高血壓治療新趨勢 - tainanhealth.org.t · Topics •高血壓之控制率 •高血壓用藥之選擇 •Fix-Dose Combination之優勢 •血壓藥之發展趨勢

高血壓治療新趨勢

Name: 黃文伸Date: 97.06.27

Topics

• 高血壓之控制率

• 高血壓用藥之選擇

• Fix-Dose Combination之優勢

• 血壓藥之發展趨勢

Topics





三高 (代謝症候群)

難分難解的三角習題

血壓與相關疾病的關聯

血壓持續升高冠狀動脈心臟病

左心室肥大

心臟衰竭

腦出血

動脈硬化

末期腎病變

Definition of Metabolic Syndrome in Taiwan

2007-01-18

修正前（臺灣2004年版）修正後（臺灣2006年版）

危險因子異常值危險因子異常值

腹部肥胖(Central obesity) /或身體質

量指數（BMI）

腰圍（waist）:男性 ≧90 cm 女性 ≧80 cm ；或

BMI ≧27

腹部肥胖(Central obesity)

腰圍（waist）:男性 ≧90 cm女性 ≧80 cm

血壓(BP)上升SBP ≧130 mmHg /DBP ≧85 mmHg

血壓(BP)上升SBP ≧130 mmHg /DBP ≧85 mmHg

高密度酯蛋白膽固

醇(HDL-C)過低

男性 <40 mg/dl女性 <50 mg/dl

高密度酯蛋白膽

固醇(HDL-C)過低

男性 <40 mg/dl；女性

<50 mg/dl

空腹血糖值(Fasting glucose)上升

FG ≧110 mg/dl空腹血糖值

(Fasting glucose)上升

FG ≧100 mg/dl

三酸甘油酯

(Triglyceride)上升TG ≧150 mg/dl

三酸甘油酯

(Triglyceride)上升TG ≧150 mg/dl

http://www.bhp.doh.gov.tw

1177-SL-08-01

8

ESH/ESC and JSH

Optimal BP

Normal BP

High normal BP

Grade 1 hypertension

(mild)


(moderate)


(severe)

SBP and DBP

<120 and <80

120-9 or 80-4

130-9 or 85-9

140-59 or 90-9

160-79 or 100-9

>180 or >110

理想的血壓應控制在SBP<120 and DBP<80

JNC 7

Normal

Prehypertension

Stage 1 hypertension

Stage 2 Hypertension

只有30%血壓病患達治療目標

1. Top 7 countries world-wide

2. Goal defined as 140/90

% of patients not diagnosed

% of patients

% of diagnosed not treated

% of treated not at goal2

% treated optimally

45

42

70

9

181 million hypertensives WW1

81

42

41

6

No. of Patients

(Mio.)

10

USA

34.0

Canada

16.0

Australia

7.0

Finland

20.5Scotland

17.5 Germany

22.5

Spain

15.5

France

27.0

England

6.0

India

9.0Zaire

2.5 Italy

23.4

臺灣高血壓的控制率

JNC 7. JAMA. 2003;289:2560 ; Le W. et al. J Hypertens. 2003;21:1191 ; Burt VL. Hypertension. 1995;26:60 ; Mancia G.

Eur Heart J. 1999;(suppl L):L14 ; 衛生署國民健康局: 九十一年台灣地區高血糖、高血脂、高血壓盛行率調查 ;

*National Health Bureau, Taiwan 2003 (Target; BP< 140/90 mmHg)

Taiwan

24.3

China

33.0

Male: 20.8 %

*

Female:

28.5%

11

血壓越高,罹患心血管疾病的風險越高

*Individuals aged 40–69 years, starting BP 115/75 mmHg

Chobanian et al. JAMA 2003;289:2560–72

CV

mo

rtal

ity

risk

SBP/DBP (mmHg)

0

1

2

3

4

5

6

7

8

115/75 135/85 155/95 175/105

2x

4x

8x

Benefit of Lowering BP

20%~25%

MI35%~40%

Stroke

>50%

HF

0

The Seventh Report of the Joint National Committee on Prevention, Detection,

Evaluation, and Treatment of High Blood Pressure. JAMA. 2003;289:2560-2572

SBP Distributions

Before

Intervention

Reduction in SBP

mmHg

% Reduction in Mortality

Reduce

BP

After

Intervention

2 -6 -4 -3

3 -8 -5 -4

5 -14 -9 -7

Population-Based Strategy

Stroke CHD Total

5 3 2 0

Hypertension. 2003;42:1206–1252.

Topics





Selection of Anti-Hypertensive

Agents

Effective – lowering BP efficacy

Compelling indication

2003 WHO/ISH Guideline

2003 ESH/ESC Guideline

2003 JNC 7 Guideline

高血壓治療的發展

Diuretics

Beta-Blockers

Ca++ Channel Blockers

ACE Inhibitors

Angiotensin II Receptor Blockers

( ARB )

JNC VII: Management of Hypertension

by Blood Pressure Classification

Drug(s) for the compelling

indications; other

antihypertensive drugs

(diuretics, ACE-I, ARB, BB,

CCB) as needed

Drug(s) for the

compelling indications;

other antihypertensive

drugs (diuretics, ACE-I,

ARB, BB, CCB) as

needed

BP Classification

Lifestyle

Modification

Initial Drug Therapy

Without Compelling

Indication

With Compelling

Indication

Normal

<120/80 mm Hg

Prehypertension

120-139/80-89 mm

Hg


140-159/90-99 mm Hg


160/100 mm Hg

Encourage

Yes

Yes

Yes

No drug indicated Drug(s) for the

compelling indications

Thiazide-type diuretics

for most; may consider

ACE-I, ARB, BB, CCB,

or combination

2-drug combination for most

(usually thiazide-type diuretic

and ACE-I, ARB, BB, or

CCB)

Topics





AASK MAP <92

Target BP

(mm Hg)

Average No. of Antihypertensive Agents

1

UKPDS DBP <85

ABCD DBP <75

MDRD MAP <92

HOT DBP <80

Trial 2 3 4

IDNT SBP/DBP 135/85

Multiple Antihypertensive Agents Are Needed to Achieve Target BP

UKPDS = United Kingdom Prospective Diabetes Study; ABCD = Appropriate Blood Pressure Control in

Diabetes; MDRD = Modification of Diet in Renal Disease; HOT = Hypertension Optimal Treatment; AASK =

African American Intervention Study of Kidney Disease; IDNT = Irbesartan Diabetic Nephropathy Trial.

Bakris GL et al. Am J Kidney Dis. 2000;36:646-661. Lewis EJ et al. N Engl J Med. 2001;345:851-860.

ESH 2007: Possible Combinations of Different Classes of Antihypertensive Agents

ESH Guidelines. J Hypertens. 2007;25:1105-1187;

Co-DIOVAN®

(Valsartan 80mg +12.5mg

HCTZ)

BP Effect Adverse Effect

Law MR,BMJ, 2004

Fall in SBP (mmHg)

Drug Category ½ x dose Standard dose 2 x dose

Thiazide 7.4 8.8 10.3

B blocker 7.4 9.2 11.1

ACEI 6.9 8.5 10.0

ARB 7.8 10.3 12.3

CCB 5.9 8.8 11.7

Average 7.1 9.1 10.9

Law MR, et al. BMJ 2003;326:1427

SBP Reduction by Drug and Dose

Low-dose thiazide has effective in BP control with lower side effect

Law MR, et al. BMJ 2003;326:1427

Percentage with symptoms

Drug category No of trials ½ xdose Standard 2xdose

Thiazides 59 2.0 9.9 17.8

B blockers 62 5.5 7.5 9.4

ACEI 96 3.9 3.9 3.9

ARB 44 -1.8 0 1.9

CCB 96 1.6 8.3 14.9

Adverse Effects by Drug and Dose

1顆Co-Diovan相當於 2顆 Amlodipine的療效且具有較佳的耐受性

Palatini P et al. J Hypertens. 2001;19:1691-1696.

4 Weeks 12 Weeks

-30

-25

-20

-15

-10

-5

0

Diastolic Systolic Diastolic Systolic

Mean

Reduction

in Blood

Pressure

(mm Hg)

Valsartan 80 mg ± 12.5 mg HCTZ

Amlodipine 5-10 mg

Valsartan 80 mg

Amlodipine 5 mg

Incidence of treatment-related adverse events was 5.5% for the amlodipine vs

1.5% for the valsartan group (P = 0.006)

ESH 2007: Possible Combinations of Different Classes of Antihypertensive Agents

ESH Guidelines. J Hypertens. 2007;25:1105-1187;

0

2

4

6

8

10

12

14

16

2.4

0

3.6

14.3

Diovan 80mg

(n=84)

Diovan 80mg +

Amlodipine 5mg

(n=24)

Amlodipine 5mg

(n=24)

Amlodipine 10 mg

(n=24)

% o

f p

ati

en

ts w

ith

ed

em

aTolerability

Diovan發生水腫的比例低

•Clin Pharmacol Therap 1996; (60:341-346)

蘋果日報新聞稿

Exforge(易安穩)的正面評價報導

同時有兩藥優點-台北榮民總醫院老年醫學科主任陳亮恭表示，「得安穩」預防心衰竭、糖尿病、腎病變等風險顯著，「脈優」降血壓效果穩定，預防中風效果強，「新藥可同時有兩種藥物優點。」-台大醫院心臟內科主任曾春典表示，國內高血壓病患約有兩百萬人，許多患者每天要同時吃「脈優」與「得安穩」，若是改為只吃一顆，可以便利患者控制血壓。

AT1 receptor-mediated constriction: Efferent arterioles > Afferent eaarterioles

Glomerular hyperfiltration & Intraglomerular pressure

Glomerular barrier dysfunction Proteinuria Excessive tubular reabsorption of

protein Tubulointerstitial fibrosis Am J Physiol 1992; 262; F367

Ang II

http://www.hypertensiononline.org/slides2/slide01.cfm?tk=2&pg=2

S

M A

R T

Microalbuminuria Reduction with Intensive

Antihypertensive Treatment by Renin-Angiotensin System-

Blocking or Calcium Channel-Blocking in Hypertensive

Patients with Type 2 Diabetes Mellitus

Shiga MicroAlbumiuria Reduction Trial (SMART) group

Atsunori Kasiwagi, MD, PhD

Professor of Endocrinology and

Metabolism Division,

Shiga University of Medical Science

Change in Urinary Albumin Level

-36

21

-50

-40

-30

-20

-10

0

10

20

30

40(m

g/g

･ Cr)

p=0.00000

AMLVAL

Journal of Hypertension 2007, Vol 25 No 9

Albuminuria response to very

high-dose valsartan in type 2

diabetes mellitus

Placebo

Run-In

Diovan 160mg

Week 4

(Visit 8)

Week 0

(Visit 6)

(Randomization)

Diovan 640mg

Diovan 320mg

Diovan 160mg

Week 30

(Visit 12)

Screening

Week -3

(Visit 3)

Week -6

(Visit 1)

Week -2

(Visit 4)

Diovan 160mg

Diovan 160mg

Week 16

(Visit 11)

N=370 type II hypertensive, microalbuminuric (30-1000 mg/d) diabetic patients

N=50 sites, primarily in U.S.


Est

imat

ed c

han

ge

in

UA

ER

at

wee

k 30

(%

)

Valsartan 160 mg

Valsartan 320 mg

Valsartan 640 mg

0

–10

–20

–30

–40

–50

–60

1Observed cases methodology (ITT1 population) was used

*P<0.001 vs. Baseline†P=0.125 vs.160 mg

*

** †

Linear trend (slope): –0.0004 (P=0.141)

DROP: Change from Baseline in Urinary Albumin Excretion Rate – ITT Population


固定複方可提高病患順從度

FDCFree

Combo

80.8% 73.9%

1 Taylor, A., Congestive Heart Failure, Nov./Dec. 2003, 2 NDC Dataset

FDCFree

Combo

55% 45%

In studies1… And in practice2…

Lotrel vs ACE+CCB2 ARB+HCT

Patients Continuing on therapy after 12 months

Decreasing pill burden increases persistence

Increased adherence drives better outcomes and lower hospitalization risk

1. Sokol, Michael; “Impact of Medication Adherence on Hospitalization Risk and Healthcare Cost” – Medical Care June 2005 pp 521-530

Hospitalization risk (%)

Compliance rate

137,000 Patient Study

病患遵醫囑性越高住院風險越低

Source: IMS NPA Dec 2004

固定複方治療方式日漸受到歡迎

TRx MQT Y-o-Y Growth Rates (%)

2006, July 28

BHS / NICE

Topics





Higher Persistency Rates With ARBs vs Other Antihypertensive Therapy

67.4

Per

sist

ence

(%

)

ARBs ACE

inhibitors

Calcium

Channel

blockers

Beta-blockers Thiazide

diuretic

†

60.7

50.946.5

16.4

*34.7

*40.7

20.8

†

54.1 †

45.6

1 year 4 years

*p<0.03 vs ARBs; †p<0.01 vs ARBs

Treatment persistence from 12 to 48 months was greater with ARBs than with

other antihypertensives (p<0.001)

Conlin P et al. Clin Ther 2001;23:1999–2010

*

VALIENT

LIFE Study

Drugs for Renin−Angiotensin−Aldosterone System

N Engl J Med 2008 June 5;358:2503-5

FDA approves aliskiren: First new antihypertensive on the market in more than 10 years

March 6, 2007

Michael O'Riordan

Basel, Switzerland - The Food and Drug Administration (FDA) has approved the blood-pressure drug aliskiren (Tekturna, Novartis), the first new antihypertensive medication to be approved in more than 10 years.

The drug is the first in a new class of agents known as oral renin inhibitors and is approved for the treatment of high blood pressure as monotherapy or in combination with other antihypertensive medications. The drug is expected to be available in pharmacies this month in 150-mg and 300-mg doses.

A once-daily oral tablet, aliskiren blocks the action of renin at the top of the renin-angiotensin-system cascade. A pooled data analysis of antihypertensive treatment with the drug in more than 8000 patients, presented by Dr Matthew R Weir (University of Maryland School of Medicine, Baltimore) at the World Congress of Cardiology in Barcelona in September and previously reported by heartwire, suggested that it reduces blood pressure effectively regardless of age or gender, is well tolerated, and appears to be additive to most other antihypertensive agents, with the exception of angiotensin-receptor blockers.

In December, the FDA extended by three months its review of aliskiren following the voluntary submission of more data by Novartis. Preclinical work in rats showed some irritation of the colonic mucosa with the drug, so a decision was made to do a further study in 30 healthy volunteers. Results of this showed no changes in the mucosal lining of the colon, Novartis said.

Financial analysts have previously suggested that aliskiren may generate sales of at least $1 billion a year.

http://www.theheart.org/viewAuthorBio.do?primaryKey=114633

Rasilez NEJM Update

Reduce ACR / UAER

Beyond BP Lowing Effect

Drugs for Renin−Angiotensin−Aldosterone System

N Engl J Med 2008 June 5;358:2503-5

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高血壓治療新趨勢 - tainanhealth.org.t · Topics •高血壓之控制率 •高血壓用藥之選擇 •Fix-Dose Combination之優勢 •血壓藥之發展趨勢