한국인의 혈압 조절 및 혈관 건강 유지를 위해 어떤 약물이 효과적인가?

Park Sungha

Yonsei University College of Medicine

Cardiovascular Center

Division of Cardiology

한국인 고혈압의 특징은 무엇이며 어떤 약물을 사용하는 것이

효과적일까?

Stroke and MI in

Hypertension Trials1-3

1. Kjeldsen SE et al. Blood Pressure 2001;10:190-192. 2. Dahlöf B et al. Lancet 2002;359:995-1003. 3. Wing LMH et al.

N Engl J Med 2003;348:583-592.

3

0

1

2

3

4

5

6

7

8

Pe

rce

nta

ge o

f p

ati

en

ts w

ith

eve

nt Stroke

Myocardial Infarction

Percentage of fatal and nonfatal strokes, and fatal and nonfatal MIs reported in large,

prospective hypertension trials published after 1990.

Hypertension and CVD Deaths in

Asia-Pacific Region

Its prevalence and population-attributable fraction for mortality from cardiovascular

disease in the Asia-Pacific region

Hypertension

Ischemic heart disease

Hemorrhagic stroke

Ischemic stroke

0

Fiji

Bangladesh

Indonesia

Singapore

Taiwan

Thailand

Philippines

China

Hong Kong

South Korea

Australia

New Zealand

Malaysia

Japan

Mongolia

20 40 60 Population-attributable fraction (%)

80

Men

0 20 40 60 Population-attributable fraction (%)

80

Women

Martiniuk ALC, et al. J Hypertens. 2007;25:73–79.

CVD: cardiovascular disease

Ischemic Heart

Disease 20-25%

Hemorrhagic

Stroke 40-50%

Ischemic

Stroke 30-40%

4

Hypertension prevalence: fraction of people 30 years or over with systolic blood pressure

≥140 mmHg or diastolic blood pressure ≥90 mmHg or medication history of

antihypertensive drug

100

0

80

40

’98

20

60

(%)

’01 ’05 ’07 ’08 ’09 ’10 ’11

32.5

26.9

33.2

25.4

31.5

23.9

26.9

21.8

28.1

23.9

29.3

23.9

32.9

23.7

30.4

22.2

Male

Female

100

0

80

40

20

60

(%)

14.6

Female Male

31.2 38.0

53.5 58.9

3.4

10.8

29.7

57.1

71.5

Korean National Health and Nutrition Survey 2011.

30- 39

40- 49

50- 59

60- 69

70+ 30- 39

40- 49

50- 59

60- 69

70+

Trend of hypertension

prevalence

Age-specific prevalence of

hypertension

Awareness rate: Ratio of being diagnosed with hypertension among hypertension patients

Treatment rate: Ratio of current antihypertensive administration among hypertension patients

Control rate: Ratio of systolic blood pressure <140 mmHg or diastolic blood pressure < 90 mmHg among hypertension patients

100

0

80

30

1998

10

50

(%)

58.5

Male (age ≥30)

20

40

90

70

60

2001 2005 2011 year

Treatment rate Control rate Awareness rate

51.7

36.9

100

0

80

30

1998

10

50

(%)

Female (age ≥30)

20

40

90

70

60

2001 2005 2011 year

76.1 71.3

49.4

Korean National Health and Nutrition Survey 2011.

Trend of hypertension

management

6

한국인에서 고혈압의 특징

염분섭취가 서양에 비해 높다 이뇨제와 CCB가 효과적일 가능성

뇌졸중이 보다 더 흔한 합병증이고 고혈압의 population attributable fraction은

뇌졸중과 더 강하게 연관되어 있다

CCB가 효과적일 가능성

Law MR et al. BMJ 2009;338;1665

Fatal and non-fatal stroke

Number at risk

Amlodipine besylate 9639 9483 9331 9156 8972 7863

perindopril Atenolol thiazide 9618 9461 9274 9059 8843 7720

0.0 1.0 2.0 3.0 4.0 5.0 Years 0.0

1.0

2.0

3.0

4.0

5.0

Amlodipine besylate perindopril

(No. of events 327)

Atenolol thiazide

(No. of events 422)

HR = 0.77 (0.660.89)

p = 0.0003

%

Dahlö f B et al. Lancet 2005;366:895-906

ACCOMPLISH

K.Jamerson et al: N Engl J Med 2008;359:2417-2428

Blood Pressure Trend

1st Evaluation Item (Cardiovascular Death and the Symptom Occurrence of a Cardiovascular Event)

Relative Risk Reduction Rate 20%

(Hazard Rate 0.80;95% CI , 0.72 to 0.90; P <0.001).

16 14 12 10 8 6 4 2 0

0 6 12 18 24 30 36 42 (month)

Eve

nt O

ccu

rre

nce

Sym

pto

m R

ate

(%

)

Number of Evaluation Cases

160 150 140 130 120 110 100 90 80 70 60

0 3 6 12 18 24 30 36 42 (month)

Blo

od

Pre

ssu

re

(mm

Hg

)

The Benazepril/Amlodipine

The Benazepril/Hydrochlorothiazide

SBP

DBP Difference in Depressurization between Two Groups

SBP 0.9mmHg P <0.001

DBP 1.1mmHg P <0.001

NICE/BHS criteria

ACEI/ARB or BB CCB/Diuretics

ACEI/ARB + CCB or ACEI/ARB + Diuretics

ACEI/ARB + CCB + thiazide like Diuretics

Add

Low dose spironolactone K < 4.5mmole/L

Further diuretics

Alpha blockers

Beta blockers

Age < 55 years Age ≥ 55 years

Blacks of any age

NICE Clinical guideline

그렇다면 혈관 건강 유지에는

어떤 약물이 효과적일까?

RAS blockade and PWV

Takami T et al. Hypertens Res 2003;26:609-61.4

Effect of combination drug therapy

on Central SBP(J CORE) C

en

tral

systo

lic B

P(m

mH

g)

Matsui Y et al. Hypertension 2009;54:716-723

P = 0.039 (⊿5.2mmHg)

Aldosterone and arterial stiffness

940

960

980

1000

1020

1040

1060

A/R ratio ≥ 20 A/R ratio < 20

hfPWV

(cm/sec) P = 0.010

Park S, Chung N et al. J Hypertens 2007;25(6):1279-1283

Edwards NC et al. J Am Coll Cardiol 2009;54

Should we discard beta

blockers as first line

agents in treatment of

Hypertension Not so

fast!

20

15

10

5

0 0 1 2 3 4 5 6 7 8 9

Years from randomisation

Patients

with

events

(%)

Less tight control

Captopril

Atenolol P=0.28

UKPDS-39 Patients who died of any disease related to diabetes

Mean age: 56, Average BP: 159/94mmHg

Effectiveness of beta

blockers according to age Trial Medication Mean age Initial BP(PP) Result

IPPPSH Oxprenolol vs diuretics 52 173/108(65) Fewer coronary events in

men(non smoker) with

oxyprenolol

MRC mild

hypertension

Propranolol vs diuretics 51 161/98(63) Beta blocker fewer coronary

events but diuretics fewer

stroke

MAPHY Metoprolol vs diuretics 52 167/108(59) Metoprolol superior to

diuretics for coronary events

UKPDS Atenolol vs captopril 56 159/94(65) No significant difference but

trend favoring atenolol for 7

primary endpoints

LIFE Atenolol vs Losartan 67 174/97(77) 25% reduction of stroke with

Losartan

ASCOT BPLA Atenolol ± diureitcs vs

amlodipine ± perindopril

63 164/95(69) 23% reduction of stroke in

amlodipine arm

Effect of beta blockers according to age

Khan N et al. CMAJ 2006;174:1737-1742

Ong WT. BMJ 2007;334:946-949

Effect of baseline HR on the

progression of Hypertension Flemish Study on Environment, Genes and Health Outcomes:

781 women and 675 men followed up for 4.6 years

P=0.037

Zhang H et al. J Hypertens 2006;24:1719-1727

160

150

140

130

120

110

100

90

80

70

60

BP

(mmHg)

and

Heart Rate

In 34 young (28-55yrs) hypertensives, Bisoprolol 5mg was more effective than Amlodipine 5mg, Doxazosin 104mg, Bendrofluazide 2.5mg, Lisinopril 2.5-10mg (double blind, crossover,1 month each)

Deary; Brown et al J. Hypert. 2002

0.4 0.6 0.8 1.0 1.2

Odds Ratio

Controlled

patients* (n = 5253)

Non-controlled

patients (n = 2396)

Hazard Ratio 95% CI

0.4 0.6 0.8 1.0 1.2

Odds Ratio

Fatal/Non-fatal cardiac events ** 0.76

(0.66–0.88) ** 0.73

(0.63–0.85)

Fatal/Non-fatal stroke ** 0.60

(0.48–0.74) ** 0.50

(0.39–0.64)

All-cause death ** 0.79

(0.69–0.91) ** 0.79

(0.69–0.92)

Myocardial infarction 0.83 (0.66–1.03)

0.91 (0.71–1.17)

Heart failure hospitalisations ** 0.62

(0.50–0.77) ** 0.64

(0.52–0.79)

Controlled

patients* (n = 5502)

Non-controlled

patients (n = 2094)

Hazard Ratio 95% CI

Weber MA, et al. Lancet. 2004;363:2049–2051.

*SBP < 140 mmHg at 6 months.

**P < 0.01.

Patients treated with valsartan Patients treated with amlodipine

23

약도 중요하지만 혈압이 얼마나

잘 조절되냐가 가장 중요하다.

70%의 고혈압은 2제 이상을 사용해야 조절이 되면 적절한 조합을 잘 사용하는 것이 중요하다.

ESH/ESC guideline: Diuretics, beta-blockers, CCBs, ACE

inhibitors, and ARBs are all suitable and recommended

either as monotherapy or in some combinations (IA)

대한고혈압학회: Diuretics, beta-blockers, CCBs, ACE

inhibitors, and ARBs

JNC 2013: Diuretics, CCBs, ACE inhibitors, and ARBs

Canadian Hypertension guideline, JSH: Beta blockers not

1st line for patients over the age of 60

NICE: ACEI, ARBs, CCBs

1st line drugs for treatment of Hypertension

Conclusion

한국인에서 혈압조절 및 혈관건강을 호전시키는데 특별히 효과적인 약물이 있는가? 임상연구를 통한 증거는 없지만 이론적으로

calcium channel blocker, 이뇨제, RAS

inhibitor가 효과적일 가능성이 많다

고혈압의 예후와 가장 밀접하게 연관된 것은

목표혈압 이하로 혈압을 조절하는 것이며 그런 측면에서 봤을 때 젊은 고혈압에서는 beta

blocker도 중요한 1차 약제로 생각된다.