Curiosare tra le raccomandazioni delle nuove linee guida ... · linee guida sull’ipertensione arteriosa Stefano Taddei Dipartimento di Medicina Clinica e Sperimentale ... Criteri

Curiosare tra le raccomandazioni delle nuove

linee guida sull’ipertensione arteriosa

Stefano Taddei Dipartimento di Medicina Clinica e Sperimentale

Università di Pisa

2013 ESH/ESC Hypertension Guidelines

2003 Guidelines

2007 Guidelines

2009 Reappraisal ESH

2013 Guidelines

J Hypertens 2013;31:1281-1357

Eur Heart J 2013 June 14

Blood Pressure 2013 June 15

Historical Perspective

Table of contents


1. Introduction

2. Epidemiological aspects

3. Diagnostic evaluation

4. Treatment approach

5. Treatment strategies

6. Treatment strategies in special conditions

7. Treatment of associated risk factors

8. Follow-up

9. Improvement of blood pressure control in hypertension

10. Hypertension disease management

11. Gaps in evidence and need for future trials

Appendix 1

Appendix 2

Acknowledgements

References

Table of contents


1. Introduction

2. Epidemiological aspects

3. Diagnostic evaluation

4. Treatment approach

5. Treatment strategies

6. Treatment strategies in special conditions

7. Treatment of associated risk factors

8. Follow-up

9. Improvement of blood pressure control in hypertension

10. Hypertension disease management

11. Gaps in evidence and need for future trials

Appendix 1

Appendix 2

Acknowledgements

References


Threshold BP

Target BP

General hypertensive

population

≥ 140/90 mmHg

< 140/90 mmHg

High / very high CV risk

(DM / CVD / CKD)

≥ 130/80 mmHg

< 130/80 mmHg

BP threshold / targets flexible according to CV risk level

142

137

149

138

150

146

140

130

148

130

100

110

120

130

140

150

160

Achieved SBP in “Uncomplicated” HypertensionS

BP

(m

mH

g)

OS HDFP AUS MRC FEV

BP ∆Benefit

Zanchetti, Grassi, Mancia J Hypert 2009; 27: 923 - Mancia et al., J Hypert 2009; 27: 2121

%

130

110

100

120

140

150

160

Achieved SBP in Trials

Zanchetti, Grassi, Mancia, J Hypertens 2009; 27: 923-934, Mancia et al., J Hypertens 2009; 27: 2121

133

119

141

143

140

128132

134134

153

139

144145145

110

120

130

140

150

160

170

Diabetes

HOT

SHEP

UKPDS S. Eur ADV ABCD

RENHOPEAM

IDNT

ACRD

NAV

preDM

Benefit No benefit

SB

P (

mm

Hg

)

Active treatment

PROG

HT NT

IDNT


Zanchetti, Grassi, Mancia, J Hypertens 2009; 27: 923-934, Mancia et al., J Hypertens 2009; 27: 2121

133

119

141

143

140

128132

134134

153

139

144145145

110

120

130

140

150

160

170

129

124

130

122

136

124

128

135136

150

132

143

100

110

120

130

140

150

160

Diabetes Previous CVD

PATS

PROG

ACC

PROF

HOPE

EU

CAM-AM PREV

ACT

CAM-EN

PEATR

Stroke CHD

HOT

SHEP

UKPDS S. Eur ADV ABCD

RENHOPEAM

IDNT

SB

P (

mm

Hg

)ACRD

NAV

preDM

Benefit No benefit

SB

P (

mm

Hg

)

Benefit No benefit Benefit No benefit

Active treatment

Active treatment

PROG

HT NT

IDNT

Target SBP < 130 mmHg at high / very high CV risk


• No clear / consistent evidence of CV event reduction also by

subgroup / post-hoc data analysis

• No beneficial effects on risk of ESRD in nephropathic patients

• Although mainly based on post-hoc approach, suspicion of a possible

J curve phenomenon

Blood pressure goals in hypertension

2013 ESH/ESC Hypertension Guidelines2013 ESH/ESC Hypertension Guidelines

• A SBP < 140 mmHg recommended/considered, regardless the level of

risk

• Low/moderate risk (IB)

• Diabetes (IA)

• Diabetic/nondiabetic CKD (IIaB)

• Patients with CHD/previous stroke or TIA (IIaB)

• A DBP < 90 mmHg recommended

Elderly patients

(> 65 - < 80 Years)

Elderly patients

(> 65 - < 80 Years)

Per quali livelli di pressione arteriosa è

raccomandato iniziare il trattamento?

Recruitment BP criteria Mean BP at randomization

Trial SBP

(mmHg)

DBP

(mmHg)

SBP

(mmHg)

DBP

(mmHg)

EWPHE 160-239 or 90-119 183 101

Coope/warrende

r

>170 or >105 196 99

SHEP >160 and <90 170 77

STOP-1 >180 or >105 195 94

MRC-elerly 160-209 and <115 185 91

Syst-Eur 160-219 and <95 174 85

Syst-China 160-219 and <95 171 86

SCOPE* 160-179 or 90-99 166 90

HYVET 160-179 and <110 173 91

YATOS >160 and <120 171 89

*In SCOPE 50% of patients pretreated with low dose thiazides

Zanchetti, Grassi, Mancia, J Hypertens 2009; 27: 923-934

BP at randomization in antihypertensive treatment trials in th elderly


Elderly patients with SBP < 160 mmHg represent a

relevant number in trials showing beneficial effects of

antihypertensive drug treatment

Elderly hypertensive patients


In ELDERLY HYPERTENSIVE PATIENTS drug treatment

• is recommended when SBP ≥ 160 mmHg

• may be considered (in those aged < 80 years) if SBP 140-

159 mmHg, provided treatment is well tolerated

Evidence

Class Level

I A

IIb C

Elderly patients

(> 65 - < 80 Years)

Quali livelli di pressione arteriosa è

raccomandato raggiungere con il

trattamento?


18559a M Zanchetti, Grassi, Mancia, J Hypertens 2009; 27: 923-934, Mancia et al., J Hypertens 2009; 27: 2121

138

145144

151151

156

167

143

162

150

120

130

140

150

160

170

180

190

ElderlyS

BP

(m

mH

g)

EW SHEP MRC S. China SCOPE

CW STOP S. Eur HYVET

JATOS

Benefit No benefit

Active treatment

Incidence of Morbidity / Mortality in HYVETN

o.

of

eve

nts

pe

r 1

00

pa

tie

nts

Total mortality

Fatal stroke

Heart failure

All stroke

0 1 2 3 4

Follow-up (yr)

0 1 2 3 4

Follow-up (yr)

0

1

2

3

4

5

6

7

8

0

1

2

3

4

5

0

10

20

30

1

2

3

4

5

6

7

Placebo

173/91 → 160/84 (mmHg)

Active treatment

173/91 → 144/78 (mmHg)

-30%-39%

-21%-64%p < 0.0001 p = 0.019

p = 0.055 p = 0.046

Goal SBP < 150 mmHg

HYVET - Beckett, NEJM 2008; 358: 10

Target BP in the elderly


• In elderly pts (>65 ys of age) there is solid evidence to recommend

reducing SBP to 150-140 mmHg (IA)

• This is the case also in individuals older than 80 ys, provided they are

in good physical/mental conditions

• Any evidence in favour of lower BP targets?

BP targets in the elderly


“In fit elderly pts <80 ys old a SBP TARGET <140mmHg may be

considered if treatment is well tolerated”

Evidence

Class Level

IIb CC

Choice of antihypertensive drugs -

Conclusions from 2013 (and 2003 and 2007) Guidelines


• The main benefits of antihypertensive treatment are due to lowering BP “per se” and

are largely independent of the drug employed

• Although meta-analyses occasionally claim superiority of one class for some

outcomes this largely depends on selection bias of trials. The largest meta-analyses

do not show clinically relevant between-class differences

Choice of antihypertensive drugs -

Conclusions from 2013 (and 2003 and 2007) Guidelines


• The main benefits of antihypertensive treatment are due to lowering BP “per se” and

are largely independent of the drug employed

• Although meta-analyses occasionally claim superiority of one class for some

outcomes this largely depends on selection bias of trials. The largest meta-analyses

do not show clinically relevant between-class differences

• Current Guidelines reconfirm that the following drugs classes are all suitable for

initiation and maintenance of antihypertensive treatment either as monotherapy or

in some combinations with each other (IA)

• Diuretics (thiazides / chlorthalidone / indapamide)

• Beta-blockers

• Calcium antagonists

• ACE-inhibitors

• Angiotensin receptor blockers

Algoritmo BHS/NICE (UK)

NICE/BHS, www.bhsoc.org 2006

Van Vark C et al, Eur Heart 2011

Effect of ACE-I and ARBs on total mortality

(158.998 patients)

Van Vark C et al, Eur Heart 2011

Effect of ACE-I and ARBs on total mortality

(158.998 patients)

Effect of ACE-Is or ARBs on outcomes

(108.212 patients)

Composite outcome

%

0,11

0,7

0,5

0,9

Cardiovascular death

%

0,11

0,7

0,5

0,9

Myocardial infarction

%

0,11

0,7

0,5

0,9

New heart failure onset

%

0,11

0,7

0,5

0,9

All-cause death

%

0,11

0,7

0,5

0,9

Stroke

%

0,11

0,7

0,5

0,9*

** *

*

New diabetes onset

%

0,11

0,7

0,5

0,9

*

** *

Savarese G et al, JACC 2013

ACE-Is

ARBs

outcome significantly reduced as compared to placebo*

Composite outcome

%

0,11

0,7

0,5

0,9

Cardiovascular death

%

0,11

0,7

0,5

0,9

Myocardial infarction

%

0,11

0,7

0,5

0,9

New heart failure onset

%

0,11

0,7

0,5

0,9

All-cause death

%

0,11

0,7

0,5

0,9

Stroke

%

0,11

0,7

0,5

0,9*

** *

*

New diabetes onset

%

0,11

0,7

0,5

0,9

*

** *

Savarese G et al, JACC 2013

ACE-Is

ARBs

outcome significantly reduced as compared to placebo*

Effect of ACE-Is or ARBs on outcomes

(108.212 patients)

Drugs to be preferred in specific conditions


2007 ESH/ESC Guidelines

Criteri di scelta tra monoterapia e terapia di associazione

Scegliere tra

Se non si riesce ad ottenerel’obiettivo pressorio


Monoterapia a basso dosaggio

Associazione di 2 farmaci a basso dosaggio

Associare tra loro tre farmaci a dosaggio pieno

Raggiungere il dosaggio pieno

Modifica del farmaco iniziando a basso

dosaggio

Raggiungere il dosaggio pieno dell’associazione

Aggiungere un terzo farmaco a basso

dosaggio

Associare tra loro 2-3 farmaci a dosaggio

pieno

Monoterapia a dosaggio pieno

Lieve incremento pressorioRischio CV basso/moderato

Obiettivo pressorio convenzionale

Marcato incremento pressorio

Rischio CV elevato o molto elevato

Obiettivo pressorio piùambizioso

22

2007 ESH/ESC Guidelines

Criteri di scelta tra monoterapia e terapia di associazione

Scegliere tra



Monoterapia a basso dosaggio

Associazione di 2 farmaci a basso dosaggio

Associare tra loro tre farmaci a dosaggio pieno

Raggiungere il dosaggio pieno

Modifica del farmaco iniziando a basso

dosaggio

Raggiungere il dosaggio pieno dell’associazione

Aggiungere un terzo farmaco a basso

dosaggio

Associare tra loro 2-3 farmaci a dosaggio

pieno

Monoterapia a dosaggio pieno

Lieve incremento pressorioRischio CV basso/moderato

Obiettivo pressorio convenzionale

Marcato incremento pressorio

Rischio CV elevato o molto elevato

Obiettivo pressorio piùambizioso

Associazioni “omeopatiche”

Ramipril 2.5 mg / HTCZ 12.5 mg

Perindopril 2.5 mg / Indapamide 0.625

Incremento dose

monoterapia

Monotherapy vs. drug combination strategies

to achieve target BP


Possible combinations of antihypertensive drug classes


Only dihydropyridines to be combined with β-blockers (except for verapamil or diltiazem for rate control in AF)

Thiazides + β-blockers increase risk of new onset DM

ACEI + ARB combination discouraged (IIIA)

Green/continuous: preferred

Green/dashed: useful (with some limitations)

Black/dashed: possible but less well tested

Red/continuous: not recommended

Meccanismi d’ azione dei farmaci antipertensivi

Diuretici

Calcio antagonisti

Alfa-antagonistiSRA

ACE-inibitori

AT-1 antagonisti

Beta-bloccanti

Vasodilatatori SNSACE-inibitori

AT-1 antagonisti

Beta-bloccanti

Simpatomodulatori

VALUE: Disegno dello Studio

Titolazione secondo target pressorio (<140/90 mmHg)

Mese 0.5 0 1 2 3 4 6 * 72

A 10 mg +

HCTZ 25 mg

A 5 mg

A 10 mg +

HCTZ 12.5 mg

A 10 mg

V 80 mg

V 160 mg

V 160 mg +

HCTZ 12.5 mg

V 160 mg +

HCTZ 25 mg

Terapia a base di

Amlodipina

V 160 mg +

HCTZ 25 mg + Agg. “libera"

A 10 mg +

HCTZ 25 mg + Agg. “libera"

Terapia a base di

Valsartan

ScreeningRandomizzazione Fine della fase di

aggiustamento posologico

Randomizzazione

(Pazienti già in

trattamento 92%)

*Visite ai pazienti ogni 6 mesi per 6–72 mesi.

Julius S et al. Lancet. 2004

Andamento della Pressione Arteriosa

Valsartan

(N= 7649)

Amlodipina

(N = 7596)

135

140

145

150

155

mm

Hg

Mesi (o visita finale)

PAS nel tempo, per gruppo di trattamento

Basale 1 24 482 3 4 6 12 18 30 36 42 54 60 66

Julius S et al. Lancet. Giugno 2004;363.

Valsartan

(N= 7649)

Amlodipina

(N = 7596)

mm

Hg

(o visita finale)

PAD nel tempo, per gruppo di trattamento

Basale 1 24 482 3 4 6 12 18 30 36 42 54 60 66

75

85

80

90

4.3 mmHg

2.5 mmHg

100

105

110

115

120

PA

me

dia

Placebo Nifedipina Clortalidone Nifedipina+

Clortalidone

107.3±1.2

108.9±0.9108.4±1.1

117.5±1.5

****

*

* p <0.05 vs placebo

Assenza di effetto additivo tra i

Calcio-Antagonisti e i Diuretici

Salvetti et al, J Hypertens 1989

ALLHAT Study

Farmaco

Clortalidone

Amlodipina

Lisinopril

Associazione

Atenololo

Atenololo

Atenololo

Razionale

Razionale

Non razionale

Nello studio ALLHAT il controllo della PA è stato inferiore nel braccio trattato con lisinopril!

RAS Blocker plus CA or Diuretic (D) in ACCOMPLISH


• Only trial comparing two combinations in all patients

• ACEI+D inferior to ACEI+CA despite no BP difference

• Replication desirable because trials on CA-based vs D-based therapy

have never shown a CA superiority

• Further information on which patients benefit more from one or the

other treatment extremely important

Applicazione delle Linee Guida nella

pratica clinica quotidiana

1. Le Linee Guida sono un discreto strumento culturale (un “text book” sull’

ipertensione)

2. La gestione del paziente deve però essere affidata alle qualità cliniche

del medico che sono determinate dalla sapiente unione di: cultura,

esperienza e buon senso.

Curiosare tra le raccomandazioni delle nuove linee guida ... · linee guida sull’ipertensione arteriosa Stefano Taddei Dipartimento di Medicina Clinica e Sperimentale ... Criteri

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