PGS TS phamvanbui DIURETICS RAS INHIBITION (1)

LỢI TIỂU và
LỢI TIỂU
KẾT HỢP ARB
trong
BỆNH THẬN MẠN
PGS TS Phạm Văn Bùi
BV Nguyễn Tri Phương
ĐH YK Phạm Ngọc Thạch
GS Thỉnh giảng ĐH Likuk, Belgium


13



Target-organ damage precedes
clinical events
Risk factors: diabetes, obesity, smoking, age

Vasoconstriction
Vascular hypertrophy
Endothelial dysfunction
Atherosclerosis

Apoptosis

Arrhythmia

LVH

Heart failure

Fibrosis

MI

Vascular
disease

Hypertension

Pro-thrombotic
state

Stroke

Death

Cognitive

dysfunction

Decreased GFR
Proteinuria/albuminuria

Renal failure

Glomerulosclerosis
Adapted from: Chung O. & Unger T., Am J Hypertens 1999;12:150S–156S

Risk of CV Mortality Doubles With Each
20/10 mmHg BP Increase
• Meta-analysis of 61 prospective, observational studies/10y

• 1 million adults aged 40–69 y with BP > 115/75 mmHg (w/o previous vascular disease)
• 12.7 million person-years
10

8-fold

Fold increase in
relative CV risk

8
6

4-fold

4
2

2-fold

1-fold

0

115/75

135/85

155/95
SBP/DBP (mmHg)

175/105

Lewington et al. Lancet. 2002;360:1903–1913.


12.000THA/ Veterans Affairs Centers , USA
F-U: 15 năm




Each 10 mmHg Decrease in SBP
Reduces CV Risk by 30-40%
• Meta-analysis of 61 prospective, observational studies10y
• 1 million adults aged 40–69 y with BP > 115/75 mmHg (w/o previous vascular disease)
• 12.7 million person-years

10 mmHg
decrease in
mean SBP

30% reduction in
risk of IHD and other
vascular disease
mortality

40% reduction in risk

of stroke mortality

Lewington et al. Lancet. 2002;360:1903–1913.


Each 2 mmHg Decrease in SBP
Reduces CV Risk by 7–10%
• Meta-analysis of 61 prospective, observational studies10y
• 1 million adults aged 40–69 y with BP > 115/75 mmHg (w/o previous vascular disease)
• 12.7 million person-years

2 mmHg
decrease in
mean SBP

7% reduction in risk
of IHD and other
vascular disease
mortality

10% reduction in risk
of stroke mortality

Lewington et al. Lancet. 2002;360:1903–1913.



(48M-70%))

(68M-31%))

(31M-46%))


The Minority of Patients Achieve
BP Control on Monotherapy
Patients with BP control (%)

40

39

30
20
20
10
0

BP < 140/90 mmHg

Dickerson et al. Lancet. 1999:353:2008–2013.

BP < 135/85 mmHg


Monotherapy for hypertension is not
effective in controlling BP in many patients
80

Cumulative % of patients with BP controlled

(BP <140/90 mm Hg) at five years

66
Percent

60

49

40

26
20

0

1
1

11 or
or 2
2

1 or 2Any
or more

Number of Prescribed Drugs
Cushman et al. J Clin Hypertens. 2002;4:393-404

© Theodore Kurtz, MD

all rights reserved


© Theodore Kurtz, MD
all rights reserved


Hypertension
 Multifactorial disorder
- Many mechanisms involved
- Multiple drugs often required to control BP

 More than just high blood pressure
- Often occurs as part of the metabolic syndrome
- Associated with multiple risk factors for
cardiovascular disease and diabetes
 Current therapies are often inadequate

- Designed to attack only single mechanisms
- Fail to address associated metabolic risk factors
© Theodore Kurtz, MD
all rights reserved


Concept of Metabolic Domino effect
in metabolic syndrome
Lifestyle habit

Postprandial
Hyperglycemia

Hyperlipidemia

Hypertension

Sympathetic nerve system
Renin-angiotensin system

Macro
angiopathy
Diabetes

Micro
angiopathy

Nephropathy Retinopathy

Dialysis

No light
perception

Neurosis

ED

ASO

lower limb
amputation

Cerebrovascular
accident
Apoplexia
Cerebri

Ischemic
cardiac
disease

Dementia

Cardiac
arrest

Hiroshi Ito. Mebio 2005; 22: 125-8







Combination therapy means more consistent
effect, regardless of underlying causes of
hypertension (ISN Canada, 2011)

RAS

Na+

+
Na

RAS
ACEI/ARB
CCB
DIURETIC

RAS

+++
++
+

ACEI/ARB + CCB ++++
ACEI/ARB + Diuretic ++++

ACEI/ARB
CCB
DIURETIC

+
Na
++
++
++

ACEI/ARB + CCB ++++
ACEI/ARB + Diuretic ++++

ACEI/ARB
CCB
DIURETIC

+
+++
+++

ACEI/ARB + CCB ++++
ACEI/ARB + Diuretic ++++


Khuyến cáo 2007 ESH/ESC
Kết hợp ngay hai loại thuốc hạ áp nếu:
• HA cao lúc bắt đầu điều trị
• Có nguy cơ tim mạch cao/rất cao, biểu hiện:
• Tổn thương cơ quan đích
• Bệnh thận
• Tiền sử bệnh tim mạch

Stefano Taddei et al. Am J Cardiovasc Drugs. 2011;11(1):13-20


• Hypertension is a complex disorder
→ a combination of pills if they are going
to reach target
• JNC 7 guidelines in the US recommend:
consideration of initial combination
treatment in patients > 20/10 mm Hg

above target BP
• ESH :
initial combination therapy advised for
"high-risk" patients
Lisa Nainggolan. Heartwire © 2011 Medscape