agents on preventing coronary events and heart failure, and a higher efficacy than other drugs in patients with a recent coronary event 目前最大（n=147）RCT荟萃分析示：与其他药物比，Beta阻滞剂， 预防脑卒中方面略弱； 预防冠脉事件和心衰，相同； 预防近期冠脉事件，较好。,RAS拮抗剂： (2009,oct ESH) ONTARGET has sh

34、own telmisartan not to be statistically inferior to ramipril as far as the incidence of a composite endpoint including major cardiac outcomes are concerned. A similar incidence of strokes was also observed on both treatments. Recent meta-analyses including older and more recent trials confirm the co

35、nclusion that ACE inhibitors and angiotensin receptor antagonists have the same preventive effect on myocardial infarction ONTARGET示：预防冠脉事件和预防脑卒中 方面，替米沙坦与雷米普利相同； 最近荟萃分析示：预防心梗疗效，ARB与ACEI相同。,新型降压药： (2009,oct ESH) Drugs acting via direct renin inhibition are the only new classes of antihypertensive age

36、nts that have recently become available for clinical use. Several additional new classes are under an early investigational phase. Selective antagonism of endothelin receptors holds some promise to improve rate of BP control in hypertensive patients resistant to multiple drug treatment. 直接肾素抑制剂； 选择性

37、内皮素受体拮抗剂。,个性化选药： (2009, June ESH) Classifying agents as first choice, second choice, third choice, etc, betrays reference to an average patient who hardly exists in clinical practice, he said, adding: It is much better to indicate which drug might be preferred in which patient under which circumstan

38、ce. All drugs have advantages and disadvantages, and we have to try to see in which conditions the advantages of a drug come out. 最好用药模式： 在合适的情况，选择合适的药物， 用于合适的病人； -June 16, 2009 (Milan, Italy) The European Society of Hypertension (ESH),老年高血压： (2009, Oct ESH) At variance from previous guidelines, evi

39、dence is now available from an outcome trial (HYVET) that antihypertensive treatment has benefits also in patients aged 80 years or more. BP-lowering drugs should thus be continued or initiated when patients turn 80, starting with monotherapy and adding a second drug if needed. The decision to treat

40、 should thus be taken on an individual basis, and patients should always be carefully monitored during and beyond the treatment titration phase 80岁或以上的老年高血压降压也可获益； 常常一种药开始，如需要再加另一种； 小心谨慎、个性化。,糖尿病高血压： (2009, Oct ESH) In diabetes, combination treatment is commonly needed to effectively lower BP. A ren

41、inangiotensin receptor blocker should always be included because of the evidence of its superior protective effect against initiation or progression of nephropathy. 糖尿病合并高血压常需联合降压； 其中ARB因其优质的肾保护作用，不应缺少；,入选 ： 55Yr.冠心病或高危糖尿病患者，无心衰， n=25,620 随机接受： 雷米普利 10 mg /日（n=8576）, 或替米沙坦 80 mg /日 （n=8542）, 或 2药合用（

42、n=8502 ） . 平均 随访55 月.,ONTARGET2008ACC,结果1： 比雷米普利组，平均BP多降： 在替米沙坦组0.9/0.6mmHg； 2药合用组2.4/1.4mmHg. 试验结束时, 3组间主要复合终点相同 (心血管死亡, MI，卒中, 或心衰住院) . %: 雷16.5 ；替16.7 ；合16.3. Risk ratio (95% CI): 替vs雷1.01 (0.941.09); 合vs雷0.99(0.921.07); 比雷米普利组， 在替米沙坦组：咳嗽、血管性水肿较少，低血压症较多； 在2药合用组：低血压症、晕厥、肾功不全及高血钾发生率较 高，而且需透析的风险有增加趋

43、势.,ONTARGET2008ACC,结果2： 比雷米普利组(11.8%)，全因死亡无差别： 在替米沙坦组(11.6%)， Risk ratio (95% CI): 0.98 (0.901.07) 2药合用组(12.5%)：1.07 (0.981.16) 比雷米普利组(7%)，心血管病死亡无差别： 在替米沙坦组(7%)， Risk ratio (95% CI): 1.00 (0.891.12) 2药合用组(7.3%)：1.04 (0.931.17) 比雷米普利组(10.2%) ，肾功能受损： 在替米沙坦组10.6%)， Risk ratio (95% CI): 1.04 (0.961.14)

44、2药合用组(13.5%)：1.33 (1.221.44),ONTARGET2008ACC,结论: “对于无心衰的心血管病或者高危糖尿病患者, 替米沙坦可等效替代雷米普利,” 而且 “如何选择取决于病人和医生的倾向性以及不良反应的个体易感性.“ 另外， “与单用雷米普利相比，2药全剂量合用对该类病人并无额外益处（甚至有害）,”合用尽管能更显著降血压但并未见到更多的获益令人“困惑.,ONTARGET2008ACC,Dr John McMurray (University of Glasgow, Scotland) 点评: ONTARGET、 VALIANT 试验均显示 , ARB合用ACEI 并无

45、额外获益，甚至增加不良反应. 这与Val-HeFT及CHARM所显示的合用2药可增加获益的结果形成对比， 但应注意这2个心衰试验并未在所有患者使用全剂量（ full dose）的ACEI, 故未能肯定合用益处是来自心衰条件还是ACEI 的品种或剂量等用法方面。,ONTARGET2008ACC,降压作用：85-90% 降压外作用：15-10% 降压外作用依赖降压作用 降压疗效依赖： 1）降压幅度、基线血压、危险程度、并发 症及合并症，降压对象等。 2）合适的药物：品种、剂量、用法、时程 、配伍，等。,降压达标是关键，全面防治为根本,TRANSCEND研究结果,一般情况基线水平,一般情况基线水平,

46、TRANSCEND 研究的主要医学结论,心血管事件高危患者在TRANSCEND 研究中接受到了比HOPE研究中更佳的背景治疗的保护，年事件发生率明显更低。 因安慰剂对照组可以服用血管紧张素受体拮抗剂以外的降压药物，两组间的血压差别仅为4.2/2.2mmHg。替米沙坦使主要终点事件发生率下降8% (p=0.21, NS)。 与对照组相比，替米沙坦使心血管死亡、心肌梗死、卒中的复合终点发生率（ HOPE主要终点）显著下降 13% (p=0.048) 。对心血管保护程度与在ONTARGET 和 HOPE中的结果相似。 与对照相比，替米沙坦没有更多减少因心力衰竭而住院的情况发生。可能由于对照组已合用大

47、量利尿药、受体阻滞剂和钙通道阻滞剂 。 与对照组相比，替米沙坦使所有心血管原因入院率显著降低 (894 vs 980; p=0.025)。 替米沙坦耐受性好，坚持服用多 (639 vs. 705; p=0.055)。,51,20,332 例患者,2x2 析因设计，20,332 例50岁以上卒中患者,PRoFESS试验设计,Protocol Amendment 2 - ASA was deleted from C+ASA due to MATCH results in May, 2004: 2027 subjects treated for a maximum of 8 months with

48、C+ASA,52,主要终点: 复发卒中,* Covariates in Cox model are age, baseline ACE-inhibitor use, Modified Rankin, and baseline diabetes status.,10/05/2008,53,复发卒中-时间,*p-value for interaction=0.042,54,次要终点-时间,*p-value for interaction=0.004,55,分析,入选过早:中风发生到随机进入试验的天数的中位数为15天。治疗尚未显效，不良事件发生率高(lag)。 6个月后的明显获益与以往RAAS阻滞剂

49、试验的结果相一致。 2.5年的试验时间可能过短。 在安慰剂对照组不限制使用降压药物，两组间血压差 3.8/2.0mmHg，未能使再发中风或其它心脑血管事件的风险降低。需要进一步的试验：更长的试验时间和/或更显著的降压。,ONTARGET、TRANSCEND 结果: 进展与讨论David Fitchett. Vascular Health and Risk Management 2009:5,TRANSCEND 中性结果原因： 检验效能不够（under-powered study）, 并且高比例患者以前用ACEI. 研究显示： ARB 可以代替ACEI ,保护高危患者的血管. 指南开始推荐：AC

50、EI 和 ARBs 可以互换选择，用于保护血管，尤其在糖尿病高危患者. (Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada.Can J Diabetes. 2008;32 suppl 1:S1S201.),安慰剂,剂量增加,持续治疗,入选,单盲 2 wee

51、ks,2周,4周,8周,6月,10月,14月至研究结束 每4个月随访一次,75 mg,150 mg,300 mg,直至有 1,440 例主要终点事件发生为止,N=4,128,I-PRESERVE: 研究设计,厄贝沙坦,随机,入选时只能有 1/3 患者可以服用一种ACEI,随机、双盲、安慰剂对照研究,NYHA 分级 III/IV,超声 (左室肥大, 左心房 扩大),心电图 (左室肥大, 左束支 传导阻滞),胸片 (充血),I-PRESERVE: 入选标准,NYHA 分级 II - IV,充血性心衰住院 6 months,主要排除标准: SBP 160 mm Hg; 入组前 EF 2.5, 血红蛋

52、白 11,年龄 60岁 具有心衰症状 左室射血分数 LVEF 0.45,I-PRESERVE: 主要终点死亡率或研究所设定的心血管原因住院率,随机治疗时间（月）,主要终点事件累积发生率 (%),40 -,0 -,10 -,20 -,30 -,0,6,12,18,24,36,42,30,48,60,54,2067,1929,1812,1730,1640,1513,1291,1569,1088,497,816,2061,1921,1808,1715,1618,1466,1246,1539,1051,446,776,No. at Risk,厄贝沙坦,安慰剂,HR (95% CI) = 0.95 (0

53、.86-1.05) Log-rank p=0.35,安慰剂,厄贝沙坦,I-PRESERVE: 次要终点,因心衰死亡或住院,死亡,I-PRESERVE: 次要终点,心血管原因引起的死亡,心血管原因或心梗或中风 引起的死亡,治疗时间（月）,事件累积发生率 (%),No. at Risk,1504,1277,1726,974,589,2067,2007,1941,1908,1846,0 -,5 -,10 -,15 -,20 -,25 -,30 -,HR (95% CI) = 0.99 (0.86 1.13) Log-rank p=0.84,厄贝沙坦,安慰剂,1777,36,24,0,12,48,60

54、,54,42,30,6,18,安慰剂,厄贝沙坦,1461,1239,1695,932,546,2061,2006,1949,1891,1823,1764,治疗时间（月）,事件累积发生率 (%),No. at Risk,1569,1334,1784,1026,634,2067,2029,1976,1949,1893,0 -,5 -,10 -,15 -,20 -,HR (95% CI) = 1.01 (0.86 1.18) Log-rank p=0.92,厄贝沙坦,安慰剂,1833,36,24,0,12,48,60,54,42,30,6,18,安慰剂,厄贝沙坦,1521,1298,1761,980

55、,579,2061,2020,1974,1829,1877,1827,I-PRESERVE: 小结,I-PRESERVE研究入选的为老年患者，且女性占大多数，这与流行病学 HF-PEF 患者的分布特点相似。 虽然这些患者得到很好的治疗，但仍有较高的死亡率和心血管发病率。 厄贝沙坦并未降低主要终点死亡率和研究设定的心血管原因住院率，也没有降低预先设定的次要终点发生率。治疗可以良好耐受。,I-PRESERVE: 基线特点（一）,I-PRESERVE: 基线特点（二）,厄贝沙坦 (N = 2067),安慰剂 (N = 2061),137 15 79 9,136 15 79 9,临床指标,体重指数 (

56、kg/m2),29.6 5.3,29.7 5.3,心功能不全QOL (中位值, IQ range),42 (28 58),42 (27 58),实验室指标,血红蛋白 (g/dL),肌酐 (mg/dL),估计GFR (ml/min/1.73m2),N末端脑钠素愿, pg/ml (中位值, IQ range),14 2,14 2,1.0 0.34,1.0 0.32,72 22,73 23,320 (131 946),360 (139 987),除有特别标注外，均为平均值 标准差,0.59 0.09,0.60 0.09,31,30,射血分数,心电图 - 左室肥大 (%),收缩压 (mm Hg) 舒张

57、压 (mm Hg),I-PRESERVE: 基线治疗,32,30,降脂药物,59,58,抗血小板制剂,40,39,钙离子拮抗剂,59,58,Beta 阻滞剂,14,13,地高辛,26,25,ACEI,15,15,安体舒通,82,84,治疗药物 (%) 利尿剂,厄贝沙坦 (N = 2067),安慰剂 (N = 2061),38,39,27,28,研究期间服用该药的比例,72,72,ACTIVE I 厄贝沙坦或安慰剂 (n=9024),ACTIVE W 氯吡格雷+ASA 或 OAC (n=6507),ACTIVE 研究计划: 3项试验,有记录的 AF + 1 危险因素: 年龄 75, 高血压, 既

58、往卒中/TIA, LVEF45, PAD, 年龄55-74 + CAD或糖尿病,有OAC的禁忌症 或不愿使用,ACTIVE A 氯吡格雷+ASA 或 ASA (n=7554),无ACTIVE I的排除标准,部分析因设计,ACTIVE-I入选标准,The ACTIVE Investigators. AHJ. 2006;151(6):1187-93,房颤: 持续性、阵发性或永久性 合并心血管高危因素（至少有以下一项） 年龄 75 岁 原发性高血压 脑卒中史、一过性脑缺血发作史、非中枢神经系统血栓 左心室收缩功能异常伴左室射血分数45% 外周血管疾病(外周动脉血运重建史，截肢或间歇性跛行且踝臂收缩压比值0.9) 55-74岁且有以下任一项 需要药物治疗的糖尿病或 心梗史或冠心病史,68,符合研究的标准,入选： 所有符合ACTIVE W 或 ACTIVE A标准的患者 收缩压 110 mm Hg 排除： 已经使用血管紧张素受体拮抗剂，强制适应症或既往不能耐受 主要终点： 首次出现卒中、心梗或心血管死亡 首次出现卒中、心梗、心血管死亡或心衰住