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: