Come ridurre il rischio di ictus e di infarto miocardico · Department of Medicine Via Valentin...
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Transcript of Come ridurre il rischio di ictus e di infarto miocardico · Department of Medicine Via Valentin...
Paolo Verdecchia, F.E.S.C., F.A.C.C.
Hospital of Assisi. Department of Medicine
Via Valentin Müller, 1
06081 - Assisi PG
e-mail: [email protected]
Come ridurre
il rischio di ictus
e di infarto
miocardico
nell’ipertensione
arteriosa
DISCLOSURE INFORMATION
• Paolo Verdecchia
Negli ultimi due anni ho avuto i seguenti rapporti anche di finanziamento con soggetti portatori di interessi commerciali in campo sanitario:
Boehringer-Ingelheim, Bayer, BMS-Pfizer-Daiichi-Sankyo
In epidemiologia,
più bassa è la PA,
più basso è il rischio
sia di infarto
miocardico
sia di ictus cerebrale
Ischaemic
heart
disease
mortality
(floating
absolute risk
and 95% CI)
Lancet 2002; 360:1903-13
BP and Mortality from Coronary Artery Disease
The lower, the better
Systolic blood pressure Diastolic blood pressure
0
2
16
256
8
120 140 160 180
1
4
32
64
128
60-69
50-59
70-79
80-89
Age at risk (year)
0
2
16
256
8
70 80 90 110
1
4
32
64
128
60-69
50-59
70-79
80-89
Age at risk (year)
100
Usual systolic blood pressure (mmHg)
Usual diastolic blood pressure (mmHg)
40-49 40-49
Meta-analysis from 61 studies, 1 million individuals and 120 000 deaths
Systolic blood pressure
Usual systolic blood pressure (mmHg)
Stroke
mortality
(floating
absolute risk
and 95% CI)
Diastolic blood pressure
Usual diastolic blood pressure (mmHg)
Meta-analysis from 61 studies, 1 million individuals and 120 000 deaths
0
2
16
256
8
120 140 160 180
1
4
32
64
128
60-69
50-59
70-79
80-89
0
2
16
256
8
70 80 90 110
1
4
32
64
128
60-69
50-59
70-79
80-89
100
Lancet 2002; 360:1903-13
Age at risk (year)
Age at risk (year)
BP and Mortality from Stroke
The lower, the better
...ed è vera anche la
‘reverse epidemiology’:
Quanto più scende la
pressione arteriosa,
tanto più diminuisce il
rischio di eventi
cardiovascolari....
The degree of BP Reduction is a Major Determinant of
the Benefit. A meta-regression analysis
Staessen J et al.
Hypert Res 2005
The greater the
BP reduction,
the greater the
expected
benefit
(reduced risk
of events)
Effects of Antihypertensive Treatment
on CV Complications
-60
-50
-40
-30
-20
-10
0
CHF Stroke LVH CV
deaths
CHD
- 52%
- 38% - 35%
- 21% - 16%
-60
-50
-40
-30
-20
-10
0
CHF Stroke LVH CV
deaths
CHD
- 52%
- 38% - 35%
- 21% - 16%
Combined results of 17 randomized,
placebo-controlled 3- to 5-year trials.
BP decreased by 10-12/5-6 mmHg on active treatment vs placebo
Moser M et al.
J Am Coll Cardiol
1996; 27: 1214-8
Le linee-guida
fanno differenza tra
infarto e ictus? No
2016 European Guidelines on CVD Prevention in Clinical Practice. Eur Heart J 2018;37:2315-81
In alcune
‘specifiche
condizioni’
sono preferibili
alcuni tipi di
farmaci...
2016 European Guidelines on CVD Prevention in Clinical Practice.
Eur Heart J 2018;37:2315-81
Eppure c’è evidenza
che i farmaci
antiipertensivi non
sono tutti uguali nel
proteggere dall’IMA e
dall’ictus….
Verdecchia P, et al Hypertension 2005
A parità di abbassamento pressorio, gli ACE-inibitori sono
più efficaci del Calcio-antagonisti per la prevenzione
della cardiopatia coronarica
Verdecchia P, et al Hypertension 2005
A parità di abbassamento pressorio, i Calcio-antagonisti
sono più efficaci degli ACE-inibitori
per la prevenzione dell’ictus cerebrale
E questo è vero
anche per quanto
riguarda lo
scompenso cardiaco
ccongestizio…
CAPPP
ALLHAT/ACE-D
ANBP2
UKPDS39
STOP2/ACE-BB
RENAAL
LIFE
DIABHYCAR
PEACE
HOPE
TRANSCEND
EUROPA
Camelot/ACE-PLB
IDNT/ARB-PLB
PART-2
NORDIL
ALLHAT/CCB-D
STOP2/CCB-BB
INSIGHT
CONVINCE
SHELL
INVEST
ASCOT
FEVER
IDNT/CCB-PLB
ACTION
Camelot/CCB-PLB
PREVENT
SYST-China
STONE
SYST-EUR
.2
.4
.6
.8
1
1.2
1.4
1.6
1.8
2
2.2
-5 -2.5 0 2.5 5 7.5 10 -5 -2.5 0 2.5 5 7.5 10
Od
ds
Rati
o f
or
Co
ng
esti
ve H
eart
Fa
ilu
re
Systolic Blood Pressure Difference Between Randomized groups (mmHg)
ACE Inhibitors or
Angiotensin Receptor Blockers Calcium Channel Blockers
MIDAS VHAS 3.0
5.0
NICS
DREAM
Verdecchia P et al. Eur Heart J. 2009 Mar;30(6):679-88.
I sartani sono più
efficaci degli ACE-
inibitori nella
prevenzione
dell’ictus cerebrale
The risk of stroke is 8% lower with angiotensin receptor
blockers than with ACE-Inhibitors
Reboldi P, Mancia G.
Verdecchia P, et al.
J Hypertens 2008
26:1282–1289
Heterogeneity between groups: p = 0.714
Fixed Effect Model (I2 = 0.0%, p = 0.602)
ONTARGET/Tel+Ram
Random Effect Model
Random Effect Model
ELITE
Fixed Effect Model (I2 = 0.0%, p = 0.478)
ARB vs. ACEI
VALIANT/Val
VALIANT/Val+Cap
DETAIL
ARB+ACEI vs. ACEI
ELITE-II
ONTARGET/Tel
OPTIMAAL
2008
1997
2006
2006
2004
2000
2008
2002
0.92 (0.85, 0.99)
0.91 (0.81, 1.02)
0.93 (0.80, 1.07)
0.93 (0.84, 1.03)
0.91 (0.81, 1.02)
1.41 (0.31, 6.33)
0.93 (0.84, 1.03)
0.85 (0.69, 1.04)
0.87 (0.71, 1.06)
1.09 (0.34, 3.47)
1.64 (0.77, 3.48)
0.92 (0.85, 0.99)
0.91 (0.79, 1.05)
1.06 (0.83, 1.35)
1273/31632
556/13387
373/8502
4/352
717/18245
180/4909
183/4885
6/120
18/1578
369/8542
140/2744
1384/31777
616/13485
405/8576
3/370
768/18292
211/4909
211/4909
6/130
11/1574
405/8576
132/2733
Favors 1st Listed Favors 2nd Listed
Study
Publication
Year
OR
(95% CI)
Events,
ARBs
Events,
ACEi
0.5 1 2
Fixed Effect Model (I2 = 0.0%, p = 0.670)
Random Effect Model
Overall Estimate
A parità di riduzione
pressoria, l’ictus
cerebrale viene
prevenuto molto più che
l’infarto miocardico…
Il caso del diabete
mellito…
ABCD-H More vs Less
ABCD-N More vs Less
ABCD/HYP
ABCD/Norm
ACCORD BP
ACTION-Diab
ADVANCE
ALLHAT/ACE-CCB-Diab
ALLHAT/ACE-D-Diab
ALLHAT/CCB-D-Diab
ASCOT-Diab
CAPPP-Diab
DETAIL
DIABHYCAR
EUROPA-Diab
FACET
HOPE-Diab
HOT-DM More vs Less
IDNT/ARB-CCB
IDNT/ARB-PLB
IDNT/CCB-PLB
INSIGHT-Diab
INVEST-Diab
JMIC-B-Diab
LIFE-Diab MOSES-Diab
PROGRESS-Diab
RENAAL
SHEP-Diab
STOP2/ACE-BB-Diab
STOP2/ACE-CCB-Diab
STOP2/CCB-BB-Diab
SYST-EUR-Diab
UKPDS 38
UKPDS39
0.25
0.50
0.75
1.00
1.25
1.50
1.75
2.00
2.25
2.50
2.75 3.00
Re
lati
ve
Ris
k o
f S
tro
ke
-4 -2 0 2 4 6 8 10
Diastolic BP difference between randomised groups, mmHg
ABCD/HYP
FACET UKPDS 38
UKPDS39
STOP2/CCB-BB-Diab
ABCD-H More vs Less
STOP2/ACE-CCB-Diab
STOP2/ACE-BB-Diab
ATLANTIS/1.25
ATLANTIS/5
HOPE-Diab
HOT-DM More vs Less
CAPPP-Diab
RENAAL
ABCD/Norm
LIFE-Diab
ABCD-N More vs Less
IDNT/ARB-CCB
IDNT/ARB-PLB
IDNT/CCB-PLB
JMIC-B-Diab
DETAIL
INVEST-Diab
DIABHYCAR EUROPA-Diab
ADVANCE
ASCOT-Diab ACCORD BP
ACTION-Diab
0.25
0.50
0.75
1.00
1.25
1.50
1.75
2.00
2.25
2.50
2.75 3.00
Re
lati
ve
Ris
k o
f A
cu
te M
yo
ca
rdia
l In
farc
tio
n
-4 -2 0 2 4 6 8 10
Reboldi GP, Verdecchia P, Angeli F et al,
Journal of Hypertension, 2011
SPRINT
Hazard Ratio = 0.75 (95% CI: 0.64 to 0.89)
Standard
Intensive (243 events)
Median follow-up = 3.26 years Number Needed to Treat (NNT) to prevent a primary outcome = 61
SPRINT: Primary Outcome
(319 events)
Come porre lo studio
SPRINT nel contesto
degli altri studi di
confronto tra target
pressori diversi?
Verdecchia P et al. Hypertension 2016; 68: 642-53
Verdecchia P et al. Hypertension 2016; 68: 642-53
Circulation Research 2017;120:27-29
Grazie per la vostra attenzione
Knot at -34 mmHg
1.05 (0.91-1.21)
p=0.5124
Knot at 20 mmHg
1.20 (1.06-1.35)
p=0.0032
Knot at -7 mmHg
Reference
Wald
Chi-Square DF p-value
Nonlinear 5.7432 1 0.0166
Knot at -34 mmHg
0.84 (0.71-0.99)
p=0.0456
Knot at 20 mmHg
1.42 (1.23-1.63)
p<0.0001
Knot at -7 mmHg
Reference
Wald
Chi-Square DF p-value
Nonlinear 2.5093 1 0.1132
Knot at -21 mmHg
1.09 (0.96-1.25)
p=0.2021 Knot at 10 mmHg
1.04 (0.97-1.12)
p=0.2887 Knot at -6 mmHg
Reference
Wald
Chi-Square DF p-value
Nonlinear 3.6899 1 0.0547
Knot at -21 mmHg
0.79 (0.67-0.93)
p=0.0049
Knot at 10 mmHg
1.18 (1.12-1.23)
p<0.0001
Wald
Chi-Square DF p-value
Nonlinear 1.0419 1 0.3074
Knot at -6 mmHg
Reference
Conclusions. In patients with CAD and initially free from CHF, a BP reduction from baseline over the examined BP range
had little effect on the risk of MI and predicted a lower risk of stroke. An increase in SBP from baseline increased the risk
of stroke and MI. A treatment-induced BP reduction over the explored range was safe in these patients.
Verdecchia P et al. Hypertension. 2015;65:108-14
Il risultato non cambia anche considerando
i valori pressori ‘assoluti’.....