TERAPIA DELL’IPERTENSIONE
ARTERIOSA e CONTINUUM
CARDIOVASCOLARE
ETTORE MALACCO
Ospedale L. Sacco - Polo Universitario - Milano
Dalle linee guida………….
2003 European Society of Hypertension - European Society of
Cardiology guidelines for the management of arterial hypertension
Definitions and classification of blood pressure levels (mmHg)
Category
Systolic
Diastolic
Optimal
Normal
High
-normal
High-normal
Grade 1 hypertension (mild)
Subgroup: borderline
Grade 2 hypertension (moderate)
Grade 3 hypertension (severe)
< 120
< 130
130 - 139
140 - 159
140 - 149
160 - 179
> 180
< 80
< 85
85 - 89
90 - 99
90 - 94
100 - 109
> 110
Isolated systolic hypertension
Subgroup: borderline
> 140
140 - 149
< 90
< 90
Isolated systolic hypertension can also be graded according to systolic
blood pressure values (grades 1, 2, 3).
Stratification of Risk to Quantify Prognosis
Blood Pressure (mmHg)
Other Risk Factors
& Disease History
Grade 1
Grade 2
Grade 3
(mild hypertension)
(moderate hypertension)
(severe hypertension)
SBP 160-179
or DBP 100-109
SBP > 180
or DBP > 110
SBP 140-159
or DBP 90-99
I no other
risk factors
LOW RISK
MED RISK
HIGH RISK
II 1-2 risk factors
MED RISK
MED RISK
V HIGH RISK
HIGH RISK
HIGH RISK
V HIGH RISK
V HIGH RISK
V HIGH RISK
V HIGH RISK
III 3 or more risk
factors or TOD or
diabetes
IV ACC
TOD - TargetTarget-organ damage
ACC - Associated clinical conditions
Stratification of Risk to Quantify Prognosis
Blood Pressure (mmHg)
Other Risk Factors
& Disease History
I no other
risk factors
Normal
SBP 120-129
or DBP 80-84
AVERAGE RISK
High normal
SBP 130-139
or DBP 85-89
AVERAGE RISK
II 1-2 risk factors
LOW ADDED
RISK
LOW ADDED
RISK
III 3 or more risk
factors or TOD or
diabetes
MODERATE
ADDED RISK
HIGH
ADDED RISK
VERY HIGH
HIGH
ADDED RISK
ADDED RISK
TOD - Target-organ damage ACC - Associated clinical conditions
IV ACC
In persons older than 50 years, systolic blood
pressure greater than 140 mmHg is a much important
cardiovascular disease (CVD) risk factor than
diastolic blood pressure.
The risk of CVD beginning at 115/75 mmHg doubles
with each increment of 20/10 mmHg; individuals who
are normotensive at age 55 have a 90 percent lifetime
risk for developing hypertension.
Individuals with a systolic blood pressure of 120-139
mmHg or a diastolic blood pressure of 80-89 mmHg
should be considered as prehypertensive and require
health-promoting lifestyle modifications to prevent
CVD.
……………………….
Effects of different blood-pressure-lowering regimens on major
cardiovascular events:
results of prospectively-designed overviews of randomised trials
Blood Pressure Lowering Treatment Trialists’ Collaboration
World Health Organization-International Society of hypertension
(WHO-ISH) Blood Pressure Lowering Treatment Trialists’ Collaboration
L. Agodoa, C. Baigent, H. Black, J.P. Boissel, B. Brenner, M. Brown, C. Bulpit, R. Byington,
J. Chalmers, R. Collins, J. Cutler, B. Dahlof, B. Davis, R. Estacio, R. Fagard, K. Fox, C. Furberg,
L. Hansson, R. Holman, L. Hunsicker, J. Kostis, K. Kuramoto, J. Kusek, R. Lees, E. Lewis,
L. Lindholm, L. Liu, J. Lubsen, S. MacMahon, E. Malacco, G. Mancia, I. Martin, S. Mendis,
B. Neal, C. Pepine, M. Pfeffer, B. Pitt, P. Poole-Wilson, G. Remuzzi, A. Rodgers, R. Schrier,
P. Sever, P. Sleight, J. Staessen, K. Teo, R. Turner, P. Whelton, L. Wing, S. Yusuf, A.Zanchetti
Lancet 2003; 362: 1527-35
Effects of blood pressure lowering regimens based on different
drug classes on the risks of major vascular outcomes and death
Mean
Mean blood
blood pressure
pressure
difference
difference (mmHg)
(mmHg)
Favours
Favours
first
first listed
listed
Favours
Favours Relative
Relative risk
risk
second
second listed
listed (95%CI)
(95%CI)
Stroke
Stroke
Coronary
Coronary heart
heart disease
disease
Heart
Heart failure
failure
0.5
1.0
Relative risk
2.0
Mean
Mean blood
blood pressure
pressure
difference
difference (mmHg)
(mmHg)
Major
Major cardiovascular
cardiovascular events
events
Cardiovascular
Cardiovascular death
death
Total
Total mortality
mortality
Favours
Favours
first
first listed
listed
Favours
Favours
second
second listed
listed
Relative
Relative risk
risk
(95%CI)
(95%CI)
INTERPRETATION
These overwies confirm and extend the evidence of
beneficial effects of blood-pressure
lowering regimens.
Aside from lesser effects of calcium antagonists on the risk
of heart failure, there was no clear evidence that
particular drug classes conferred greater or lesser
benefits for any outcome. The intensity of blood
pressure reduction appears to be a more important
determiant of outcome than the drug class selected.
ANTIHYPERTENSIVE DRUGS
Diuretics
Guanethidine
1960
Reserpine
Methyldopa
Clonidine
Ca++-antagonists
Prazosin
ACE inhibitors
Angiotensin II
receptors antagonist
β-blockers
1970
1980
1990
Sistema RAA e
Continuum cardiovascolare
ARBs
Sistema RAA
Disfunzione
Disfunzione
endoteliale
endoteliale
ATS
ATS coronarica
coronarica
Ipertensione,
Ipertensione,
Fumo,
Fumo,
Dislipidemia,
Dislipidemia,
Diabete,
Diabete, Obesità
Obesità
VS
VS normale
normale
Anni
Anni
IMA
scompenso
scompenso acuto
acuto
oo disfunzione
disfunzione
sistolica
sistolica
Scompenso
Scompenso
cronico
cronico
Rimodellamento
Rimodellamento
Anni
Anni oo mesi
mesi
Dilatazione
Dilatazione
Morte
Morte
THE EFFICACY AND TOLERABILITY OF VALSARTAN VERSUS
LISINOPRIL
-BASED TREATMENT
LISINOPRIL-BASED
IN PATIENTS WITH MILD TO MODERATE HYPERTENSION
THE PREVAIL STUDY
E. Malacco et al., Clinical Therapeutics: Vol 26, No. 6, 2004
OBJECTIVE
To compare the efficacy and tolerability of valsartan given
160 mg o.d. with that of lisinopril given 20 mg o.d., either
alone or combined with hydrochlorothiazide 12.5 mg, in
patients with mild to moderate hypertension.
The primary endpoint was to show that equipotency in
blood pressure reduction is accompanied by superiority
in tolerability profile of valsartan-based treatment.
0
-5
-10
-15
-20
-25
-30
-35
-15,4 -15,5
-30,2 -30,5
PAS
valsartan (n=594)
Incidenza di effetti collaterali
farmaco correlati (%)
PAD
lisinopril (n=591)
12
9
% pazienti
pazienti
%
Riduzione pressoria
(mm Hg)
Riduzione dei valori pressori sistolici e diastolici
al termine del trattamento rispetto al basale
P = 0.001
10,7
6
3
5,1
0 valsartan (n=604)
lisinopril (n=609)
CONCLUSION
Valsartan 160 mg o.d. and lisinopril 20 mg o.d. either alone
or combined with hydrochlorothiazide 12.5 mg are both
highly effective in controlling BP in patients with mild to
moderate hypertension.
However, valsartan offers a significant tolerability
advantage as it shows a reduced risk of developing
adverse events.
New Issues of the Treatment of
Isolated Systolic Hypertension
The newest hot issue in the field of hypertension
relates to the oldest isolated systolic hypertension
(ISH) in the elderly……
N.M. Kaplan, MD
Circulation 5 September 2000; 102 :1079-1081
A Randomized, Double-Blind, Active-Controlled,
Parallel-Group Comparison of Valsartan and Amlodipine
in the Treatment of Isolated Systolic Hypertension
in Elderly Patients
The Val-Syst Study
E. Malacco et al, Clinical Therapeutics - Vol. 25, No. 11, 2003
Primary objectives
To compare the antihypertensive effect on systolic
blood pressure (SBP) of a valsartan-based treatment
with that of an amlodipine-based treatment, both
administered for 24 weeks and tailored to get a sitting
SBP < 140 mmHg, in patients aged 60 to 80 years
with isolated systolic hypertension.
To compare the tolerability of the two treatments.
Flow Chart
V 160 +
HCTZ 12.5**
V 160**
V 80
Placebo
Wash-out
A5
week
visit
-2
1
0
2
4
3
A 10**
8
4
12
5
A 10 +
HCTZ 12.5**
16
6
20
7
24
8
** when
when SBP
SBP ≥ 140
140 mmHg
mmHg
Blood Pressure Reduction after 24 weeks
0
SBP
-5
-6,0
-10
mmHg
DBP
-6,5
-15
-20
-25
valsartan
amlodipine
-30
-35
-33,4 -33,5
Tolerability
valsartan
amlodipine
208
42 (20.2)
10 (4.8)
213
68 (31.9)
57 (26.8)
12 (5.8)
8 (3.8)
6 (2.9)
5 (2.4)
5 (2.4)
3 (1.4)
1 (0.5)
3 (1.4)
3 (1.4)
2 (1.0)
2 (1.0)
1 (0.5)
7 (3.3)
11 (5.2)
2 (0.9)
4 (1.9)
0 (0.0)
5 (2.3)
5 (2.3)
3 (1.4)
2 (0.9)
2 (0.9)
0 (0.0)
0 (0.0)
n (%)
Randomised
Patients with AE
• edema
• headache
• viral infection
• diarrhoea
• dizziness
• nausea
• upper resp. tract infection
• flushing
• cough
• somnolence
• abdominal pain
• palpitations
• fatigue
n (%)
Sistema RAA e
Continuum cardiovascolare
ARBs
ARBs
Sistema RAA
Disfunzione
Disfunzione
endoteliale
endoteliale
ATS
ATS coronarica
coronarica
Ipertensione,
Ipertensione,
Fumo,
Fumo,
Dislipidemia,
Dislipidemia,
Diabete,
Diabete, Obesità
Obesità
VS
VS normale
normale
Anni
Anni
IMA
scompenso
scompenso acuto
acuto
oo disfunzione
disfunzione
sistolica
sistolica
Scompenso
Scompenso
cronico
cronico
Rimodellamento
Rimodellamento
Anni
Anni oo mesi
mesi
Dilatazione
Dilatazione
Morte
Morte
HF HOSPITALIZATION
Event-Free Probability
1.0
27.5% Risk Reduction
P = 0.00001
0.9
Valsartan
0.8
Placebo
0
3
6
9
12 15 18 21 24
Time Since Randomization (Months)
27
Sistema RAA e
Continuum cardiovascolare
ARBs
ARBs
ARBs
Sistema RAA
Disfunzione
Disfunzione endoteliale
endoteliale
ATS
coronarica
ATS coronarica
Ipertensione, Fumo,
Dislipidemia,
Diabete, Obesit ˆ
VS normale
Anni
IMA
IMA
scompenso
scompenso acuto
acuto oo
disfunzione
sistolica
disfunzione sistolica
Scompenso
cronico
Optimaal
CHARM
Rimodellamento
Anni o mesi
Dilatazione
Morte
00
25
25
Losartan
20
20
Captopril
NS
NS
CV
CV
Mortality
Mortality
NS
NS
Admission
Admission
for HF
HF
for
30
30
Death and
and MI
MI
Death
15
15
Reinfarction
Reinfarction
All-cause
All-cause
mortality
mortality
OPTIMAAL Trial
NS
NS
P
P == 0.03
0.03
NS
NS
10
10
55
Sistema RAA e
Continuum cardiovascolare
ARBs
ARBs
ARBs
Sistema RAA
Disfunzione
Disfunzione endoteliale
endoteliale
ATS
ATS coronarica
coronarica
Ipertensione, Fumo,
Dislipidemia,
Diabete, Obesit ˆ
VS normale
Anni
IMA
IMA
scompenso
scompenso acuto
acuto oo
disfunzione
disfunzione sistolica
sistolica
Scompenso
cronico
Optimaal
CHARM
Rimodellamento
Anni o mesi
Dilatazione
Morte
Valiant - Conclusion
In patients with MI complicated by heart failure, left ventricular
dysfunction or both:
Valsartan is as effective as a proven dose of captopril in reducing
the risk of:
Death
CV death or non-fatal MI or heart failure admission
Sistema RAA e
Continuum cardiovascolare
ARBs
ARBs
ARBs
Sistema RAA
Disfunzione
Disfunzione endoteliale
endoteliale
ATS
ATS coronarica
coronarica
Ipertensione, Fumo,
Dislipidemia,
Diabete, Obesit ˆ
VS normale
Anni
IMA
scompenso
scompenso acuto
acuto oo
disfunzione
disfunzione sistolica
sistolica
Scompenso
cronico
Optimaal
CHARM
Rimodellamento
Anni o mesi
Dilatazione
Morte
VALUE
Valsartan Antihypertensive
Long-Term Use Evaluation
Primary Hypothesis
In hypertensive patients at high cardiovascular
risk, for the same level of blood pressure control,
valsartan will be more effective than amlodipine in
reducing cardiac morbidity and mortality
Julius
Julius S
S et
et al.
al. Lancet.
Lancet. June
June 2004;
2004; 363.
363.
Primary Endpoint
Composite cardiac morbidity and mortality
sudden cardiac death
fatal/nonfatal MI
evidence of recent MI on autopsy
emergency thrombolytic
/fibrinolytic treatment and/or emergency
thrombolytic/fibrinolytic
PTCA/CABG to avoid MI
death during/after PTCA/CABG
new or chronic CHF requiring hospital management
hheart
eart failure death
Mann
Mann J,
J, Julius
Julius S.
S. Blood
Blood Press.
Press. 1998;7:176–183.
1998;7:176–183.
Secondary Endpoints and
Pre-specified Analyses
Secondary Endpoints:
fatal/non-fatal myocardial infarction
fatal/non-fatal stroke
fatal/non-fatal heart failure
Pre-specified Analyses:
all-cause mortality
new-onset diabetes
Julius
Julius S
S et
et al.
al. Lancet.
Lancet. June
June 2004;
2004; 363.
363.
Design
Elective titration to target BP (<140/90 mmHg)
ValsartanValsartanbased
based regimen
regimen
V
V 160
160 mg
mg ++
HCTZ
HCTZ 12.5
12.5 mg
mg
V
V 160
160 mg
mg ++
HCTZ 25
25 mg
mg ++ "Free"
"Free" add-on
add-on
V
V 160
160 mg
mg ++ HCTZ
HCTZ
HCTZ 25
25 mg
mg
V
V 160
160 mg
mg
V
V 80
80 mg
mg
Rollover
Rollover
from
from
previous
previous therapy
therapy
A
A 55 mg
mg
(92%)
(92%)
A
A 10
10 mg
mg
A
A 10
10 mg
mg ++
HCTZ
HCTZ 12.5
12.5 mg
mg
AmlodipineAmlodipinebased
based regimen
regimen
Month
Month 0.5
0.5
00 11
22
33
Screening
Screening
Randomisation
Randomisation
*Patient
*Patient visits
visits every
every 66 months
months for
for months
months 6–72.
6–72.
Julius
Julius S
S et
et al.
al. Lancet.
Lancet. June
June 2004;363.
2004;363.
A
A 10
10 mg
mg ++
HCTZ
25
HCTZ 25 mg
mg
A
A 10
10 mg
mg ++
HCTZ
HCTZ 25
25 mg
mg ++ "Free"
"Free" add-on
add-on
44
66
**
72
72
End
End of
of treatment
treatment adjustment
adjustment period
period
Patient Population
Treated or untreated hypertensive patients
entry criteria for untreated hypertension:
160–210 mmHg systolic, 95–105 mmHg diastolic
Age ≥50 years, male or female
High-risk for cardiac events
one or more defined risk factors or diseases
Mann
Mann J,
J, Julius
Julius S.
S. Blood
Blood Press.
Press. 1998;7:176–183.
1998;7:176–183.
15,313 randomised at 942 sites in 31 countries
Average follow up 4.2 years
Julius
Julius S
S et
et al.
al. Lancet.
Lancet. June
June 2004;363.
2004;363.
Patient Characteristics
Associated
Associated Risk
Risk Factors
Factors
Increased serum
creatinine
Associated
Associated Disease
Disease Factors
Factors
3.6
LVH
LVH
6.1
12.2
Proteinuria
22.5
Active smoker
24.0
PAD
13.9
19.8
Stroke
31.6
Diabetes mellitus
33.3
High cholesterol
0
10
20
30
Patients
Patients (%)
(%)
CAD
40
45.8
0
10
20
30
40
Patients
Patients (%)
(%)
50
LVH = left ventricular hypertrophy.
PAD = peripheral artery disease; CAD = coronary artery disease.
Kjeldsen
Kjeldsen SE,
SE, Julius
Julius S
S et
et al.
al. Blood
Blood Press.
Press. 2001;10:83–91.
2001;10:83–91.
Baseline Characteristics
Variable
Valsartan
(n = 7649)
Amlodipine
(n = 7596)
Women (%)
Age (y)
3240 (42.4%)
67.2 ± 8.2*
3228 (42.5%)
67.3 ± 8.1
BMI (kg/m2)
HTN previously treated (%)
SBP (mmHg)
DBP (mmHg)
Heart rate (beats/min)
Race (%)
Caucasian
Black
Oriental
Other
28.6 ± 5.1
7088 (92.7%)
154.5 ± 19.0
87.4 ± 10.9
72.3 ± 10.8
28.7 ± 5.0
6989 (92.0%)
154.8 ± 19.0
87.6 ± 10.7
72.5 ± 10.7
6821 (89.2%)
325 (4.3%)
272 (3.6%)
231 (3.0%)
6796 (89.5%)
314 (4.1%)
261 (3.4%)
225 (3.0%)
*Mean ± SD or % of total.
Julius S et al. Lancet. June 2004;363.
VALUE:
Blood Pressure Results
Blood Pressure Changes From Baseline
to the End of the Study
00
mmHg
mmHg
–5
–5
SBP
SBP
DBP
DBP
–10
–10
–15
–15
–20
–20
Valsartan
Valsartan
Amlodipine
Amlodipine
Julius
Julius S
S et
et al.
al. Lancet.
Lancet. June
June 2004;363.
2004;363.
Systolic Blood Pressure in Study
Sitting SBP by Time and Treatment Group
mmHg
mmHg
155
155
Valsartan
Valsartan
(N=
(N= 7649)
7649)
150
150
145
145
Amlodipine
Amlodipine
(N
(N == 7596)
7596)
140
140
135
135
Baseline
Baseline
1
2
3
4
6
12
18
24
30
36
42
48
54
60
(or
(or final
final visit)
visit)
mmHg
Months
Months
5.0
5.0
4.0
4.0
3.0
3.0
2.0
2.0
1.0
1.0
00
–1.0
–1.0
66
Difference
Difference in
in SBP
SBP Between
Between Valsartan
Valsartan and
and Amlodipine
Amlodipine
1
2
3
4
6
12
18
24
Months
Months
30
36
42
48
54
60
66
(or
(or final
final visit)
visit)
Julius
Julius SS et
et al.
al. Lancet.
Lancet. June
June 2004;363.
2004;363.
Diastolic Blood Pressure in Study
Sitting
Sitting DBP
DBP by
by Time
Time and
and Treatment
Treatment Group
Group
mmHg
mmHg
90
90
Valsartan
Valsartan
(N=
(N= 7649)
7649)
85
85
Amlodipine
Amlodipine
(N
(N == 7596)
7596)
80
80
75
75
Baseline
Baseline
22
33
44
66
12
12
18
18 24
24
30
30 36
36
42
42 48
48
Months
Months
54
54 60
60
66
66
(or
(or final
final visit)
visit)
Difference
Difference in
in DBP
DBP Between
Between Valsartan
Valsartan and
and Amlodipine
Amlodipine
mmHg
mmHg
5.0
5.0
4.0
4.0
3.0
3.0
2.0
2.0
1.0
1.0
00
–1.0
–1.0
11
11
22
33
44
66
12
12
18
18 24
24
Months
Months
30
30 36
36
42
42 48
48
54
54 60
60
66
66
(or
(or final
final visit)
visit)
Julius
Julius S
S et
et al.
al. Lancet.
Lancet. June
June 2004;363.
2004;363.
Primary Endpoint Results
Primary Composite Cardiac Endpoint
Proportion of
of Patients
Patients
Proportion
With First
First Event
Event (%)
(%)
With
14
14
Valsartan-based
Valsartan-based regimen
regimen
Amlodipine-based
Amlodipine-based regimen
regimen
12
12
10
10
88
66
44
HR
HR == 1.03;
1.03; 95%
95% CI
CI == 0.94–1.14;
0.94–1.14; P
P == 0.49
0.49
22
00
0
6
12
Valsartan
7649
7459
7407
7250
7085
6906
6732
6536
6349
Amlodipine
7596
7469
7424
7267
7117
6955
6772
6576
6391
Number at risk
18 24 30 36 42 48
Time (months)
54
60
66
5911
3765
1474
5959
3725
1474
Julius
Julius S
S et
et al.
al. Lancet.
Lancet. June
June 2004;363.
2004;363.
Outcome and SBP Differences at Specific Time
Periods: Primary Endpoint
Time
Time Interval
Interval
(months)
(months)
∆
SBP
∆ SBP
mmHg
mmHg
Overall
Overall study
study
0–3
0–3
3–6
3–6
6–12
6–12
12–24
12–24
24–36
24–36
36–48
36–48
Study
Study end
end
2.2
2.2
3.8
3.8
2.3
2.3
2.0
2.0
1.8
1.8
1.6
1.6
1.4
1.4
1.7
1.7
PRIMARY
PRIMARY ENDPOINT
ENDPOINT
Odds
Odds Ratios
Ratios and
and 95%
95% CIs
CIs
0.5
0.5
Favours
Favours valsartan
valsartan
1.0
1.0
2.0
2.0
4.0
4.0
Favours
Favours amlodipine
amlodipine
Julius
Julius S
S et
et al.
al. Lancet.
Lancet. June
June 2004;363.
2004;363.
Secondary Endpoint Results
Fatal and Non-fatal Stroke
6
Proportion of
of Patients
Patients
Proportion
With First
First Event
Event (%)
(%)
With
Valsartan-based regimen
5
Amlodipine-based regimen
4
3
2
1
HR
P == 0.08
0.08
HR == 1.15;
1.15; 95%
95% CI
CI == 0.98–1.35;
0.98–1.35; P
0
0
Number at risk
6
12
18 24 30 36 42 48
Time (months)
54
60
66
Valsartan
7649 7494 7448 7312 7170 7022 6877 6692 6515 6093 3859 1516
Amlodipine
7596 7499 7455 7334 7195 7055 6918 6744 6587 6163 3846 1532
Julius
Julius S
S et
et al.
al. Lancet.
Lancet. June
June 2004;363.
2004;363.
Fatal and Non-Fatal Myocardial Infarction
Proportion of
of Patients
Patients
Proportion
With First
First Event
Event (%)
(%)
With
77
Valsartan-based
Valsartan-based regimen
regimen
Amlodipine-based
Amlodipine-based regimen
regimen
66
55
44
33
22
11
HR
HR == 1.19;
1.19; 95%
95% CI
CI == 1.02-1.38;
1.02-1.38; P
P == 0.02
0.02
00
0
Number
Number at
at risk
risk
Valsartan
Valsartan
Amlodipine
Amlodipine
6
12
18 24 30 36 42 48
Time
Time (months)
(months)
54
60 66
7649
6504 6078
1520
3864 1520
6078 3864
6680 6504
7016 6853
6853 6680
7177 7016
7319 7177
7458 7319
7499 7458
7649 7499
7596
6562 6141
1532
3840 1532
6141 3840
6727 6562
7065 6905
6905 6727
7205 7065
7332 7205
7458 7332
7497 7458
7596 7497
Julius
Julius S
S et
et al.
al. Lancet.
Lancet. June
June 2004;363.
2004;363.
Heart Failure
Hospitalisation for HF or death from HF
Proportion of
of Patients
Patients
Proportion
With First
First Event
Event (%)
(%)
With
99
88
Valsartan-based
Valsartan-based regimen
regimen
77
Amlodipine-based
Amlodipine-based regimen
regimen
66
55
44
33
22
HR
HR == 0.89;
0.89; 95%
95% CI
CI == 0.77-1.03;
0.77-1.03; P
P == 0.12
0.12
11
00
0
6
12
18 24 30 36 42 48
Time
Time (months)
(months)
54
60 66
Number
Number at
at risk
risk
Valsartan
Valsartan
7649
7649 7485
7485 7444
7444 7312
7312 7169
7169 7012
7012 6852
6852 6671
6671 6498
6498 6072
6072 3860
3860 1513
1513
Amlodipine
Amlodipine
7596
7596 7486
7486 7444
7444 7312
7312 7176
7176 7033
7033 6874
6874 6702
6702 6534
6534 6100
6100 3823
3823 1511
1511
Julius
Julius S
S et
et al.
al. Lancet.
Lancet. June
June 2004;363.
2004;363.
New-Onset Diabetes
(% of patients in
treatment group)
Incidence of New-onset Diabetes
18
23% Risk Reduction
with Valsartan
16
P < 0.0001
14
12
10
8
6
16.4%
13.1%
4
2
0
Valsartan-based
Valsartan-based Regimen
Regimen
(n
(n == 7649)
7649)
Amlodipine-based
Amlodipine-based Regimen
Regimen
(n
(n == 7596)
7596)
Julius
Julius S
S et
et al.
al. Lancet.
Lancet. June
June 2004;363.
2004;363.
Main Results
Good BP control was achieved with both treatment regimens, but BP
decrease in the amlodipine group was more pronounced, particularly
early in the trial
Despite BP differences, the primary composite cardiac endpoint in
both groups was not different
Other Results
Incidence of stroke was lower, but not significantly, in the amlodipine
group
Incidence of non-fatal MI was significantly lower in the amlodipine
group
There was a positive trend in favour of valsartan for less heart failure
but this did not reach significance
There was a highly significant lower rate of new-onset diabetes in the
valsartan group
Conclusions
Prompt blood pressure control in hypertensive patients
at high cardiovascular risk is very important
The between-group differences in heart failure and
diabetes suggest that valsartan may offer benefits
beyond BP control
Blood pressure control, and rapidity of response, are critical for
reducing events in high-risk hypertension.
2003 European Society of Hypertension - European Society of
Cardiology guidelines for the management of arterial hypertension
…...to reach target blood pressure, it is likely that a large proportion
of patients will require combination therapy with more than one
agent.
VALSARTAN/HYDROCHLOROTHIAZIDE VERSUS AMLODIPINE
ON AMBULATORY BLOOD PRESSURE
AND PLASMA NOREPINEPHRINE LEVELS IN HIGH
-RISK
HIGH-RISK
HYPERTENSIVE PATIENTS
E. Malacco et al., Advances in Therapy - Vol. 21, No. 3, 2004
Pazienti: 92 pazienti con ipertensione da lieve a moderata
(PAD≥95 mmHg e <110 mmHg) con almeno un fattore di rischio
cardiovascolare aggiuntivo.
Trattamenti: associazione valsartan 160 mg
mg ++ idroclorotiazide
idroclorotiazide
12,5 mg/die versus amlodipina 10 mg/die per 12 settimane.
Valutazioni: rilevazione clinica
e mediante monitoraggio
clinica
ambulatorio nelle 24 ore (ABPM) di PAS e PAD. Misurazione dei
livelli plasmatici di noradrenalina (NA).
Efficacia del trattamento con valsartan 160+ HCTZ12.5
vs. amlodipina 10 mg in pazienti ipertesi ad alto rischio
Amlodipina
Amlodipina 10
10 mg
mg
Valsartan
Valsartan 160
160 mg
mg ++ HCTZ
HCTZ 12.5
12.5
PAD (mmHg)
(mmHg)
∆∆ PAD
PAS (mmHg)
(mmHg)
∆∆ PAS
24
24 ore
ore
00
66 sett.
sett.
Giorno
Giorno
12
12 sett.
sett.
00
66 sett.
sett.
Notte
Notte
12
12 sett.
sett.
00
-5
-5
-5
-5
-5
-5
-10
-10
-10
-10
-10
-10
-15
-15
-15
-15
-15
-15
-20
-20
-20
-20
-20
-20
¥¥
**
¥¥
**
00
00
00
-5
-5
-5
-5
-5
-5
-10
-10
-10
-10
-10
-10
-15
-15
-15
-15
-15
-15
-20
-20
**
-20
-20
*p
*p << 0.001
0.001 -- **p
**p << 0.01
0.01 -- ¥p<0.05
¥p<0.05 vs
vs amlodipina
amlodipina
*
-20
-20
66 sett.
sett.
¥¥
12
12 sett.
sett.
**
**
¥¥
E. Malacco et al, Advances in Therapy, 2004