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1、高血压合理用药最新要点讨论及处方分析,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,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)Ev
2、idence on the important prognostic role of subclinical organ damage continues 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
3、MDRD formula),or microalbuminuria or proteinuria substantially increases 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 140/90 140/90DM/肾病 130/80(DM)
4、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(尤低危者)，老年收缩压可降至150 mm Hg以下,血压目标 低限？(ESH June,2009)Key among the changes will be the recommendation of a lower threshold level-around 120 mm Hg systolic and 70 mm Hg diastolic-below which it could be dangerous to reduce blood pressure in high-
5、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）-June 16,2009(Milan,Italy)The European Society of Hypertension(ESH),血压达标(2009,oct ESH Reappraisal)Each drug class has contraindic
6、ations 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 into first,second,third,and subsequent choice,with an average patient as reference,has now little scientific and practical justificationand s
7、hould 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,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 asuitable period w
8、ith 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,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
9、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 to lower BP rather quickly in these patients to try to prevent a
10、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,Italy)The European Society of Hypertension(ESH),3、药物治疗战略理念,3-1用药模式：1）套餐模式：19
11、5060s2）席餐模式:197080s3）自助餐模式:19902000s,3-2常用五类药物及其配方：RAS拮抗剂：ACEI(普利)ARB(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：(2009,oct ESH)In no less than 1520%of hypertensive
12、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 reninangiotensin 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 Hypertension
13、2009,27:21212158,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 dose(or single pill)combinations sho
14、uld 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,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。,ACEI/ARB类药物的绝对禁忌证,妊娠血管神经性水肿高钾血症双侧肾动脉狭窄,4-2、2007欧洲高血压指南:ACEI：ACEI优先适应
15、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.代谢综合征,Beta阻滞剂：(2009,June ESH)The totality of evidence now shows different conclusions for different patient populations,he said.For example,for stroke prevention,bet
16、a 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CCB-June 16,2009(Milan,Italy)The European Society of Hypertension(ESH),Beta阻滞剂：(2009,oct ESH)a recent meta-an
17、alysis 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%reduction with other agents),but a similar effect as otheragents on preventing coronary events and heart failure,and a higher ef
18、ficacy than other drugs in patients with arecent 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 shown telmisartan not to be statistically inferior to ramipril as far as the incidence of a composite endpoint including major card
19、iac 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 conclusion that ACE inhibitors and angiotensin receptor antagonists have the same preventiveeffect on myocardial infarction ONTARGET示
20、：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。,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
21、which patient under which circumstance.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 pr
22、evious guidelines,evidence 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 d
23、ecision to treat should thus be taken on an individual basis,and patients should always be carefully monitored during and beyond the treatment titration phase80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 B
24、P.A reninangiotensin receptorblocker should always be included because of the evidence of its superior protective effect against initiation orprogression 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；,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
25、伍，等。,降压达标是关键，全面防治为根本,CAD 预防:140/90 任何有效抗高血压药物或联合CAD高危者:130/80 ACEI 或 ARB 或CCB或噻嗪利尿剂或联合稳定性心绞痛:130/80-Blocker 和ACEI 或 ARBUA/NSTEMI:130/80-Blocker(若血动学稳定)和 ACEI 或 ARBSTEMI:130/80-Blocker(若血动学稳定)和 ACEI 或 ARBLVD:120/80 ACEI 或ARB 和-blocker 和 醛固酮拮抗剂 和噻嗪 或 袢利尿剂 和 hydralazine/亚硝酸异山梨酯(黑种人),指南推荐汇总:BP 目标 mm Hg:
26、-AHA Scientific Statement 2007:Hypertension in Ischemic Heart Disease,处方1患者男，42岁，农民，高血压10余年，最高220/120 mmHg,无明显症状，未规律用药，否认其他病史，吸烟20年（20支/日），父亲有高血压脑出血病史。,处方1就诊查体：血压180/112 mmHg。心电图：左心室高电压，提示心肌肥厚，V4-6 ST段水平下移0.1-0.2 mV,且T波倒置，但2年内无明显动态性改变。心脏超声：左心室舒张功能减退，LA38 mm,IVS 13 mm,PW 11 mm,符合高血压左心室肥厚改变。尿常规（-）。血脂血
27、糖均在正常范围内。,处方1诊断：高血压 3级、高危,处方1：卡托普利（国产）25 mg Tid;双氢克尿噻 25 mg Qd,1周后12.5 mg Qd;尼群地平（国产）10 mg Tid；1周后加用阿司匹林100 mg Qd。,1周时复测血压110/70 mmHg，病人有时从平卧突然站立时感觉头昏不适,处方1：将尼群地平改为5 mg Bid，几天后头昏不适的症状消失，血压132/84 mmHg。,处方1：待2周后尼群地平10 mg Bid，余药同前，患者无不适症状，血压114/70 mmHg，维持长期治疗。1年后将卡托普利改为25 mg Bid,余药同前。每天治疗费用1角左右，血压2年来一直
28、维持于100-110/60-70 mmHg之间，无任何不适。,处方1：分析：（1）因该患者为中年男性、3级高危高血压，合并左心室肥厚、吸烟等危险因素，故降压目标应该120/80 mmHg。（2）开始用药时，曾因不适应，一度头昏不适，待治疗一段时间后大多数病人会逐渐适应的，可据具体情况随时调整用药。（3）目前，ACEI类药物的强适应症最多，故本方主药为卡托普利，最佳配角为双氢克尿噻，两者合用效果可翻倍。,处方1：分析：（4）因患者年轻、血压太高、病程长、未规律用药，故加尼群地平，以尽快达标、提高顺从性；如果年龄较大、非高危，用药及加量不必像本方那样“强烈”。（5）该患者达标后，长期维持摸索好的方
29、案，少花钱多获效益。,处方2患者男性，51岁，外企职员。发现高血压5年，最高血压180/120 mmHg，就诊时正在服用复方降压片2片，一天三次；血压忽高忽低，在160-150/100-90 mmHg范围；,处方2心脏超声示左心室肥厚:IVS及PW均为13 mm，空腹血糖6.3 mmol/L，尿常规蛋白（+），吸烟20年，20支/日。,处方2诊断：高血压 3级、极高危,处方2阿司匹林100 mg 一天一次，替米沙坦80 mg 一天一次,氢氯噻嗪12.5 mg一天一次，尼群地平片10 mg 一天两次,处方2 2周后血压平稳在130-120/80-70 mmHg 范围，并随访1年至今平稳。同时配合
30、低盐、低糖和低脂饮食，减体重及运动等生活方式改善，血糖5.5 mmol/L，尿常规蛋白（-）,感觉及精神状态较以前明显变好。,处方2分析：（1）因该患者为高危病人，故应用证据较多、耐受性较好的替米沙坦，它既属长效的ARB类药物、又可减轻左心室肥厚、保护心、肾功能和减少蛋白尿，改善糖代谢等。（2）加用小剂量氢氯噻嗪以协同替米沙坦的降压作用。,处方2分析：（3）因该患者血压难控制，故合用尼群地平片，三联用药。（4）合用阿司匹林以协同预防心脑血管病的发生或发展。（5）降压治疗达标的同时，还应使血脂、血糖、体重、生活方式等指标也达到理想水平。,处方3患者女性，75岁，干部。高血压近20年，最高220/
31、100 mmHg，就诊时正在服用复方罗布麻片2片，一天2次；,处方3同时合并冠心病稳定性心绞痛（劳力+自发型），冠脉造影：近中段LAD70%节段性狭窄，LCX远端50%狭窄，运动核素心肌显像正常；就诊血压170/96 mmHg，心率84次/分；LDL-C 3.4 mmol/L,血糖正常。,处方3诊断：冠心病心绞痛（劳力+自发型），高血压3级、极高危，血脂异常,处方3阿司匹林100 mg 一天1次，阿托伐他汀10mg每晚1次；卡托普利25 mg 一天2次,氨氯地平5 mg 一天1次,美托洛尔25mg一天2次，二硝酸异山梨醇酯15mg一天3次；,处方32周后血压平稳138/80 mmHg，心率60
32、次/分，血清LDL-C 2.4 mmol/L。但出现干咳，以夜间为著，且血尿酸轻度升高（460umol/L）,处方3氯沙坦50mg一天1次取代卡托普利。同时生活方式改善。随访1年病情至今平稳，血压（130/80 mmHg）、尿酸（402umol/L）及血脂（LDL-C 2.2 mmol/L）均达标。,处方3分析：（1）降血压时，体现冠心病“ABC”二级预防方案：A：阿司匹林及ACEI/ARB；B：阻滞剂；C：他汀类药物。,处方3分析：（2）一药多效：阻滞剂和氨氯地平：既是肯定的抗高血压一线药物，又分别是劳力和自发型心绞痛的抗心肌缺血的有效用药；两药合用使其疗效叠加、不良反应相互抵消。,处方3分
33、析：（3）ACEI明显咳嗽时，可用ARB替代之，氯沙坦同时降低血压和尿酸，个性化配伍，艺术用药。（4）与时俱进，动态中保持最合适的方案，选好主药、兼顾辅药、加加减减、科学调药。,合理用药体会（1）落实指南，把握方向，针对性强，具体的病人具体分析，全面评估血压变化、合并疾病及其危险因素、用药情况等，科学决策、制定出合理的用药方案，并长期坚持之。,合理用药体会（2）治疗程度与病情轻重相匹配，高危强化降压，如冠心病等危症160/100 mmHg，应该2药或多药小剂量合用，尽快达标，摸索、维持方案。,合理用药体会（3）提高达标，若无禁忌，尽量合用小剂量利尿剂。（4）24小时血压平稳到理想水平。不但血压达标，而且有效保护靶器官结构和功能。,合理用药体会（5）合理配伍，取长补短，正作用协同相加，副作用相互抵消。（6）治疗高血压，同时全面控制心血管病的多重危险因素。,合理用药体会（7）牢记4个目标：（a）血压水平达标;（b）保护心脑肾等靶器官；（c）最高目标为防治心脑血管病，延年益寿；（d）注重提高生活质量！,谢谢,
