1. Blood pressure control in 2017, what do SPRINT and HOPE-3 tell us
林口長庚心臟內科 吳家棟醫師

2. Approximately 20% of the world’s adults are estimated to have hypertension

3. Lewington et al. Lancet 2002;360:1903–13

4. Systolic BP/Diastolic BP (mmHg)
If you don’t control BP
Cardiovascular mortality risk 8
Double Risk
8X risk 6 4
4X risk 2
2X risk
1X risk
115/75
135/85
155/95
175/105
Systolic BP/Diastolic BP (mmHg)
*Individuals aged 40–69 years
Lewington et al. Lancet 2002;360:1903–13

5. If you control BP 7% reduction in risk of IHD mortality
HR for 20mmHg lower usual SBP
Stroke
IHD
Other
0.5
2 mmHg decrease in SBP
7% reduction in risk of IHD mortality
10% reduction in risk of stroke mortality
Lewington et al. Lancet 2002;360:1903–13

6. From database of National Health and Nutrition Examination Survey
The prevalence of resistant hypertension was 8.9% of all US adults with hypertension
From database of National Health and Nutrition Examination Survey
Circulation Apr 3; 125(13): 1594–1596

7. Blood pressure control
???

8. Ideal BP control Where is our target ?
Part I
Ideal BP control Where is our target ?
O vbiagele B, Diener HC, Yusuf S, Martin RH, Cotton D, Vinisko R,
Donnan GA, Bath PM; PRO FESS Investigators. Level of systolic blood
pressure within the normal range and risk of recurrent stroke. JAMA.
2011;306:2137–2144.

9. ???

10. 2013 ESC guideline

11. 2014 JNC 8 guideline BP goal 140/90 mmHg below 60 y/o;
Recommendation 1
In the general population aged ≥60 years, initiate pharmacologic treatment to lower blood pressure (BP) at systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg and treat to a goal SBP <150 mm Hg and goal DBP <90 mm Hg. (Strong Recommendation – Grade A)
Corollary Recommendation
In the general population aged ≥60 years, if pharmacologic treatment for high BP results in lower achieved SBP (eg, <140 mm Hg) and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted. (Expert Opinion – Grade E)
Recommendation 2
In the general population <60 years, initiate pharmacologic treatment to lower BP at DBP ≥90 mm Hg and treat to a goal DBP <90 mm Hg. (For ages years, Strong Recommendation – Grade A; For ages years, Expert Opinion – Grade E)
Recommendation 3
In the general population <60 years, initiate pharmacologic treatment to lower BP at SBP ≥140 mm Hg and treat to a goal SBP <140 mm Hg. (Expert Opinion – Grade E)
Recommendation 4
In the population aged ≥18 years with chronic kidney disease (CKD), initiate pharmacologic treatment to lower BP at SBP ≥140 mm Hg or DBP ≥90 mm Hg and treat to goal SBP <140 mm Hg and goal DBP <90 mm Hg. (Expert Opinion – Grade E)
Recommendation 5
In the population aged ≥18 years with diabetes, initiate pharmacologic treatment to lower BP at SBP ≥140 mm Hg or DBP ≥90 mm Hg and treat to a goal SBP <140 mm Hg and goal DBP <90 mm Hg. (Expert Opinion – Grade E)
Recommendation 6
In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB). (Moderate Recommendation – Grade B)
Recommendation 7
In the general black population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic or CCB. (For general black population: Moderate Recommendation – Grade B; for black patients with diabetes: Weak Recommendation – Grade C)
Recommendation 8
In the population aged ≥18 years with CKD, initial (or add-on) antihypertensive treatment should include an ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status. (Moderate Recommendation – Grade B)
Recommendation 9
The main objective of hypertension treatment is to attain and maintain goal BP. If goal BP is not reached within a month of treatment, increase the dose of the initial drug or add a second drug from one of the classes in recommendation 6 (thiazide-type diuretic, CCB, ACEI, or ARB). The clinician should continue to assess BP and adjust the treatment regimen until goal BP is reached. If goal BP cannot be reached with 2 drugs, add and titrate a third drug from the list provided. Do not use an ACEI and an ARB together in the same patient. If goal BP cannot be reached using only the drugs in recommendation 6 because of a contraindication or the need to use more than 3 drugs to reach goal BP, antihypertensive drugs from other classes can be used. Referral to a hypertension specialist may be indicated for patients in whom goal BP cannot be attained using the above strategy or for the management of complicated patients for whom additional clinical consultation is needed. (Expert Opinion – Grade E)
BP goal 140/90 mmHg below 60 y/o;
150/90 mmHg above 60 y/o.
Grade (A)
140/90 mmHg in CKD patients. Grade (E)
140/90 mmHg in DM patients. Grade (E)
JAMA. 2014;311(5):

12. In 2015,

13. 2015 NEJM SPRINT
9361 patients with >50 y/o and a SBP of mmHg, an increased cardiovascular risk, but without DM
1:1 randomization to target SBP 140 mmHg vs 120mmHg
Primary outcome was CV death, MI or ACS, stroke, or heart failure.
one or more of the following:
clinical or subclinical cardiovascular disease
other than stroke; chronic kidney disease,
excluding polycystic kidney disease, with an estimated
glomerular filtration rate (eGFR) of 20 to
less than 60 ml per minute per 1.73 m2 of bodysurface
area, calculated with the use of the fourvariable
Modification of Diet in Renal Disease
equation; a 10-year risk of cardiovascular disease
of 15% or greater on the basis of the Framingham
risk score; or an age of 75 years or older.
N Engl J Med 2015; 373:

14. SPRINT : Similar study design Same BP Goal Same sphygmomanometer
2010 NEJM ACCORD-BP
4733 patients with DM, SBP of mmHg and > 40y with CVD or > 50y with high risk of CVD
1:1 randomization to target SBP 140 mmHg vs 120mmHg
Primary outcome was CV death, non-fatal MI, or non-fatal stroke.
ACCORD
During management visits , SBP, DBP, and pulse rate
were based on the average of three measurements using an automated device (Omron
907) after 5 minutes rest with the participant seated in a chair
SPRINT
mean of three blood-pressure measurements
at an office visit while the patient was
seated and after 5 minutes of quiet rest; the
measurements were made with the use of an
automated measurement system (Model 907,
Omron Healthcare
N Engl J Med 2010;362:

15. Baseline characteristics
ACCORD vs SPRINT
Baseline characteristics
ACCORD
SPRINT
Diabetes (%)
100 (HbA1c 8.3%)
Age
62.2
67.9
Baseline SBP (mmHg)
139.2
139.7
eGFR (ml/min/1.73m2)
91.6
71.7
Total cholesterol (mg/dL)
192.8
190.1
Previous CVD (%)
33.7
20.1
Current smoking (%)
13.2
12.2
N Engl J Med 2015; 373:
N Engl J Med 2010;362:

16. ACCORD vs SPRINT BP control SPRINT ACCORD ACCORD -14/6 mmHg
SPRINT -13/6 mmHg
ACCORD
ACCORD -14/6 mean number of bloodpressure medications was 3.4 and 2.1
SPRINT -13/6 mean number of bloodpressure medications was 2.8 and 1.8
N Engl J Med 2015; 373:
N Engl J Med 2010;362:

17. ACCORD vs SPRINT Primary outcome ACCORD SPRINT HR 0.88, p=0.20
MI, stroke, CV death
MI/ACS, stroke, HF, CV death
N Engl J Med 2015; 373:
N Engl J Med 2010;362:

18. SPRINT Primary outcome CV death 37 vs 65, HR = 0.57, p = 0.005
Heart failure
62 vs 100, HR = 0.62, p = 0.002
N Engl J Med 2015; 373:

19. ??? ACCORD Primary outcome CV death HR = 1.06, p=0.74 0.52% vs 0.49%
Standard
Intensive
???
SPRINT study (no DM)
0.25% vs 0.43%
CV death
HR = 0.57, p=0.005
N Engl J Med 2010;362:

20. ???

21. According to SPRIND and ACCORD Should we set lower BP goal for patients without DM?
O vbiagele B, Diener HC, Yusuf S, Martin RH, Cotton D, Vinisko R,
Donnan GA, Bath PM; PRO FESS Investigators. Level of systolic blood
pressure within the normal range and risk of recurrent stroke. JAMA.
2011;306:2137–2144.

22. BP control is easier in SPRINT population
ACCORD-BP
Intensive
Standard
ACEI or ARB
90% vs 80% 4+
41% vs 16%
N Engl J Med 2010;362:
SPRINT 4+
24% vs 7%
ACEI or ARB
76% vs 55%
BP control is easier in SPRINT population
N Engl J Med 2015; 373:

23. Same goal, different outcome Why?
1. Difference study population (+/- DM)
2. Different drug, different outcome
Intensive vs. standard group
+21% ACEI/ARB, +11% b-blocker in SPRINT
+10% ACEI/ARB, +18% b-blocker in ACCORD
O vbiagele B, Diener HC, Yusuf S, Martin RH, Cotton D, Vinisko R,
Donnan GA, Bath PM; PRO FESS Investigators. Level of systolic blood
pressure within the normal range and risk of recurrent stroke. JAMA.
2011;306:2137–2144.
More 3rd+ line medication in ACCORD

24. Moving on to 2016,

25. In 2000,
HOPE : ACEI (Ramipril) > placebo on high risk pts
In 2016,
HOPE3 : ARB+HCTZ vs placebo on intermediate risk pts
2016 NEJM HOPE-3
12,705 participants at intermediate risk, who did not have CVD
Candesartan 16 mg + HCTZ 12.5 mg vs placebo First Co-primary outcome: CV death, non-fatal MI, non-fatal stroke
men 55 years of age or older
and women 65 years of age or older who had at
least one of the following cardiovascular risk
factors: elevated waist-to-hip ratio, history of low
concentration of high-density lipoprotein cholesterol,
current or recent tobacco use, dysglycemia,
family history of premature coronary disease, and
mild renal dysfunction
2.7% patients taking OHA,
21.9% patients taking BP lowering medication
N Engl J Med 2016; 375:

26. Systolic BP -6 mmHg MI, stroke, CV death HR = 0.95, p = 0.52
N Engl J Med 2016; 375:

27. Is HOPE-3 a neutral study? Not really !

28. Same drug, similar blood pressure reduction,
HOPE-3 Baseline BP 次族群分析
Same drug, similar blood pressure reduction,
起始血壓較高的患者, 降血壓好處較明顯
N Engl J Med 2016; 375:

29. 血壓是有J curve的 !!! CV event Stroke
Level of systolic blood pressure within the normal range and risk of recurrent stroke. JAMA. 2011;306:2137–2144

30. Cardiovascular mortality increases with follow-up SBP < 120 mmHg in the ONTARGET trial30 3 25
2.5 20 2
Adjusted 4.5-year risk of events, % 15
Hazard ratio, 95 % confidence intervals
1.5 10 1 5
0.5
112
121
126
130
133
136
140
143
149
160
75 % had coronary heart disease at baseline treatment with ACEi and/or ARB.
Sleight et al J. Hypert 2009;27:1360–1369.

31. Cerebral perfusion pressure (CPP)
CPP = MAP – ICP
(50-70 mmHg)
Coronary perfusion pressure (CAPP)
CAPP = DBP – LVEDP
(>50 mmHg)

32. Blood pressure is not the lower the better !!!

33. On the other hand… No pain, no gain…
SPRINT study AE :
Serious AEs:
Hypotension HR 1.67, P=0.001
Syncope HR 1.33, P=0.05
AKI HR 1.66, P<0.001
Net clinical benefit ?
Primary EP : vs 319 (-76)
AKI : vs 117 (+76)

34. SPRINT study : 0% Chinese/Asian

35. b Treat initially to SBP goal of < 140 mm Hg.
If treatment is well tolerated, proceed to < 130 mm Hg.
c Treat to target SBP goal of < 140 mm Hg.
If treatment is well tolerated, proceed < 130 mm Hg.
AramV. Chobanian JAMA. 2017;317(6):

36. 2017 ADA guideline 140/90 mmHg for all DM patients. (A)
Lower target such as 130/80 mmHg may be appropriate for high CV risk individuals, if can be achieved without undue treatment burden (C)

37. 容易控制的血壓嚴格控制
不易控制的血壓降多無益

38. 2015 台灣高血壓治療指引 Goals Systolic Targets
c People with diabetes and hypertension should be treated to a systolic blood
pressure goal of ,140 mmHg. A
c Lower systolic targets, such as ,130 mmHg, may be appropriate for certain individuals
with diabetes, such as younger patients, those with albuminuria, and/or
thosewith hypertension and one ormore additional atherosclerotic cardiovascular
disease risk factors, if they can be achieved without undue treatment burden. C
Diastolic Targets
c Individuals with diabetes should be treated to a diastolic blood pressure goal
of ,90 mmHg. A
c Lower diastolic targets, such as ,80 mmHg, may be appropriate for certain individuals
disease risk factors, if they can be achieved without undue treatment burden. B

39. Ideal BP control How to reach the target ?
Part II
Ideal BP control How to reach the target ?
O vbiagele B, Diener HC, Yusuf S, Martin RH, Cotton D, Vinisko R,
Donnan GA, Bath PM; PRO FESS Investigators. Level of systolic blood
pressure within the normal range and risk of recurrent stroke. JAMA.
2011;306:2137–2144.

40. First line therapy ? Drugs for Hypertension Diuretics β -blocker CCB
1958, first well-tolerable oral agent: Chlorothiazide
Renin inhibitor
Diuretics
Drugs for
Hypertension
Central acting
β -blocker
Vasodilator
CCB
α -blocker
ARB
ACEI
First line therapy ?

41. 2003 JNC 7 guideline
JNC 7. May NIH publication

42. 2002 ALLHAT Chlorthalidone Amlodipine Lisinopril Doxazosin
JAMA. 2002;288(23):

43. Li>Ch (p<0.001), Am=Ch Li=Ch, Am>Ch (p<0.001)
ALLHAT Primary outcome
All-cause Mortality
Li=Ch, Am=Ch
三者差不多
Stroke
Li>Ch (p=0.02), Am=Ch
ACEI比利尿劑差
Combined CV disease
Li>Ch (p<0.001), Am=Ch
ACEI比利尿劑差
Heart Failure
Li=Ch, Am>Ch (p<0.001)
CCB比利尿劑差
Fatal CHD or non-fatal MI
JAMA. 2002;288(23):

44. 為什麼跟我想的不一樣?

45. 用到第二線或第三線藥物的機會 26.7% 25.9% 32.6% Chlothalidone Amlodipine Lisinopril
Mean Systolic BP
Mean Diastolic BP
Participants
were men and women aged 55
years or older who had stage 1 or stage
2 hypertension with at least 1 additional
risk factor for CHD events
JAMA. 2002;288(23):

46. Cardiovascular outcome Amlodipine vs Valsartan
2004 LANCET VALUE
Cardiovascular outcome Amlodipine vs Valsartan
Lancet :

47. Valsartan vs Amlodipine for HTN
Myocardial infarction
Heart failure
V > A p=0.02
V ≤ A p=0.12
Stroke
All cause death
V ≥ A p=0.08
V = A p=0.45
Lancet :

48. Valsartan vs Amlodipine for HTN
Mean systolic BP
Valsartan
Amlodipine
Mean diastolic BP
Valsartan
Amlodipine
Difference
不要小看2 mmHg的差別
Lancet :

49. 降血壓藥物的最重要的好處是來自於降壓本身

50. 2014 JNC 8 guideline
Recommendation 1
In the general population aged ≥60 years, initiate pharmacologic treatment to lower blood pressure (BP) at systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg and treat to a goal SBP <150 mm Hg and goal DBP <90 mm Hg. (Strong Recommendation – Grade A)
Corollary Recommendation
In the general population aged ≥60 years, if pharmacologic treatment for high BP results in lower achieved SBP (eg, <140 mm Hg) and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted. (Expert Opinion – Grade E)
Recommendation 2
In the general population <60 years, initiate pharmacologic treatment to lower BP at DBP ≥90 mm Hg and treat to a goal DBP <90 mm Hg. (For ages years, Strong Recommendation – Grade A; For ages years, Expert Opinion – Grade E)
Recommendation 3
In the general population <60 years, initiate pharmacologic treatment to lower BP at SBP ≥140 mm Hg and treat to a goal SBP <140 mm Hg. (Expert Opinion – Grade E)
Recommendation 4
In the population aged ≥18 years with chronic kidney disease (CKD), initiate pharmacologic treatment to lower BP at SBP ≥140 mm Hg or DBP ≥90 mm Hg and treat to goal SBP <140 mm Hg and goal DBP <90 mm Hg. (Expert Opinion – Grade E)
Recommendation 5
In the population aged ≥18 years with diabetes, initiate pharmacologic treatment to lower BP at SBP ≥140 mm Hg or DBP ≥90 mm Hg and treat to a goal SBP <140 mm Hg and goal DBP <90 mm Hg. (Expert Opinion – Grade E)
Recommendation 6
In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB). (Moderate Recommendation – Grade B)
Recommendation 7
In the general black population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic or CCB. (For general black population: Moderate Recommendation – Grade B; for black patients with diabetes: Weak Recommendation – Grade C)
Recommendation 8
In the population aged ≥18 years with CKD, initial (or add-on) antihypertensive treatment should include an ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status. (Moderate Recommendation – Grade B)
Recommendation 9
The main objective of hypertension treatment is to attain and maintain goal BP. If goal BP is not reached within a month of treatment, increase the dose of the initial drug or add a second drug from one of the classes in recommendation 6 (thiazide-type diuretic, CCB, ACEI, or ARB). The clinician should continue to assess BP and adjust the treatment regimen until goal BP is reached. If goal BP cannot be reached with 2 drugs, add and titrate a third drug from the list provided. Do not use an ACEI and an ARB together in the same patient. If goal BP cannot be reached using only the drugs in recommendation 6 because of a contraindication or the need to use more than 3 drugs to reach goal BP, antihypertensive drugs from other classes can be used. Referral to a hypertension specialist may be indicated for patients in whom goal BP cannot be attained using the above strategy or for the management of complicated patients for whom additional clinical consultation is needed. (Expert Opinion – Grade E)
BP goal 140/90 below 60 y/o and 150/90 above 60 y/o
BP goal 140/90 in DM or CKD patients
ARB = ACEI = CCB = thiazide in non-black patient
ARB or ACEi in CKD patients
Don’t combine ARB and ACEi
JAMA. 2014;311(5):

51. Why not β-blocker at first-line ?

52. 2002 Lancet LIFE study Losartan vs Atenolol for Hypertension + LVH
HR 0.75, p=0.031
55−80 years with hypertension
(either treated or untreated) and signs of LVH on
electrocardiograms
Lancet Mar 23;359(9311):

53. 一樣的降壓效果, 不一樣的患者結果 Total mortality CV mortality Myocardial infarction
Stroke

54. 請問為什麼 ? HR = 1.26 ASCOT- BPLA: Atenolol (+HCTZ) vs. Amlodipine (+ACEI)
Favor atenolol
HR = 1.26
Favor atenolol
Favor other drug
ASCOT- BPLA: Atenolol (+HCTZ) vs. Amlodipine (+ACEI)
INVEST: Atenolol vs. Verapamil
LIFE: Atenolol vs. Losartan
Am J Cardiol 2010;106:1819 –1825

55. Cardiac output = S.V. Heart rate
Pressure = Flow (C.O.) Resistance
Cardiac output
Resistance
β-blocker
α+β blocker
vasodilator

56. 2015 台灣高血壓治療指引

57. 請不要用 β-blocker 作為第一線降壓藥 除非患者有心衰或冠心症

58. Average no. of antihypertensive medications
大多數的患者需要兩種以上的藥物
2 or more drugs required
Average no. of antihypertensive medications
Trial (SBP achieved)
ASCOT-BPLA (136.9 mmHg)
ALLHAT (138 mmHg)
IDNT (138 mmHg)
RENAAL (141 mmHg)
UKPDS (144 mmHg)
ABCD (132 mmHg)
MDRD (132 mmHg)
HOT (138 mmHg)
AASK (128 mmHg)
ACCOMPLISH (132 mmHg)
Initial 2-drug combination therapy
Major clinical trials have demonstrated that patients typically needed treatment with multiple antihypertensive agents to get to, and stay at, blood pressure (BP) goal. The number of antihypertensive agents required for BP control in many patients typically averages 24, with co-morbid conditions (such as kidney disease or diabetes mellitus) imposing greater drug requirement.1,2
For example, in the Hypertension Optimal Treatment (HOT) study, an average of 3.3 drugs were required to attain a diastolic BP goal of <80 mmHg, and in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), most patients were taking at least two antihypertensive agents by the end of the trial.2,3 In the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, patients were receiving initial treatment with single-pill combinations (SPCs) of antihypertensive agents. Excellent BP control rates were obtained with both the SPCs used in the study.4
References
Sica DA. Rationale for fixed-dose combinations in the treatment of hypertension. The cycle repeats. Drugs 2002;62:44362.
Bakris GL, et al. The importance of blood pressure control in the patient with diabetes. Am J Med 2004;116(5A):30S–8S.
Dahlöf B, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005;366:895906.
Jamerson K, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008;359:241728.
MDRD study group, NEJM. 1994;330:877; Kjeldsen et al Hypertension. 1998;31: ; Breener et al NEJM. 2001;345:861-69; Bakris et al. Am J Med. 2004;116(5A):30S–8; Lewis et al, NEJM; 2001;345: ; UKPDS group Lancet, 1998;352: ; AASK research group Arch Intern Med. 2008;168: ; Dahlöf et al. Lancet 2005;366:895–906; van Eijsden et al, Int J Epidemiol. 2011;40: ; ALLHAT research group 2002;288: ; Jamerson et al. N Engl J Med. 2008;359:241728.
Valsartan Family Slide Library Item code: XXXXX.XXX; Release Date: XXXXXXXXXXXXXXXXXX 2013

59. When single drug failed to reach BP target,

60. Recommendations for Combination Therapy
Thiazides
Angiotensin receptor blockers (ARBs)
Calcium channel
blockers (CCBs)
ACE inhibitors
Green continuous
( )
Preferred
Green dashed
( )
Useful
(with some limitations)
Black dashed
( )
Possible but less well-tested
Red continuous
( )
Not recommended
Eur Heart J (2013) doi: /eurheartj/eht151 First published online: June 14, 2013

61. Combination therapy for HTN
A + C
A + D

62. 2008 NEJM ACCOMPLISH Benazepril + hydrochlorothiazide (A+D) versus
beta-blockers, alpha-blockers, clonidine,and spironolactone
11,506 patients with hypertension, high risk for CV events
Initial BP 145/80mmHg
Benazepril + hydrochlorothiazide (A+D) versus
Benazepril + amlodipine (A+C)
N Engl J Med 2008;359:

63. BP control A+D = A+C How about CV outcome ?
N Engl J Med 2008;359:

64. BP control A+D = A+C How about CV outcome ?
The primary end point was the composite of a cardiovascular event and death from cardiovascular causes.
HR 0.8, p<0.001
A+D
A+C
BP control A+D = A+C How about CV outcome ? 勝
N Engl J Med 2008;359:

65. HR 0.52, p<0.001
A+C 優於 A+D
Lancet 2010; 375: 1173–81

66. 2006 NICE/BHS
2011 NICE/BHS
Diuretics are demoted to 3rd-line agents except where there is intolerance to CCBs or when there is a high risk of heart failure.
“A+C” is the only combination recommended .
The “Ds” recommended are either indapamide or chlorthalidone. Thiazides are specifically no longer recommended.

67. Good doctor is not enough, you need co-operative patients
Hospitalization risk decreases at high medication adherence

68. Fixed-dose combination improves adherence
Renin inhibitor
Diuretics
Drugs for
Hypertension
Central acting
β -blocker
Vasodilator
Fixed-dose combination improves adherence
CCB
α -blocker
ARB
ACEi
Melikian C, et al. Clin Ther 2002; 24 (3):

69. At last, cost still matters !!!
Drug
Formulation
Daily cost (NTD)
30-day Cost (NTD)
Amtrel
(Benazepril/Amlodipine)
10/5 mg
12.6
378
Sevikar
(Olmesartan/Amlodipine)
40/5 mg
23.3
699
Exforge
(Valsartan/Amlodipine)
160/5 mg
21.3
639
Twynsta
(Telmisartan/Amlodipine)
80/5 mg
17.4
522
Unisia
(Candesartan/Amlodipine)
8/5 mg
10.8
324
Losartan
Valsartan
Candesartan
Irbesartan
健保用藥品項網路查詢服務 - 中央健康保險局

70. 　　　　《論語·先進》
子貢問：『師與商也孰賢？』
子曰：『師也過，商也不及。』
曰：『然則師愈與？』
子曰：『過猶不及。』
Thank You