110/04/15-從基層新代科觀點看血壓

1. 從基層新陳科觀點看血壓
曾競鋒
2021-4-15

2. 基層/新陳代謝科
• 基層的高血壓治療：
• 藥品：與醫學中心沒有差別
• 相關檢查/檢驗：略有差別
• 新陳代謝科：
• 糖尿病
• 糖尿病的併發症
• 慢性腎臟病

3. Clinical
Evidence
Treatment
Guidelines
Clinical
Practice
Real world
Data

4. 目前最重要的腦心腎守護血壓藥
•ACEI: HOPE 集大成
•ARB: ON TARGET 集大成

7. • 血壓控制與併發症
• LIFE, SCOPE
• 糖尿病小血管併發症的預防
• RENAAL, PRIME (IRMA II, IDNT), ROADMAP (腎病變)
• DIRECT (眼病變)
• 心臟衰竭
• CHARM, Val-Heft, ELITE I, II …
• ON Target (集大成)
ARB 的重要歷史事件

15. 2000 (HOPE) 2008 (ON TARGET)
•2020 ISH Hypertension guidelines
•2021 ADA DM with hypertension treatment
•2020 KDIGO

23. Essential test
Laboratory Investigations and ECG
• Blood tests: Sodium, potassium, serum creatinine and estimated
glomerular filtration rate (eGFR). If available, lipid profile and fasting glucose.
• Urine test: Dipstick urine test.
• 12-lead ECG: Detection of atrial fibrillation, left ventricular hypertrophy
(LVH), ischemic heart disease.
Optinal Investigations
• Ankle-brachial index: Peripheral (lower extremity) artery disease.
• Further testing for secondary hypertension if suspected: Aldosterone-renin ratio,
plasma free metanephrines, late-night salivary cortisol or other screening tests for
cortisol excess.
• Urinary albumin/creatinine ratio
• Serum uric acid (s-UA) levels
• Liver function tests

28. 鹽、飲食、飲料、
酒、體重、戒煙、
運動、壓力、替代
療法、空污、冷

33. a) Consider monotherapy in low risk grade 1 hypertension or in very
old (≥ 80 yrs) o r frailer patients.
b) Consider A + D in post-stroke, very elderly, incipient heart failure
or CCB intolerance.
c) Consider A + C or C + D in black patients.
d) Caution with spironolactone or other potassium sparing diuretics
when estimated GFR <45 ml/min/1.73m2 or K+ >4.5 mmol/L.
A = ACE-Inhibitor or ARB (Angiotensin Receptor Blocker)
C = DHP-CCB (Dihydropyridine -Calcium Channel Blocker)
D = Thiazide-like diuretic

34. SPC
Once daily
Daily habits
HBPM
Package
Electronic aid
Team approach

35. Lifestyle
LDL-C
Sugar (A1C)
S-UA
Antiplatelet (2nd)

38. • A strong epidemiological interaction exists between CAD and hypertension
that accounts for 25%–30% of acute myocardial infarctions.88
• Lifestyle changes are recommended (smoking cessation, diet and exercise).
• BP should be lowered if ≥140/90 mmHg and treated to a target <130/80
mmHg (<140/80 in elderly patients).
• RAS blockers, beta-blockers irrespective of BP levels with or without
calcium channel blockers (CCBs) are first-line drugs in hypertensive
patients.1
• Lipid-lowering treatment with an LDL-C target <55 mg/dL (1.4 mmol/L).89
• Antiplatelet treatment with acetyl salicylic acid is routinely recommended.
Hypertension and Coronary Artery Disease (CAD)

39. Hypertension and Previous Stroke
• Hypertension is the most important risk factor for ischemic or hemorrhagic
stroke.90
• Stroke can be largely prevented by BP control.
• BP should be lowered if ≥140/90 mmHg and treated to a target <130/80
mmHg (<140/80 in elderly patients).1
• RAS blockers, CCBs, and diuretics are first-line drugs.1
• Lipid-lowering treatment is mandatory with a LDL-C target <70 mg/dL (1.8
mmol/L) in ischemic stroke.1
• Antiplatelet treatment is routinely recommended for ischemic stroke, but
not hemorrhagic stroke, and should be carefully considered in patients with
hemorrhagic stroke only in the presence of a strong indication.1

40. Hypertension and Heart Failure (HF)
• Hypertension is a risk factor for the development of HF with reduced ejection
fraction (HFrEF), and with preserved ejection fraction (HFpEF). Clinical outcome is
worse and mortality is increased in hypertensive patients with HF.2
• Lifestyle changes are recommended (diet and exercise).
• Treating hypertension has a major impact on reducing the risk of incident HF and
HF hospitalization. BP should be lowered if ≥140/90 mmHg and treated to a target
<130/80 mmHg but >120/70 mmHg.
• RAS blockers, beta-blockers, and mineralocorticoid receptor antagonists are all
effective in improving clinical outcome in patients with established HFrEF, whereas
for diuretics, evidence is limited to symptomatic improvement.1 CCBs are indicated
on in case of poor BP control.
• Angiotensin receptor-neprilysin inhibitor (ARNI; sacubitril-valsartan) is indicated
for the treatment of HFrEF as an alternative to ACE inhibitors or ARBs also in
hypertensive populations. The same treatment strategy can be applied to patients
with HFpEF even if the optimal treatment strategy is not known.91

41. Hypertension and Chronic Kidney Disease (CKD)
• Hypertension is a major risk factor for the development and progression of
albuminuria and any form of CKD.92
• A lower eGFR is associated with resistant hypertension, masked hypertension, and
elevated nighttime BP values.92
• The effects of BP lowering on renal function (and albuminuria) are dissociated
from cardiovascular benefit.1
• BP should be lowered if ≥140/90 mmHg and treated to a target <130/80 mmHg
(<140/80 in elderly patients).1
• RAS-inhibitors are first-line drugs because they reduce albuminuria in addition to
BP control. CCBs and diuretics (loop-diuretics if eGFR <30 ml/min/1.73m2 ) can be
added.1
• eGFR, microalbuminuria and blood electrolytes should be monitored.1

42. Hypertension and Chronic Obstructive
Pulmonary Disease (COPD)
• Hypertension is the most frequent comorbidity in patients with COPD. BP should be
lowered if ≥140/90 mm Hg and treated to a target <130/80 mm Hg (<140/80 in
elderly patients).
• Lifestyle changes (smoking cessation) are mandatory.93
• Environmental (air) pollution should be considered and avoided if possible.93
• The treatment strategy should include an angiotensin AT1 -receptor blocker (ARB)
and CCB and/or diuretic, while beta blockers (ß1 -receptor selective) may be used in
selected patients (eg, CAD, HF).
• Additional cardiovascular risk factors should be managed according to
cardiovascular risk profile.

43. Diabetes
• BP should be lowered if ≥140/90 mmHg and treated to a target
<130/80 mm Hg (<140/80 in elderly patients).96
• The treatment strategy should include an RAS inhibitor (and a
CCB and/or thiazide-like diuretic).
• The treatment should include a statin in primary prevention if
LDL-C >70 mg/dL (1.8 mmol/L) (diabetes with target organ
damage) or >100 mg/dL (2.6 mmol/L) (uncomplicated diabetes).
• The treatment should include glucose and lipid lowering as per
current guidelines (see Section 11: Resources).

44. Lipid Disorders
• BP should be lowered as done in the general population, preferentially
with RAS-inhibitors (ARB, ACE-I) and CCBs.97
• Statins are the lipid-lowering treatment of choice with or without
ezetimibe and/or PCSK9 inhibitor (in the optimal setting).98
• Serum triglyceride lowering should be considered if >200 mg/dL (2.3
mmol/L) particularly in patients with hypertension and DM. Possible
additional benefits using fenofibrate in low HDL/high triglyceride
subgroup.

45. 共病的高血壓治療
•共同的血壓目標
•< 130/80 mmHg
•<140/80 mmHg elderly
•共同的第一線用藥
•RAS blockade

47. 每一次回診，
反覆確認
每個糖友都要
做HBPM

48. 大多數 <130/80 mmHg
低風險 < 140/90 mmHg
孕婦 110-135/85 mmHg

49. >120/80 mmHg, DASH and lifestyle
>140/90 mmHg 立即治療並調整用藥

50. >=160/100 mmHg, SPC
First line: ACEI or ARB (不可併用)
MAU or above, high dose, F/U K, eGFR
A+C+D+MCRA

55. CKD is defined as abnormalities of kidney structure or function, present for >3 months, with implications for health. CKD is classified
based on Cause, GFR category (G1–G5), and Albuminuria category (A1–A3), abbreviated as CGA.

56. Figure 2 | Kidney–heart risk factor management.
 SGLT2i and RAS blockade are recommended for most patients

57. Figure 4 | Monitoring of serum creatinine and potassium during ACEi or ARB treatment—dose adjustment and monitoring of side effects.
ACEI/ARB

58. ISH, ADA, KDIGO 小結論 (1)
• 不可忘記非藥物治療
• ISH:
• General: A+C low dose  full dose  A+C+D  A+C+D+spironolactone
• BB: only indicated
• ADA:
• If CKD or CAD: A  A+(C or D)  A+C+D
• If no  A or C or D  A+C, A+D, C+D  A+C+D
• KDIGO (CKD): A
• If eGFR, K problem, correction, if possible, keep A
• If no problem, high dose A

59. • SPC
• Once daily
• Daily habits
• HBPM
• Package
• Electronic aid
• Team approach
ISH, ADA, KDIGO 小結論 (2)

60. 重要訊息
•ACEI, ARB
•If MAU or above or CKD, high dose
•SPC
•Well tolerated (ARB > ACEI)

61. • Double chain domain
獨具化學結構

62. Neutral antagonists
agonists
Inverse agonists
(Olmesartan)
Ligand (Log A)
[RWT]
[R*WT]
[R’WT]
Spontaneous
and
Consititutive
Activity
Inactive state
Partial active state
Full active state
(Miura S, et al. Curr Hypertens Rev. 2005)
What is an Inverse Agonist?

63. Lack of Hydroxyl Group
decreases Inverse Agonist effect
（Marker of Endogenous Activation）
Double-Chain Domain is important for inverse agonism
IP Production of AT1-F11A/N111G Mutant Receptor
Miura S et al.:JBC 281(28):19228 -19295,2006
0
20
40
60
80
100
120
(%)
*
None Olmesartan
Inositol
phosphate
production
N
N
COOH
N
H
N
N
N
OH
Me
CH 3 CH 3
N
N
COOH
N
H
N
N
N
H
Me
CH 3 CH 3
-OH
*: P<0.05 vs Olmesartan w/o OH
Olmesartan
w/o OH

64. • 4 binding sites
更強的結合
AT
AT1
1 Receptor
Receptor
Binding
Binding site
site of
of Ang
Ang II
II
Double Chain Domain
Double Chain Domain
Gln
Gln257
257
His
His256
256
Lys
Lys199
199
Tyr
Tyr113
113
COOH
COOH
OH
OH
Tyr
Tyr113
113
Lys
Lys199
199
Gln
Gln257
257
His
His256
256
V
VI
VII
II III
IV
I Top view
Side view
Molecular modeling of interaction
between AT1 Receptor and olmesatan
Olmesartan
Olmesartan
（
（Hanzawa
Hanzawa H &
H &
Miura S. 2005
Miura S. 2005）
）

65. ARB中
降壓效果最快
2週達最大降壓效果
仿單記載確證: 相較於其他ARB需4-6週
0
week
2
week
4
week
6
week
OLM
20-40 mg
LOS
50-100 mg
IRB
150-300 mg
VAL
80-160 mg
Olsaa® 仿單，Telmisartan、Valsartan、Losartan、Irbesartan 仿單
TEL
40-80 mg

66. • Systematic review of the antihypertensive activity
of ARBs: BP reduction over 24 hours

67. Olmesartan is suggested to be more
effective than Telmisartan for BP control
Drug Design, Development and Therapy 2014:8

68. Olmesartan 24Hr血壓控制效果優於Telmisartan
Comparison of reduction in diastolic and systolic blood pressure in treatment groups after 12 weeks. #P < 0.0001 when compared with losartan
group; $P < 0.0001 when compared with telmisartan group; ΦP < 0.001 when compared with losartan group; ΨP < 0.01 when compared with
losartan group

69. CHAOS study
Olmesartan is a better choice than azilsartan! (Edarbi® )
More over, left ventricular
mass index is significantly
smaller in olmesartan group
than azilsartan group after 1
year treatment.
Sezai A, et al.
Inhibitory effect on cardiac hypertrophy
Ann Thorac Cardiovasc Surg Advance Published Date: April 18, 2016

70. 有效改善糖尿病腎病變
86
CKD
stage Ⅰ Ⅱ Ⅲ Ⅳ Ⅴ Dialysis
Olmesartan
86

71. N Engl J Med. 2011 Mar 10;364(10):907-17.
Occurrence of Microalbuminuria during the 48-Month Follow-up Period in the Two Study Groups.
23% Microalbuminuria
ROADMAP Trial
CKD Stage 2
可有效降低糖尿病病人發生微蛋白尿的風險
40mg/QD
(微蛋白尿)

72. Diabetologia (2011) 54:2978–2986
Olmesartan
Placebo
0.64 (0.43, 0.98; p=0.039) p=0.005
ORIENT Trial
降低糖尿病腎病變病患蛋白尿
及心血管疾病發生率
CKD Stage 3~5
糖尿病人的
心血管疾病發生率降低36%
糖尿病人的
蛋白尿降低40%
10-40mg/QD

73. Olmesartan 顯著抗發炎作用
EUTOPIA study

74. Olmesartan 顯著降低血管的肥厚現象
VIOS study

75. Olmesartan 可抗動脈粥狀硬化
MORE & OLIVUS study

76. 不只降壓效果!
Olmesartan更帶來完整的心血管保護
Olmesartan and vascular protection: Summary ofevidences

77. ARB 比較表
學名/劑量
Olmesartan
40mg
Telmisartan
80mg
Valsartan
160mg
Irbesartan
300mg
Losartan
100mg
與AT1 Receptor
作用方式 4結合點 3結合點 2結合點 2結合點 2結合點
經由Cytochrome
P450代謝
No No No Yes Yes
T 1/2(Hrs) 13 24 5-9 11-15 6-9
Food effect No No No No No
Time to BP
effect (weeks)
2 4 4 4-6 4-6
AT(1) receptor
selectivity
A C C B C
代謝途徑
腎: 50%
肝臟:50%
腎: <1%
肝臟:>97%
腎: 13%
肝臟:83%
腎: 20%
肝臟:80%
腎: 35%
肝臟:60%
109.10.01年健保價 14.5 13.1 8.2 10.3 6.6
A, highest level of affinity; B, second in line after A; C, third in line after A and B
Vascular Health and Risk Management 2011:7

78. 原廠認證品質

79. ESTENGY®
SPC

81. J Clin Hypertens. 2008 Mar;10(3):185-94.
Stage I~II HTN
服用單錠複方八週後，可多有效
降低坐姿收縮壓達17.4~18.4 mmHg
單方複方
Estengy®
(A+C)
Val 160 mg
Amlo 10 mg

84. 結論
• HOPE (2000),
• OnTARGET (2008)
• ISH 2020
• ADA 2021
• KDIGO
• HBPM
• Lifestyle
• ACEI/ARB
• SPC
• high dose ACEI/ARB
• Olsaa® 20, 40 mg, estengy® (5/80, 5/160 mg)
預防勝於治療
謝謝大家