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: verdec@tin.it

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’.....