2. Global Mortality 2000:
Hypertension is the major risk factor
7.6 million deaths
Developing regions
Developed regions
0
1
2
3
4
5
6
7
8
Attributable mortality in millions (total: 55 861 000)
Adapted from Ezzati et al. Lancet 2002;360:1347-1360.
3. Guidelines: a paradox?
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.“
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.”
European guidelines for the management of arterial hypertension. J Hypertens. 2007, 25:1105–1187
4. Relationship between BP reduction and
cardiovascular outcomes
Relative risk of outcome event
All-cause mortality
Systolic blood pressure difference between randomized groups (mm Hg)
BPLTT Collaboration. Lancet. 2003;362:1527-1535.
5. RAAS inhibitors are the cornerstone
of the antihypertensive treatment
CCB
31%
ACEi plain + comb
RAAS
inhibitors
47%
BB
12%
DIU
10%
ARB plain + comb
MS in prescriptions
Source: IMS. Medical Universe - MAT in prescriptions, 35 countries, 2009
Canada,
Republic,
Kingdom,
United
States,
Austria,
Finland, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands, Poland,
Australia,
Egypt,
Indonesia,
Japan
(includes
hospital
data),
New
Zealand,
Belgium,
Portugal, Slovakia, Spain, Switzerland,
Pakistan,
Philippines,
Saudi
Arabia,
Czech
United
South
6. 2009 Reappraisal of 2007 European Guidelines:
recommended combinations
Diuretics
-blockers
Angiotensin
receptor blockers
Calcium channel
blockers
1-blockers
ACE inhibitors
Preferred combinations
Other possible combinations
J Hypertens. 2007;25:1105–1187.J Hypertens. 2009;27:2121-2158.
7. Reduction in mortality with
amlodipine/perindopril in ASCOT
Cardiovascular mortality
24%, p=0.001
11%, p=0.0247
%
%
10.0
3.5
3.0
atenolol/thiazide
atenolol/thiazide
(No. of events 820)
8.0
(No. of events 342)
2.5
6.0
2.0
4.0
1.5
1.0
amlodipine/perindopril
0.5
0.0
All-cause mortality
(No. of events 263)
0.0
1.0
3.0
2.0
Years
4.0
5.0
2.0
amlodipine/perindopril
(No. of events 738)
0.0
0.0
1.0
2.0
3.0
4.0
5.0
Years
Dahlof B, et al. Lancet. 2005;366:895-906.
8. Components of antihypertensive efficacy…
Prognostic value of blood pressure parameters
… have independent predictive value
3.5
Adjusted 5-year risk of CV death (%)
Nocturnal BP
3.0
24-hour BP
2.5
Daytime BP
2.0
1.5
Conventional
office BP
1.0
N=5292
0.5
90
110
130
150
170
190
210
230
Systolic BP (mm Hg)
Dolan E, et al. Hypertension. 2005;46:156-161.
9. 24 hour antihypertensive efficacy:
trough-to-peak ratio
perindopril
Acertil
Fosinopril
Lisinopril
Ramipril
Benazepril
Enalapril
Telmisartan
Losartan
Valsartan
Olmesartan
Irbesartan
0
10
20
30
40
50
60
70
80
90
100
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.
10. ASCOT: night-time SBP and DBP
Night-time SBP
145
140
135
Night-time DBP
Mean atenolol/thiazide = 125.2 mm Hg
Mean amlodipine/perindopril = 123.0 mm Hg
Mean difference (95% CI) = 2.2 (-3.4, -0.9) mm Hg
P=0.0008
SBP = –2.2 mm Hg
90
85
Mean atenolol/thiazide = 68.6 mm Hg
Mean amlodipine/perindopril = 69.4 mm Hg
Mean difference (95% CI) = 0.8 (0.0-1.6) mm Hg
P=0.0523
DBP = 0.8 mm Hg
80
130
75
125
70
120
65
1
2
3
4
Time (years)
5
1
2
3
4
Time (years)
5
PP = –1.4 mm Hg
amlodipine/perindopril
atenolol/thiazide
Dolan E, et al. J Hypertens 2009.
11. BP variability predicts cardiovascular events
better than does mean brachial systolic BP
Stroke
CHD
By decile of
mean SBP
By decile of
standard
deviation (SD)
in SBP
amlodipine/perindopril
atenolol/thiazide
Rothwell PM, et al. Lancet. 2010;375:895-905.
12. ASCOT: amlodipine/perindopril
lowers BP variability vs atenolol/thiazide
All patients
Mean within-visit CV SBP
4.5
atenolol/bendroflumethiazide
4.3
4.1
3.9
amlodipine/perindopril
3.7
3.5
Follow-up (years)
Baseline 6 W 3 Mths
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
Rothwell PM, et al. Lancet Neurol. 2010;9:469-480.
13. Reduction of central pressure
Brachial systolic
pressure
Central systolic
pressure
mm Hg
mm Hg
0
Athenolol/thiazide
130
5
125
-10
-15
120
-20
115
-25
-30
Amalodipine/perindopril
110
NS
P<0.2
Amlodipine/perindopril
1
Atenolol/thiazide
2
3
4
Time (years)
5
6
Central pressure difference:
- 4.3 mm Hg (P<0.0001)
Williams B, et al. Circulation. 2006;113:1213-1225.
14. 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
15. 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/CDC
Stage 1 H/T--------systolic (140-159 or diastolic(90-99)
Stage 2 H/T--------systolic (>160
or diastolic >100
Recommended----combination of thiazide diuretic and ACEI,ARB or CCB
Goal not achieved---increase the dose and or add drug from different class
16. 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-------------25
Target organ damage/disease
CVD risk
Target
<140 mmHg systolic in age <80
<150 mmHg systolic in age >80
DM
diastolic <85 mmHg
18. New Targets
Treat hypertension >150/90 or higher in
Target---Below this level
age>60 or older
Treat hypertension >140/90 or higher in
CKD or DM regardless of age
age<60 ----30 or patients with
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
