Hypertension:New ConceptNew Targets

2014

Ko Ko

UMMG

Mawlamyaing MMA3.1.14

Global Mortality 2000: Hypertension is the major risk factor

Adapted from Ezzati et al. Lancet 2002;360:1347-1360.

Attributable mortality in millions (total: 55 861 000)

Developing regions

Developed regions

0 87654321

High BP

Tobacco

High cholesterol

Unsafe sex

High BMI

Physical inactivity

Alcohol

Underweight

7.6 million deaths7.6 million deaths

Guidelines: a paradox?

Therapeutic management of hypertension

“Antihypertensive treatment translates into significant reductions of cardiovascular morbidity and mortality while having a less significant effect on all cause mortality.”

Goals of treatment

“The primary goal of treatment of the hypertensive patient is to achieve the maximum reduction in the long-term total risk of cardiovascular morbidity and mortality.“

European guidelines for the management of arterial hypertension. J Hypertens. 2007, 25:1105–1187

Systolic blood pressure difference between randomized groups (mm Hg)

Relationship between BP reduction andcardiovascular outcomes

Rel

ativ

e ri

sk o

f o

utco

me

even

t

BPLTT Collaboration. Lancet. 2003;362:1527-1535.

All-cause mortality

MS in prescriptions

Canada, United States, Austria, Belgium, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands, Poland, Portugal, Slovakia, Spain, Switzerland, United Kingdom, Australia, Egypt, Indonesia, Japan (includes hospital data), New Zealand, Pakistan, Philippines, Saudi Arabia, South Africa, Thailand, Turkey, Argentina, Brazil, Colombia, Mexico, Venezuela.

RAAS inhibitors are the cornerstoneof the antihypertensive treatment

Source: IMS. Medical Universe - MAT in prescriptions, 35 countries, 2009

ACEi plain + comb

CCB31%

DIU10%

BB 12%

ARB plain + comb

RAAS inhibitors

47%

Diuretics

ACE inhibitors

Calcium channel blockers

Angiotensin receptor blockers

-blockers

1-blockers

2009 Reappraisal of 2007 European Guidelines:recommended combinations

J Hypertens. 2007;25:1105–1187.J Hypertens. 2009;27:2121-2158.

Preferred combinations

Other possible combinations

Cardiovascular mortality

amlodipine/perindopril(No. of events 263)

atenolol/thiazide(No. of events 342)

24%, p=0.001

0.0 1.0 2.0 3.0 4.0 5.0Years

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

%

All-cause mortality

0.0 1.0 2.0 3.0 4.0 5.0Years

0.0

2.0

4.0

6.0

8.0

10.0

%

atenolol/thiazide(No. of events 820)

amlodipine/perindopril(No. of events 738)

11%, p=0.0247

Reduction in mortality with amlodipine/perindopril in ASCOT

Dahlof B, et al. Lancet. 2005;366:895-906.

Components of antihypertensive efficacy…… have independent predictive valuePrognostic value of blood pressure parameters

Ad

juste

d 5

-year

risk o

f C

V d

eath

(%

)

Systolic BP (mm Hg)

90 110 130 150 170 190 210 230

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Nocturnal BP

24-hour BP

Daytime BP

Conventional office BP

N=5292

Dolan E, et al. Hypertension. 2005;46:156-161.

0 10 20 30 40 50 60 70 80 90 100

Irbesartan

Olmesartan

Valsartan

Losartan

Telmisartan

Enalapril

Benazepril

Ramipril

Lisinopril

Fosinopril

Acertil

T/P ratio (%)

1. Physicians Desk Reference. NJ: Medical Economics Company; 2008. 2. Diamant H and Vincent HH. Lisinopril versus enalapril: evaluation of trough:peak ratio by ambulatory blood pressure monitoring. J Hum Hypertens. 1999;13:405-412. 3. Martell M, Gill B, Marin R, et al. Trough to peak ratio of once-daily lisinoprol and twice-daily captopril in patients with essential hypertension. J Hum Hypertens. 1998;12:69-72. 4. Hermida RC, Calvo C, Ayala DE, et al. Administration time-dependent effects of valsartan on ambulatory blood pressure in hypertensive subjects. Hypertension. 2000;42:282-290.

24 hour antihypertensive efficacy:trough-to-peak ratio

perindopril

Dolan E, et al. J Hypertens 2009.

ASCOT: night-time SBP and DBP

PP = –1.4 mm Hg

amlodipine/perindopril atenolol/thiazide

Night-time SBP Night-time DBP

145

140

135

130

125

120

1 2 3 4 5

SBP = –2.2 mm Hg

Time (years)

Mean atenolol/thiazide = 125.2 mm HgMean amlodipine/perindopril = 123.0 mm HgMean difference (95% CI) = 2.2 (-3.4, -0.9) mm HgP=0.0008

1 2 3 4 5Time (years)

90

85

80

75

70

65

DBP = 0.8 mm Hg

Mean atenolol/thiazide = 68.6 mm HgMean amlodipine/perindopril = 69.4 mm HgMean difference (95% CI) = 0.8 (0.0-1.6) mm HgP=0.0523

Stroke CHD

BP variability predicts cardiovascular events better than does mean brachial systolic BP

By decile of standard deviation (SD) in SBP

By decile ofmean SBP

amlodipine/perindopril

atenolol/thiazide Rothwell PM, et al. Lancet. 2010;375:895-905.

Rothwell PM, et al. Lancet Neurol. 2010;9:469-480.

ASCOT: amlodipine/perindoprillowers BP variability vs atenolol/thiazide

0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0

Follow-up (years)

4.5

4.3

4.1

3.9

3.7

3.5

All patientsMean within-visit CV SBP

Baseline 6 W3 Mths

amlodipine/perindopril

atenolol/bendroflumethiazide

Reduction of central pressure

Williams B, et al. Circulation. 2006;113:1213-1225.

Amlodipine/perindopril Atenolol/thiazide

Brachial systolicpressure

Central systolicpressure

NSP<0.2

-30

-25

-20

-15

-10

5

0mm Hg

Central pressure difference:- 4.3 mm Hg (P<0.0001)

1 2 3 4 5 6Time (years)

130

125

120

115

110

mm Hg

Amalodipine/perindopril

Athenolol/thiazide

Conclusion • Hypertension is a major risk factor for mortality worldwide

• Reduction in the mortality risk is the ultimate goal of the antihypertensive treatment

• According to our analysis, regimens based on ACE inhibition, in particular with perindopril, significantly improve survival in hypertensive patients

• Benefits of perindopril in monotherapy or in combination with amlodipine or indapamide are strongly supported by evidence from large morbidity-mortality trials (EUROPA, PROGRESS, ADVANCE, HYVET, ASCOT)

• This benefits might not be necessarily shared by other available antihypertensive drugs and their combinations

ASH(American Society of Hypertension) and ISH(International Society of Hypertension Age 80 or more-------- >150/90 CKD and DM----------- <140/90 Age<60-------------------ACEI or ARB(non black) Age >60------------------CCB or Thiazide(non black)

AHA/ACC/CDCStage 1 H/T--------systolic (140-159 or diastolic(90-99)Stage 2 H/T--------systolic (>160 or diastolic >100Recommended----combination of thiazide diuretic and ACEI,ARB or CCBGoal not achieved---increase the dose and or add drug from different class

New European Hypertension Guidelines Released: Goal Is Less Than 140 mm Hg for All(ESH and ESC)

High-normal------systolic (130 to 139 diastolic (85 to 89)Grade 1 H/T--------systolic (140-159 or diastolic(90-99)Grade 2 H/T--------systolic (160-179 or diastolic 100-109)Grade 3 H/T---------systolic (>180 or diastolic >110)

Life style-----salt <5 to 6 gram/day)BMI-------------25Target organ damage/diseaseCVD risk

Target<140 mmHg systolic in age <80<150 mmHg systolic in age >80DM diastolic <85 mmHg

JNC 8

New Targets

Treat hypertension >150/90 or higher in age>60 or older

Target---Below this level

Treat hypertension >140/90 or higher in age<60 ----30 or patients with CKD or DM regardless of age

Initial choice of treatment• For non black including DM-----ACEI/ARB/CCB/Thiazide

diuretic-------first line therapy• For black including DM------------CCB and Thiazide (first

line)• CKD regardless of DM------------ACEI or ARB initial or add

on therapy to improve renal outcome

Date of download: 12/20/2013Copyright © 2012 American Medical Association.

All rights reserved.

From: 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults:  Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)

JAMA. 2013;():. doi:10.1001/jama.2013.284427

Comparison of Current Recommendations With JNC 7 Guidelines

Figure Legend: