高血壓合理用藥要點討論及處方

1、高血壓合理用藥最新要點討論及處方分析,,我國高血壓患病率愈來愈高,,全國患病人數(shù)已超過2.0億,中國居民營養(yǎng)與健康現(xiàn)狀調(diào)查。衛(wèi)生部、科技部、統(tǒng)計局，2019、10、12,,我國18歲及以上居民高血壓患病率為18.8%,中國高血壓控制率,降壓本身的益處,平均降低 卒中發(fā)生率 35–40% 心肌梗死

2、 20–25% 心力衰竭 50%,,,,,JNC 7,收縮壓降低10–12mmHg或舒張壓降低5-6mmHg,1、高血壓治療四大目標,長期、有效、平穩(wěn)控制血壓水平預(yù)防(逆轉(zhuǎn))心、腦、腎等靶器官的損害減少心、腦血管疾病的發(fā)病和死亡——循證醫(yī)學(xué)改善生活質(zhì)量,亞臨床靶器官損害之保護 (2009,oct ESH Reappraisal)Evid

3、ence 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 pla

4、que or thickening, an increased arterial stiffness, a reduced eGFR (assessed by the MDRD formula), or microalbuminuria or proteinuria substantially increases the total cardiovascular risk, usually moving hypertensive pat

5、ients into the high absolute risk range.合并亞臨床靶器官損害常為高危者：LVH,頸動脈斑塊、增厚硬化， eGFR下降，微量/蛋白尿。----Journal of Hypertension 2009, 27:2121–2158,血壓目標 所有患者 <140/90 <140/90DM/腎病 <130/80(DM)

6、 <130/80冠心?。?30/80 mm Hg (2019/2009年歐洲高血壓指南)*老年SBP難于140可適當靈活些(尤低危者)，老年收縮壓可降至150 mm Hg以下,血壓目標 ——低限？ (ESH June, 2009 )Key among the changes will be the recommendation of a lower threshold level--around 120 mm H

7、g 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

8、for High-Risk Individuals “J形曲線”可能存在，有些特定高?；颊哐獕翰灰诉^低（<120/70）----June 16, 2009 (Milan, Italy) — The European Society of Hypertension (ESH),血壓達標 (2009,oct ESH Reappraisal) Each drug class has contraindications as

9、 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 aver

10、age patient as reference, has now little scientific and practical justificationand should be avoided.每種藥物均有利弊：應(yīng)循證選藥；強調(diào)個性化用藥，避免一線、二線、三線----Journal of Hypertension 2009, 27:2121–2158,何時開始用藥 (2009,oct ESH Reappraisal)

11、it appears reasonable to recommend that, in grade 1 hypertensives (SBP 140–159mmHg or DPB 90–99mmHg) at low and moderate risk, drug therapy should be started after asuitable period with lifestyle changes. Prompter initi

12、ation of treatment is advisable if grade 1 hypertension is associated with a high level of risk, or if hypertension is grade 2 or 3. 立即用藥：a）2或3級高血壓; b）1級HT +高危改善生活方式后用藥：1級HT +低、中危,2、治療策略（中國）幾周內(nèi)漸降血壓至目標, 更長/更短期間？（

13、幾天？）推薦長效劑，持續(xù)24小時、T/P>50%， Qd，提高順從、平穩(wěn)降壓據(jù)血壓水平、RF、TOD、ACC,選單或多藥聯(lián)合制定個性化方案：2級以上高血壓常需聯(lián)合用藥，配合非藥物療法,達標快慢： (2009, June ESH)"In 2019, we took a strong stance in favor of combination treatment. This has been shown

14、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 catastrophe," and more recently, studies have

15、 shown there is less discontinuation of treatment in this patient population if treatment is started with combination therapy, Mancia said.對高?；颊吒鼉A向于：聯(lián)合用藥、盡快達標、預(yù)防事件----June 16, 2009 (Milan, Italy) — The European Societ

16、y of Hypertension (ESH),3、藥物治療戰(zhàn)略理念,3-1用藥模式：1）套餐模式：1950—60s2）席餐模式: 1970—80s3）自助餐模式: 1990—2000s,3-2常用五類藥物及其配方：RAS拮抗劑：ACEI(普利) ARB(沙坦)鈣拮抗劑： CCB(地平等)利尿劑 (噻嗪等)Beta阻滯劑： BB(洛爾

17、等),2009 ESC/ESH 專家意見,,利尿劑,CCB,ARB,ACEI,3-3 2019ESC/ESH指南推薦聯(lián)合: ①噻嗪類利尿劑與ACEI，②噻嗪類利尿劑與ARB，③鈣拮抗劑與ACEI，④鈣拮抗劑與ARB，⑤鈣拮抗劑與噻嗪類利尿劑，⑥β- 受體阻滯劑與二氫吡啶類鈣拮抗劑。,保護心腦腎作用突出： (2009,oct ESH)In no less than 15–20% of hypertensive pat

18、ients, 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

19、at effective doses.至少15–20% 高血壓患者，需要三聯(lián)用藥：最合理方案：RAS拮抗劑+CCB+利尿劑----Journal of Hypertension 2009, 27:2121–2158,合理聯(lián)合用藥方案： (2009,oct ESH) The combination of two antihypertensive drugs may offer advantages also for tre

20、atment 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 should be preferred, because simp

21、lification of treatment carries advantages for compliance to treatment.在高危病人，兩藥聯(lián)合還可盡快達標應(yīng)優(yōu)先應(yīng)用固定劑量的單片劑復(fù)方：使治療簡化、順應(yīng)性提高,4-2、2019歐洲高血壓指南: 長效鈣通道阻滯劑：沒有強制禁忌證。推薦用于:腦卒中、老年單純收縮期高血壓、心絞痛、左室肥厚、頸動脈或冠狀動脈粥樣硬化、妊娠婦女、黑人高血壓等。,ACE

22、I/ARB類藥物的絕對禁忌證,妊娠　血管神經(jīng)性水腫　高鉀血癥　雙側(cè)腎動脈狹窄,4-2、2019歐洲高血壓指南: ACEI ：ACEI優(yōu)先適應(yīng)證共10項：心力衰竭、左室肥厚、左室功能異常、心肌梗死后、糖尿病腎病、非糖尿病腎病、頸動脈粥樣硬化、蛋白尿或微量蛋白尿、心房顫動和 代謝綜合征等,4-2、2019歐洲高血壓指南: ARB優(yōu)先適應(yīng)證：1.老年患者2.糖尿病3.腎功能不全4.腦卒中5.冠心病和心衰6

23、.房顫7.代謝綜合征,Beta阻滯劑： (2009, June ESH)The totality of evidence now shows different conclusions for different patient populations, he said. "For example, for stroke prevention, beta blockers are inferior to calcium a

24、ntagonists, but for congestive heart failure prevention, beta blockers are superior to calcium antagonists and similar to other drugs," 對腦卒中預(yù)防，BB弱于CCB; 對心衰， BB強于CCB----June 16, 2009 (Milan, Italy) — The Europea

25、n Society of Hypertension (ESH),Beta阻滯劑： (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 stro

26、ke (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 efficacy than other drugs in patients with arecent coron

27、ary event 目前最大（n=147）RCT薈萃分析示：與其他藥物比，Beta阻滯劑，預(yù)防腦卒中方面略弱；預(yù)防冠脈事件和心衰，相同；預(yù)防近期冠脈事件，較好。,RAS拮抗劑： (2009,oct ESH) ONTARGET has shown telmisartan not to be statistically inferior to ramipril as far as the incidence of a

28、 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 conclu

29、sion that ACE inhibitors and angiotensin receptor antagonists have the same preventiveeffect on myocardial infarction ONTARGET示：預(yù)防冠脈事件和預(yù)防腦卒中 方面，替米沙坦與雷米普利相同； 最近薈萃分析示：預(yù)防心梗療效，ARB與ACEI相同。,個性化選藥： (2009, June ESH)

30、"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 whic

31、h drug might be preferred in 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."最好用藥模式：在合適的情況，選擇合適

32、的藥物，用于合適的病人；----June 16, 2009 (Milan, Italy) — The European Society of Hypertension (ESH),老年高血壓： (2009, Oct ESH)At variance from previous guidelines, evidence is now available from an outcome trial (HYVET) that antihy

33、pertensive 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

34、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歲或以上的老年高血壓降壓也可獲益；常常一種藥開始，如需要再加另一種；小心謹慎、個性化。,糖尿病高血壓： (20

35、09, Oct ESH) In diabetes, combination treatment is commonly needed to effectively lower BP. A renin–angiotensin receptorblocker should always be included because of the evidence of its superior protective effect aga

36、inst initiation orprogression of nephropathy.糖尿病合并高血壓常需聯(lián)合降壓；其中ARB因其優(yōu)質(zhì)的腎保護作用，不應(yīng)缺少；,降壓作用：85-90%降壓外作用：15-10%降壓外作用依賴降壓作用降壓療效依賴：1）降壓幅度、基線血壓、危險程度、并發(fā) 癥及合并癥，降壓對象等。2）合適的藥物：品種、劑量、用法、時程 、配伍，等。,降壓達標是關(guān)鍵，全面防

37、治為根本,CAD 預(yù)防: <140/90 任何有效抗高血壓藥物或聯(lián)合CAD高危者: <130/80 ACEI 或 ARB 或CCB或噻嗪利尿劑或聯(lián)合穩(wěn)定性心絞痛: <130/80 ß-Blocker 和ACEI 或 ARBUA/NSTEMI: <130/80 ß-Blocker (若血動學(xué)穩(wěn)定) 和 ACEI 或 ARBSTEMI: <130/80 ß-Bloc

38、ker (若血動學(xué)穩(wěn)定) 和 ACEI 或 ARBLVD: <120/80 ACEI 或ARB 和 ß-blocker 和 醛固酮拮抗劑 和噻嗪 或 袢利尿劑 和 hydralazine /亞硝酸異山梨酯 (黑種人),指南推薦匯總: BP 目標 mm Hg :--AHA Scientific Statement 2019: Hypertension in Ischemic Heart Disease,處方1患者男，

39、42歲，農(nóng)民，高血壓10余年，最高220/120 mmHg, 無明顯癥狀，未規(guī)律用藥，否認其他病史，吸煙20年（20支/日），父親有高血壓腦出血病史。,處方1就診查體：血壓180/112 mmHg。心電圖：左心室高電壓，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年內(nèi)無明顯動態(tài)性改變。心臟超聲：左心室舒張功能減退，LA38 mm, IVS 13 mm, PW 11 mm, 符合高血壓左心

40、室肥厚改變。尿常規(guī)（-）。血脂血糖均在正常范圍內(nèi)。,處方1診斷：高血壓 3級、高危,處方1：卡托普利（國產(chǎn)）25 mg Tid; 雙氫克尿噻 25 mg Qd, 1周后12.5 mg Qd; 尼群地平（國產(chǎn)）10 mg Tid；1周后加用阿司匹林100 mg Qd。,1周時復(fù)測血壓110/70 mmHg，病人有時從平臥突然站立時感覺頭昏不適,處方1：將尼群地平改為5 mg Bid，幾天后頭昏不適的癥狀消失，

41、血壓132/84 mmHg。,處方1：待2周后尼群地平10 mg Bid，余藥同前，患者無不適癥狀，血壓114/70 mmHg，維持長期治療。1年后將卡托普利改為25 mg Bid, 余藥同前。每天治療費用1角左右，血壓2年來一直維持于100-110/60-70 mmHg之間，無任何不適。,處方1：分析：（1）因該患者為中年男性、3級高危高血壓，合并左心室肥厚、吸煙等危險因素，故降壓目標應(yīng)該<120/80 mmHg。（

42、2）開始用藥時，曾因不適應(yīng)，一度頭昏不適，待治療一段時間后大多數(shù)病人會逐漸適應(yīng)的，可據(jù)具體情況隨時調(diào)整用藥。（3）目前，ACEI類藥物的強適應(yīng)癥最多，故本方主藥為卡托普利，最佳配角為雙氫克尿噻，兩者合用效果可翻倍。,處方1：分析：（4）因患者年輕、血壓太高、病程長、未規(guī)律用藥，故加尼群地平，以盡快達標、提高順從性；如果年齡較大、非高危，用藥及加量不必像本方那樣“強烈”。（5）該患者達標后，長期維持摸索好的方案，少花錢多獲效益。

43、,處方2患者男性，51歲，外企職員。發(fā)現(xiàn)高血壓5年，最高血壓180/120 mmHg，就診時正在服用復(fù)方降壓片2片，一天三次； 血壓忽高忽低，在160-150/100-90 mmHg范圍；,處方2心臟超聲示左心室肥厚: IVS及PW均為13 mm， 空腹血糖6.3 mmol/L，尿常規(guī)蛋白（+），吸煙20年，20支/日。,處方2診斷：高血壓 3級、極高危,處方2阿司匹林100 mg 一天一次，替米沙坦80

44、mg 一天一次, 氫氯噻嗪12.5 mg一天一次，尼群地平片10 mg 一天兩次,,處方2 2周后血壓平穩(wěn)在130-120/80-70 mmHg 范圍，并隨訪1年至今平穩(wěn)。同時配合低鹽、低糖和低脂飲食，減體重及運動等生活方式改善，血糖5.5 mmol/L，尿常規(guī)蛋白（-）,感覺及精神狀態(tài)較以前明顯變好。,處方2分析：（1）因該患者為高危病人，故應(yīng)用證據(jù)較多、耐受性較好的替米沙坦，它既屬長效的ARB類藥物、又可減輕左心室肥

45、厚、保護心、腎功能和減少蛋白尿，改善糖代謝等。（2）加用小劑量氫氯噻嗪以協(xié)同替米沙坦的降壓作用。,處方2分析：（3）因該患者血壓難控制，故合用尼群地平片，三聯(lián)用藥。（4）合用阿司匹林以協(xié)同預(yù)防心腦血管病的發(fā)生或發(fā)展。（5）降壓治療達標的同時，還應(yīng)使血脂、血糖、體重、生活方式等指標也達到理想水平。,處方3患者女性，75歲，干部。高血壓近20年，最高220/100 mmHg，就診時正在服用復(fù)方羅布麻片2片，一天2次；,處方3

46、同時合并冠心病穩(wěn)定性心絞痛（勞力+自發(fā)型），冠脈造影：近中段LAD70%節(jié)段性狹窄，LCX遠端50%狹窄，運動核素心肌顯像正常；就診血壓170/96 mmHg，心率84次/分；LDL-C 3.4 mmol/L, 血糖正常。,處方3診斷：冠心病心絞痛（勞力+自發(fā)型），高血壓3級、極高危，血脂異常,處方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

47、一天1次, 美托洛爾25mg一天2次，二硝酸異山梨醇酯15mg一天3次；,處方32周后血壓平穩(wěn)138/80 mmHg，心率60次/分，血清LDL-C 2.4 mmol/L。但出現(xiàn)干咳，以夜間為著，且血尿酸輕度升高（460umol/L）,處方3氯沙坦50mg一天1次取代卡托普利。同時生活方式改善。隨訪1年病情至今平穩(wěn)，血壓（130/80 mmHg）、尿酸（402umol/L）及血脂（LDL-C 2.2 mmol/L

48、）均達標。,處方3分析：（1）降血壓時，體現(xiàn)冠心病“ABC”二級預(yù)防方案：A：阿司匹林及ACEI /ARB；B：β阻滯劑；C：他汀類藥物。,處方3分析：（2）一藥多效：β阻滯劑和氨氯地平：既是肯定的抗高血壓一線藥物，又分別是勞力和自發(fā)型心絞痛的抗心肌缺血的有效用藥；兩藥合用使其療效疊加、不良反應(yīng)相互抵消。,處方3分析：（3）ACEI明顯咳嗽時，可用ARB替代之，氯沙坦同時降低血壓和尿酸，個性化配伍，藝術(shù)用藥。

49、（4）與時俱進，動態(tài)中保持最合適的方案，選好主藥、兼顧輔藥、加加減減、科學(xué)調(diào)藥。,合理用藥體會（1）落實指南，把握方向，針對性強，具體的病人具體分析，全面評估血壓變化、合并疾病及其危險因素、用藥情況等，科學(xué)決策、制定出合理的用藥方案，并長期堅持之。,合理用藥體會（2） 治療程度與病情輕重相匹配，高危強化降壓，如冠心病等危癥160/100 mmHg，應(yīng)該2藥或多藥小劑量合用，盡快達標，摸索、維持方案。,合理用藥體會（3）提