hipertensión arterial 2014: de las guías a la práctica clínica - dr. josé r. gonzález juanatey

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Presentación del Dr. José R. González Juanatey, del Hospital Clínico Universitario de Santiago, durante la I Reunión de Denervación Renal de la Sección de Hemodinámica y Cardiología Intervencionista (SHCI) de la Sociedad Española de Cardiología (SEC), celebrada del 29 al 30 de enero de 2014.

TRANSCRIPT

J.R.G. JUANATEY C.H.U.Santiago

José R. González Juanatey Área Cardiovascular. Hospital Clínico Universitario de Santiago de

Compostela

Hipertensión Arterial 2014

De las Guías a la Práctica Clínica

J.R.G. JUANATEY C.H.U.Santiago

HTA- 2014. Nuevas Guías

Aspectos Epidemiológicos

Las Nuevas Guías y la Evaluación del Riesgo

Las Nuevas Guías y los Objetivos Terapéuticos

Las Nuevas Guías y la Selección de Fármacos

J.R.G. JUANATEY C.H.U.Santiago

Epidemiología HTA

.30 – 45 % de la población adulta (> 1.500 millones personas)

J.R.G. JUANATEY C.H.U.Santiago

World’s biggest killers – CVD

retain top spot

J.R.G. JUANATEY C.H.U.Santiago

Contribución de la mortalidad CV a la esperanza

de vida en España de 1980 a 2009

García González JM, et al. Rev Esp Cardiol 2013. on line

Mujeres 1980-2009 Varones 1980-2009

Estilo de Vida Prevención

Organización asistencial Tratamiento

INCORPORACIÓN INNOVACIÓN

J.R.G. JUANATEY C.H.U.Santiago

HTA- 2014. Nuevas Guías

Aspectos Epidemiológicos

Las Nuevas Guías y la Evaluación del Riesgo

Las Nuevas Guías y los Objetivos Terapéuticos

Las Nuevas Guías y la Selección de Fármacos

J.R.G. JUANATEY C.H.U.Santiago

HTA consulta y ambulatoria mmHg

Categoría PA sistólica PA diastólica

Consulta ≥ 140 y/o ≥ 90

MAPA

Día (actividad) ≥ 135 y/o ≥ 85

Noche (reposo) ≥ 120 y/o ≥ 70

24 horas ≥ 130 y/o ≥ 80

AMPA ≥ 135 y/o ≥ 85

JNC VIII / ASH ESC / ESH 2013

J.R.G. JUANATEY C.H.U.Santiago

EVALUATING THE PATIENT History. Important previous events include: Stroke, TIA, CAD, HF or symptoms of left vemtricular dysfunction, CKD, Pripheral artery disease, Diabetes, Sleep apnea, ask about other risk factors and concurrent drugs.

Physical Examination. Measuring BP; weight, height and BMI, waist circumference, signs of HF, neuro examination, optic fundi (if possible), peri-ocular xantomas, peripheral pulses.

TESTS Blood Sample: electrolytes, Fasting glucose, serum creatinine and BUN, Lipids, Hb/hematocrit, liver function tests.

Urine Sample: Albuminuria, red and white cells.

ECG. All patients

ECHOCARDIOGRAM. , if available, can be helpful …., although this test is not routine in hypertensive patients

2013

J.R.G. JUANATEY C.H.U.Santiago

Medication CV predictive value Availability Reproducibility Cost-effect

ESC/ESH 2013.

Guidelines Markers of organ damage

J.R.G. JUANATEY C.H.U.Santiago

Factores de riesgo (FRCV)

Lesión de órgano diana (LOD)

Enfermedad cardiovascular (ECV)

No otros factores de riesgo

1 – 2 factores de riesgo

≥ 3 factores de riesgo

LOD, IRC 3 o Diabetes

ECV sintomática, IRC ≥ 4 o Diabetes con LOD/FRCV

Presión arterial (mmHg)

Normal alta PAS 130 – 139 o PAD 85-89

HTA grado 1 PAS 140 – 159 o PAD 90-99

HTA grado 2 PAS 160 – 179 o PAD 100-109

HTA grado 3 PAS ≥ 180

o PAD ≥ 110

Bajo riesgo

Bajo riesgo

Alto riesgo

Alto riesgo

Alto riesgo

Alto riesgo

Alto riesgo

Alto riesgo

Muy alto riesgo Muy alto riesgo Muy alto riesgo Muy alto riesgo

Moderado riesgo

Moderado riesgo Moderado a alto riesgo

Moderado a alto riesgo

Alto a muy alto riesgo

Bajo a moderado riesgo

Moderado a alto riesgo

JNC VIII / ASH ESC / ESH 2013

J.R.G. JUANATEY C.H.U.Santiago

HTA- 2014. Nuevas Guías

Aspectos Epidemiológicos

Las Nuevas Guías y la Evaluación del Riesgo

Las Nuevas Guías y los Objetivos Terapéuticos

Las Nuevas Guías y la Selección de Fármacos

J.R.G. JUANATEY C.H.U.Santiago

JNC VIII / ASH ESC / ESH 2013

JAMA 2013 / AJH 2013

Eur Heart J / J Hypertens 2013

< 140/90 mmHg

< 140/90 mmHg in

diabetes and chronic

renal failure

“…it may be prudent to

recommend lowering

SBP/DBP to values < 140/90

mmHg in all hypertensive

patients…” “…<140/85

mmHg in diabetes…”

J.R.G. JUANATEY C.H.U.Santiago

Objetivos Terapéuticos en Pacientes con HTA

Recomendaciones Clase Nivel

Presión arterial sistólica < 140 mmHg

pacientes con riesgo cardiovascular bajo-moderado I B

pacientes con diabetes I A

pacientes con ictus previo o ataque isquémico transitorio IIa B

pacientes con cardiopatía isquémica IIa B

pacientes con insuficiencia renal, diabética o no diabética IIa B

Ancianos (< 80 años) con PAS ≥ 160 mmHg, objetivo PAS entre 140 y 150

mmHg

I A

Ancianos (< 80 años) en buena forma física < 140 mmHg IIb C

Ancianos (> 80 años) con PAS ≥ 160 mmHg, objetivo PAS entre 140 y 150

mmHg, si están en buenas condiciones

I B

Presión arterial diastólica < 90 mmHg; en diabéticos < 85 mmHg. Valores

PAD 80-85 mmHg son seguros y bien tolerados

I A

ESC / ESH 2013

J.R.G. JUANATEY C.H.U.Santiago

Patients BP

Adults Aged > 18 y > 140 / 90 mmHg OBP

Age > 80 y > 150 / 90 mmHg OBP

High Risk (DM, CKD) > 140 / 90 mmHg OBP

2013 Blood Pressure >140/90 in Adults Aged >18 years

(For age >80 years, pressure >150/90 or >140/90 if high risk (DM, CKD

Start Lifestyle Changes (Lose weight, reduce dietary salt and alcohol, stop smoking)

J.R.G. JUANATEY C.H.U.Santiago

Recommendation 1 In the general population aged 60 years or older, initiate pharmacologic treatment to lower BP at SBP of 150 mm Hg or higher or DBP of 90 mm Hg or higher and treat to goal SBP lower than 150 mm Hg and goal DBP lower than 90 mm Hg. Strong recommendation – Grade A

Recommendation 2 In the general population younger than 60 years initiate pharmacologic treatment to lower BP at DBP of 90 mm Hg or higher and treat to goal DBP of lower than 90 mm Hg For ages 30-59 years: Strong recommendation – Grade A For ages 18-29 years: Expert opinion – Grade E

Recommendation 3 In the general population younger than 60 years initiate pharmacologic treatment to lower BP at SBP of 140 mm Hg or higher and treat to goal SBP of lower than 140 mm Hg Expert opinion – Grade E

J.R.G. JUANATEY C.H.U.Santiago

Metaregression of Treatment-induced Systolic BP Changes with Stroke and Myocardial Infarction

Reboldi, Gentile, Angeli, Ambrosio, Mancia, Verdecchia, 2010

Stroke Myocardial

infarction

3.00 2.75 2.50 2.25

2.00

1.75

1.50

1.25

1.00

0.75

0.50

0.25

Rel

ativ

e ri

sk

SBP difference between randomized groups (mmHg)

-6 -4 -2 0 2 4 6 8 10 12 14 16 18 20 -6 -4 -2 0 2 4 6 8 10 12 14 16 18 20

3.00 2.75 2.50 2.25

2.00

1.75

1.50

1.25

1.00

0.75

0.50

0.25

ABCD-N More vs Less

SYST-EUR Diab

ACCORD BP UKPDS 38

FACET

MOSES-Diab

JMIC-B-Diab

HOPE-Diab IDNT/CCB -PLB

PROGRESS-Diab

SHEP-Diab

EUROPA-Diab

ABCD-H

More vs Less

ACTION-Diab

ABCD/Norm

ABCD/HT

IDNT/ARB-CCB

IDNT/ARB-PLB

ADVANCE

ASCOT-Diab

HOT-DM More vs Less

DETAIL

DETAIL

ALLHAT/ACE-CCB-Diab

STOP2/CCB-BB-Diab

LIFE-Diab INVEST-Diab

IINSIGHT-Diab ALLHAT/CCB-D-Diab

STOP2/ACE-BB-Diab RENAAL

DIABHYCAR CAPPP-Diab ALLHAT/ACE-D-Diab

UKPDS 39 STOP2/ACE-CCB-Diab

ABCD-N More vs Less

ACCORD BP

UKPDS 38

FACET

JMIC-B-Diab

HOPE-Diab

IDNT/ARB-CCB

EUROPA-Diab

ACTION-Diab

ABCD/Norm

ABCD/HT

IDNT/ARB-CCB

IDNT/ARB-PLB

ADVANCE

ASCOT-Diab

HOT-DM More vs Less

DETAIL STOP2/CCB-BB-Diab

LIFE-Diab

INVEST-Diab

STOP2/ACE-BB-Diab

RENAAL

DIABHYCAR

CAPPP-Diab

UKPDS 39

STOP2/ACE-CCB-Diab

ATLANTIS/1.25

ATLANTIS/5

ABCD-H More vs Less

J.R.G. JUANATEY C.H.U.Santiago

CV Event Incidence in Relation to Mean FU Systolic BP (up to 1st event) in VALUE

Mancia et al., 2010

MI Stroke

0

4

8

12

16

20

0

2

4

6

8

10

2.21 1.76 2.64

4.03

6.81

9.36

11.72

17.42

4.92

3.93

3.27

4.51

6.97

8.18 8.70

5.43

<120

120-

<130

130-

<140

140-

<150

150-

<160

160-

<170

170-

<180

≥180

SBP (mmHg)

<120

120-

<130

130-

<140

140-

<150

150-

<160

160-

<170

170-

<180

≥180

SBP (mmHg)

% %

J.R.G. JUANATEY C.H.U.Santiago

Incidence and Unadjusted CV Risk of Events

in Deciles of In-treatment SBP

Un

adju

sted

ris

k o

f ev

ents

(%

)

HR

(95% C

I) On-treatment SBP (mmHg)

Un

adju

sted

ris

k o

f ev

ents

(%

)

HR

(95% C

I)

Myocardial infarction Stroke

Sleight, et al., J Hypert 2009; 27: 1360-1369

112 121 126 130 133 136 140 144 149 160

0

5

10

0

1

2

112 121 126 130 133 136 140 144 149 160 0

5

10

0

2

4

6

On-treatment SBP (mmHg)

J.R.G. JUANATEY C.H.U.Santiago

Risk of coronary events in people with CKD Compared with

diabetes: a population-level Cohort study

Tonelli M, et al. Lancet 2012; 380:807-812;

Polonsky-Bakris. Lancet 2012; 380:783-785.

J.R.G. JUANATEY C.H.U.Santiago

Recommendation 4

In the population aged 18 years or older with CKD, initiate pharmacologic treatment to lower BP at SBP of 140 mm Hg or higher or DBP of 90 mm Hg or higher and treat to goal SBP of lower than 140 mm Hg and goal DBP lower tan 90 mm Hg Expert opinion – Grade E

Recommendation 5

In the population aged 18 years or older with Diabetes, initiate pharmacologic treatment to lower BP at SBP of 140 mm Hg or higher or DBP of 90 mm Hg or higher and treat to goal SBP of lower than 140 mm Hg and goal DBP lower tan 90 mm Hg Expert opinion – Grade E

Recommendation 6 In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, CCB, ACEi or ARB Moderate Recommendation – Grade B

J.R.G. JUANATEY C.H.U.Santiago

lower diastolic pressure

higher LV end-diastolic pressure

reduced coronary

perfusion in diastole

cardiovascular disease

healthy

J.R.G. JUANATEY C.H.U.Santiago

¿Curva “J” o Relación Lineal entre PA e IAM?

100%

50%

0%

Rie

sg

o

Presión Arterial

J.R.G. JUANATEY C.H.U.Santiago

CV outcomes from the ACCOMPLISH trial

OUTCOMES: (MI, stroke, revascularization, all-cause mortality)

Weber M, et al. Am J Med 2013

J.R.G. JUANATEY C.H.U.Santiago

ESC/ESH 2013.

J.R.G. JUANATEY C.H.U.Santiago

Recomendaciones Clase Nivel evidencia en

reducción de PA y riesgo

cardiovascular

Nivel evidencia en

reducción de eventos

clínicos

Consumo de sal: 5-6 g/día I A B

Moderar el consumos de alcohol

(< 20-30 g/día etanol en hombres,

< 10-20 g/día mujeres)

I A B

Aumento del consumo de verdura, fruta y

productos bajos en grasa

I A B

Reducir el peso a IMC: 25 kg/m2, perímetro

abdominal < 102 cm en hombres y < 88 cm

en mujeres

I A B

Ejercicio físicos regular, dinámico,

≥ 30 min/día, 5-7 días/semana

I A B

Aconsejar y ofrecer asistencia a los

fumadores para dejar el tabaco

I A B

Tratamiento de la HTA. Cambios en el estilo de vida

J.R.G. JUANATEY C.H.U.Santiago

HTA- 2014. Nuevas Guías

Aspectos Epidemiológicos

Las Nuevas Guías y la Evaluación del Riesgo

Las Nuevas Guías y los Objetivos Terapéuticos

Las Nuevas Guías y la Selección de Fármacos

J.R.G. JUANATEY C.H.U.Santiago

PA Efectos favorables

sobre otros FR /

Marcadores inflamatorios

Prevención NDM

Prevención HTA

Ictus

IC

EAC / IM

ERT

Regresión /

prevención LOD

HVI

Engrosamiento arterial / placas

Proteinuria / microalbuminuria

Rigidez arterial

Remodelado arteriolar

Reducción TFG / CrS

Disfunción endotelial

Ca++ coronario

Enf. cerebral lacunar / LSB

Retinopatía

Fibrosis cardíaca (marcadores colágeno)

Deterioro cognitivo / Demencia

Prevención FA

J.R.G. JUANATEY C.H.U.Santiago

ESC/ESH 2013 Guidelines.

Combinations of classes of anti-hypertensive drugs

Thiazide diuretics

Beta-blockers Angiotensin R

blockers

Calcium

antagonists

ACE inhibitors

Other

Antihypertensives

J.R.G. JUANATEY C.H.U.Santiago

Initial Combinations of Medications*

Thiazide-Like Diuretics

ACE inhibitors

or

ARBs

Calcium

antagonists

Beta-blockers should be included in the regimen if there is a compelling indication for a beta-blocker

J.R.G. JUANATEY C.H.U.Santiago

Reducción Media de la PA de 24 Horas (Pico y Valle) en

357 Estudio Randomizados (n = 40000 pacientes Tratados y 16000 Placebo)

Law MR et al., Brit Med J 2003; 326: 1427

Half standard Standard Twice standard

-12

-9

-6

-3

Thiazides Beta-blockers ACEI ARB CA

Half standard Standard Twice standard

-9

-6

-3

0

P

AS

(m

mH

g)

P

AD

(m

mH

g)

J.R.G. JUANATEY C.H.U.Santiago

Efectos Adversos de Fármacos en 357 Estudios Randomizados (n = 40000 Pacientes Tratados y 16000 Placebo)

Law MR et al., Brit Med J 2003; 326: 1427

Half standard Standard Twice standard-5

0

5

10

15

20

Thiazides

Beta-blockers

ACEI

ARB

CA

%

Wald DS et al., Am J Med 2009; 122: 290

Inc

rem

en

tal S

BP

re

du

cti

on

ra

tio

of

ob

se

rve

d t

o e

xp

ec

ted

ad

dit

ive

eff

ec

ts

* The expected incremental effect is the incremental blood pressure reduction of the added (or doubled drug), assuming

an additive effect and allowing for the smaller reduction from 1 drug (or dose of 1 drug) given the lower pretreatment

blood pressure because of the other

1.5

1.0

0.5

0.0

Adding a drug from

another class (on

average standard

doses)

Doubling dose of same

drug (from standard

dose to twice standard)

1.04

(0.88-1.20)

1.00

(0.76-1.24)

1.16

(0.93-1.39)

0.89

(0.69-1.09)

1.01

(0.90-1.12)

0.19

(0.08-0.30)

0.23

(0.12-0.34) 0.20

(0.14-0.26)

0.37

(0.29-0.45)

0.22

(0.19-0.25)

Thiazide Beta-

blocker

ACE-

inhibitor

Calcium channel

blocker

All

classes

Combination therapy is more effective than doubling

the dose

J.R.G. JUANATEY C.H.U.Santiago

Multiple Medication Are Required to Achieve BP

Control in Clinical Trials

Hypertension

Diabetes

Kidney

Disease

J.R.G. JUANATEY C.H.U.Santiago

Guía ESH/ESC 2013

Tratamiento Farmacológico Inicial

Decidir entre

ESH/ESC Guidelines. J Hypertens 2013

Elevación ligera de PA

Objetivo de PA < 140/90 Elevación marcada de PA

Combinación de 2-3 fármacos

a dosis efectivas

Si PA no controlada

Combinación de

2-3 fármacos

Monoterapia

a dosis plena

Combinación previa

a la dosis plena

Asociar 3 fármacos

a dosis bajas

Si PA no controlada

Fármaco previo

a la dosis plena

Sustituir por otro

diferente a dosis baja

Monoterapia

a dosis bajas

Combinacion de dos

fármacos a dosis bajas

J.R.G. JUANATEY C.H.U.Santiago

Controlled BP (%)

Patients who are adherent are more likely to attain BP control

* <140/90 mmHg or <130/85 mmHg for patients with diabetes Bramley et al. J Manag Care Pharm 2006;12:239–45

45% greater probability of control

Adherence

(n = 165) (n = 46) (n = 629)

0

5

10

15

20

25

30

35

40

45

50

Low (<50%) Medium (50-79%) High (>=80%)

J.R.G. JUANATEY C.H.U.Santiago

Relative risk of a CV event

Adherence

Patients who are adherent are at lower CV risk

Mazzaglia et al. Circulation 2009;120:1598-1605

50% lower risk of a CV event

(n = 7,624) (n = 9,666) (n = 1,516)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Low (<40%) Medium (40-79%) High (>=80%)

J.R.G. JUANATEY C.H.U.Santiago

2013

CCB + TZD + ACEi (or ARB)

Stage 1 140-159/90-99

Stage 2 > 160/100

Special Cases

Start Drug Therapy (In all patients)

Black Patients non-Black Patients

Age <60

years

Age >60

years

CCB or TZD CCB or TZD ACEi or ARB

CCB or TZD

ACEi or ARB ACEi or ARB CCB or TZD ACEi or ARB

OR

Combine CCB+TZD

Strat with 2 drugs

J.R.G. JUANATEY C.H.U.Santiago

Role of Central

Aortic Pressure /

Aortic stif

ACE-I and calcium antagonist combination

ACCOMPLISH: Blood Pressure (BP) Levels During the Study

Patients, n

Benazepril/amlodipine

5,740 5,517 5,404 5,178 5,010 4,866 4,298 2,804 1,074

Benazepril/HCTZ

5,757 5,537 5,408 5,222 5,033 4,825 4,299 2,529 1,042

Benazepril/HCTZ

Benazepril/amlodipine 160

140

120

100

80

60

mm

Hg

0 3 6 12 18 14 30 36 42

Months

The mean SBP/DBP following titration was 131.6/73.3 mm Hg in the benazepril/amlodipine group and 132.5/74.4 mm Hg in the benazepril/HCTZ group. The mean

difference in SBP/DBP between the 2 groups was 0.9/1.1 mmHg (p<0.001)

1. Jamerson et al. N Engl J Med 2008;359:241728

ACCOMPLISH: Primary endpoint

0,00

0,02

0,04

0,06

0,08

0,10

0,12

0,14

0,16

0 200 400 600 800 1000 1200 1400

HR = 0.80 (95% CI 0.72–0.90)

Cu

mu

lati

ve e

ven

t ra

te

Time to 1st CV morbidity / mortality (days)

679

552

Jamerson et al. N Engl J Med 2008; 359: 2417-28

CAFÉ substudy of ASCOT: Lower central BP with amlodipine than atenolol, despite similar brachial BP

Williams et al. Circulation 2006;113:1213–25

Bra

ch

ial

Cen

tral

SB

P (

mm

Hg

)

Time (years)

Atenolol Amlodipine

Diff Mean (AUC) = 4.3 mmHg (95% CI 3.3–5.4) p<0.0001

N = 2073

115

120

125

130

135

140

0,0 0,5 1,0 1,5 2,0 2,5 3,0 3,5 4,0 4,5 5,0 5,5 6,0

RAAS Blockade Can Be Considered A

Foundation of Combination Therapy

• Targets two key mechanisms of

action

– Salt/volum (Obesity, DM, MS)

– Neurohormonal

• Additive efficacy

• Excellent BP reduction in

many demographic groups

• Potential safety/

tolerability benefits

• Targets two key mechanisms of

action:

– Pressure

– Neurohormonal

• Additive efficacy

• Excellent BP reduction in many

demographic groups

• Potential safety/

tolerability benefits

+ Diuretic* + CCB*

RAAS Blocker

RAAS=renin-angiotensin-aldosterone system

CCB=calcium channel blocker; BP=blood pressure

*Versus either drug alone

J.R.G. JUANATEY C.H.U.Santiago

Recommendation 8 In the population aged 18 years or older with CKD and hypertension,

initial (or add-on) antihypertensive treatment should include an ACEI

or ARB to improve kidney outcomes. This applies to all CKD patients

with hypertension regardless of race or diabetes status.

Moderate Recommendation – Grade B

Recommendation 7 In the general black population, including those with diabetes, initial

antihypertensive treatment should include a thiazide-type diuretic or CCB.

For general black population: Moderate Recommendation – Grade B For black

patients with diabetes: Weak Recommendation – Grade C

J.R.G. JUANATEY C.H.U.Santiago

EUA < 30 mg/g 30 – 299 mg/g > 300 mg/g

0 10 13 7

BENEDICT

ROADMAP

IRMA 2 RENAAL

IDNT DETAIL

Duración de la diabetes (años)

Normoalbuminuria Microalbuminuria Macroalbuminuria IRCT

Estudios con ARA II y con IECA en Diabetes tipo 2

Nefropatía incipiente Nefropatía establecida

MARVAL

American Diabetes Association. Diabetes Care 2008; 31 (Suppl 1): S1-S43.

Trandolapril

Olmesartan

IECA ó ARA II

Irbesartán

Valsartán

Enalapril

Telmisartán

Losartán

Irbesartán

STENO 2

Morbimortalidad cardiovascular

AVOID Aliskiren + Losartán

AMADEO Telmisartán

J.R.G. JUANATEY C.H.U.Santiago

Resistant Hypertension. Drug therapy failure

Zhang Y, et al. FEVER Study Group.

Higher CV risk and impaired benefit of antihypertensive

treatment in hypertensive patients requiring additional drugs

on top of randomized therapy: is adding drugs always

beneficial?

J Hypertens 2012; 30: 2202-2212

Weber MA, et al. FEVER Study Group.

CV outcomes in hypertensive patients: comparing single-

acting therapy with combination therapy

J Hypertens 2012; 30: 2213-2222

J.R.G. JUANATEY C.H.U.Santiago

“…from the FEVER and VALUE

studies, in patients under multidrug

treatment, CV risk was greater than

on initial monotherapy and did not

decrease as a result of a fall in BP”

“Risk irreversibility concept”

ESC / ESH 2013

J.R.G. JUANATEY C.H.U.Santiago

Resistant Hypertension. Invasive approach

Carotid baroreceptor stimulation

Renal denervation

Other invasive approaches

J.R.G. JUANATEY C.H.U.Santiago

Conclusions (my personal opinion*)

1. The BP for everyone will be < 140/90 mmHg

2. BP for those >80 y- <150/90 mmHg

3. Combinations of RAS blockers with thiazide

diuretics or RAS blockers and dihydropyridine CCBs

are good first line combos to get BP to goal, if

>20/10 mmHg above goal

J.R.G. JUANATEY C.H.U.Santiago

HTA- 2014. Nuevas Guías

Aspectos Epidemiológicos

Las Nuevas Guías y la Evaluación del Riesgo

Las Nuevas Guías y los Objetivos Terapéuticos

Las Nuevas Guías y la Selección de Fármacos

J.R.G. JUANATEY C.H.U.Santiago

J.R.G. JUANATEY C.H.U.Santiago

2013 ESH/ESC Guidelines

Selección del Fármaco

Prevención Progresión a Alto Riesgo

Regresión/Retraso Progresión LOD

Prevención Específica

IC (?)

IM (?)

Disfunción

renal

HVI

Proteinuria /

MA

Ateroesclerosis

asintomática

Deterioro

cognitivo (?)

ERT FA Nueva

DM

SM Nueva

HTA (?)

Ictus (?)

Situación Clínica

SM DM

DM ±

nefropatía

Embarazo Edad (?)

Carcaterísticas demográficas

Raza Negra IM Ictus

IC Angina

EVP

J.R.G. JUANATEY C.H.U.Santiago

2013

If Needed, Refer to a Hypertension Specialist

If Needed, add other drugs e.g. Spironolactone;

centrally acting agents, B-blockers

J.R.G. JUANATEY C.H.U.Santiago

2013 COMMENTS ON DRUG CLASSES

ACEi. Can increase serum creatinine by as much as 30%... This is a

reversible change in function and is not harmful.

ARB. These drugs do not appear to have dose-dependent side effects,

so it is perfectly reasonable to start treatment with medium or even

maximun approved doses.

TZD and TZD-like. Clinical outcome benefits with chlorthalidone,

indapamide and hydrochlorothiazide. … are most effective when

combined with ACEi or ARB

J.R.G. JUANATEY C.H.U.Santiago

2013 COMMENTS ON DRUG CLASSES

CCB. Most experience with dihydropyridines. Powerful BP reducting

effects, when combined with ACEi or ARB. They are equally effective in

all racial and ethnic groups.

B-Blockers. They have strong clinical outcome benefits in pts with

myocardial infarction, heart failure and angina pectoris. … may not be as

effective as the other drugs in preventing stroke or CV events.

Mineralcorticoid Receptor Antagonists. …, these agents can

be effective in reducting BP when added to standard 3-drug regimens in

treatment-resistant patients.

J.R.G. JUANATEY C.H.U.Santiago

Recommendation 1 In the general population aged 60 years or older, initiate pharmacologic treatment to lower BP at SBP of 150 mm Hg or higher or DBP of 90 mm Hg or higher and treat to goal SBP lower than 150 mm Hg and goal DBP lower than 90 mm Hg. Strong recommendation – Grade A

Recommendation 2 In the general population younger than 60 years initiate pharmacologic treatment to lower BP at DBP of 90 mm Hg or higher and treat to goal DBP of lower than 90 mm Hg For ages 30-59 years: Strong recommendation – Grade A For ages 18-29 years: Expert opinion – Grade E

Recommendation 3 In the general population younger than 60 years initiate pharmacologic treatment to lower BP at SBP of 140 mm Hg or higher and treat to goal SBP of lower than 140 mm Hg Expert opinion – Grade E

J.R.G. JUANATEY C.H.U.Santiago

Recommendation 4

In the population aged 18 years or older with CKD, initiate pharmacologic treatment to lower BP at SBP of 140 mm Hg or higher or DBP of 90 mm Hg or higher and treat to goal SBP of lower than 140 mm Hg and goal DBP lower tan 90 mm Hg Expert opinion – Grade E

Recommendation 5

In the population aged 18 years or older with Diabetes, initiate pharmacologic treatment to lower BP at SBP of 140 mm Hg or higher or DBP of 90 mm Hg or higher and treat to goal SBP of lower than 140 mm Hg and goal DBP lower tan 90 mm Hg Expert opinion – Grade E

Recommendation 6 In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, CCB, ACEi or ARB Moderate Recommendation – Grade B

J.R.G. JUANATEY C.H.U.Santiago

Recommendation 8 In the population aged 18 years or older with CKD and hypertension,

initial (or add-on) antihypertensive treatment should include an ACEI

or ARB to improve kidney outcomes. This applies to all CKD patients

with hypertension regardless of race or diabetes status.

Moderate Recommendation – Grade B

Recommendation 7 In the general black population, including those with diabetes, initial

antihypertensive treatment should include a thiazide-type diuretic or CCB.

For general black population: Moderate Recommendation – Grade B For black

patients with diabetes: Weak Recommendation – Grade C

J.R.G. JUANATEY C.H.U.Santiago

Recommendation 9 The main objective of hypertension treatment is to attain and maintain goal BP.

If goal BP is not reached within a month of treatment, increase the dose of the

initial drug or add a second drug from one of the classes in recommendation 6

(thiazide-type diuretic, CCB, ACEI, or ARB). The clinician should continue to

assess BP and adjust the treatment regimen until goal BP is reached. If goal BP

cannot be reached with 2 drugs, add and titrate a third drug from the list

provided. Do not use an ACEI and an ARB together in the same patient. If goal BP

cannot be reached using the drugs in recommendation 6 because of a

contraindication or the need to use more than 3 drugs to reach goal BP, anti-

hypertensive drugs from other classes can be used. Referral to a hypertension

specialist may be indicated for patients in whom goal BP cannot be attained using

the above strategy or for the management of complicated patients for whom

additional clinical consultation is needed.

Expert Opinion – Grade E

J.R.G. JUANATEY C.H.U.Santiago

Risk of coronary events in people with CKD Compared with

diabetes: a population-level Cohort study

Tonelli M, et al. Lancet 2012; 380:807-812;

Polonsky-Bakris. Lancet 2012; 380:783-785.

J.R.G. JUANATEY C.H.U.Santiago

Multiple Medication Are Required to Achieve BP

Control in Clinical Trials

Hypertension

Diabetes

Kidney

Disease

J.R.G. JUANATEY C.H.U.Santiago

Initial Combinations of Medications*

Thiazide-Like Diuretics

ACE inhibitors

or

ARBs

Calcium

antagonists

Beta-blockers should be included in the regimen if there is a compelling indication for a beta-blocker

J.R.G. JUANATEY C.H.U.Santiago

Initiation of anti-hypertensive drug treatment

J.R.G. JUANATEY C.H.U.Santiago

ESC/ESH 2013.

J.R.G. JUANATEY C.H.U.Santiago

A SBP goal < 140 mmHg

ESC/ESH 2013. Blood pressure goals in HT patients

J.R.G. JUANATEY C.H.U.Santiago

ACE-I and diuretic combination

ARB and diuretic combination

Role of Central

Aortic Pressure /

Aortic stif

J.R.G. JUANATEY C.H.U.Santiago

Role of Central

Aortic Pressure /

Aortic stif

ACE-I and calcium antagonist combination

J.R.G. JUANATEY C.H.U.Santiago

BB and diuretic combination

J.R.G. JUANATEY C.H.U.Santiago

Calcium antagonist and diuretic combination

Combination of two-RAS blockers/ACE-I+ARB or RAS blocker+renin

inhibitor

J.R.G. JUANATEY C.H.U.Santiago

ESC/ESH 2013 Guidelines.

Combinations of classes of anti-hypertensive drugs

Thiazide diuretics

Beta-blockers Angiotensin R

blockers

Calcium

antagonists

ACE inhibitors

Other

Antihypertensives

J.R.G. JUANATEY C.H.U.Santiago

Stenting and Medical Therapy for Atherosclerotic

Renal-Artery Stenosis

Stent plus medical therapy

Medical therapy alone

Hazard ratio with stenting, 0.94 (95% CI, 0.76-1.117)

P=0.58

Cooper CJ, et al. N Engl J Med 2014; 370: 13-22

did not confer a significant benefit

J.R.G. JUANATEY C.H.U.Santiago

World’s biggest killers – CVD

retain top spot

J.R.G. JUANATEY C.H.U.Santiago

Medication CV predictive value Availability Reproducibility Cost-effect

ESC/ESH 2013.

Guidelines Markers of organ damage

J.R.G. JUANATEY C.H.U.Santiago

Globalisation of CV Disease

J.R.G. JUANATEY C.H.U.Santiago

BRIC countries are closing the gap

on the US and Europe

J.R.G. JUANATEY C.H.U.Santiago

Adherence rates to common CV medications

Aspirin

Lipid-lowering agents

Beta blockers

Aspirin + beta blockers

Aspirin + beta blockers +

lipid lowering agents

83

63

61

54

39

71

46

44

36

21

Medication Self-reported

adherence %

consistent adherence

%

Not following the script

J.R.G. JUANATEY C.H.U.Santiago

Finnish CVD – legacy of the North Karelia project

Strat of the North Karelia project

Extension of the project nationally

J.R.G. JUANATEY C.H.U.Santiago

ESC/ESH: Definitions of Hypertension by

Office and Out-of-Office BP levels

J.R.G. JUANATEY C.H.U.Santiago

Convetional, 24-h, Daytime, and Nightime SBP

as Predictor of CV End-Points: Syst-Eur

J.R.G. JUANATEY C.H.U.Santiago

Changes in Office BP After Renal

Denervation

J.R.G. JUANATEY C.H.U.Santiago

Changes in ABPM After Renal Denervation

J.R.G. JUANATEY C.H.U.Santiago

Obesidad

Alcoholismo

Tabaquismo

Dislipemia

Diabetes

HTA-no C

HTA-R

HTA-C

%

62%

43%

8%

59%

11%

55%

68%

6%

3%

5% p<0,05

38%

61%

9%

6%

54%

p<0,001

p = ns

p<0,05

p<0,001

Sínd Metab p<0,001

68%

22%

52%

Estudio HIPERFRE Peor Control de PA en Pacientes de Mayor Riesgo

Otero-Raviña F, González-Juanatey JR et al. Nefrología 2008

J.R.G. JUANATEY C.H.U.Santiago

1 2 3 0 4

Edad

Sexo (H)

Diabetes

Obesidad

Sínd Metab

Card Isq

1,03 <0,01

1,62 <0,05

6,34 <0,001

1,51 <0,05

4,36 <0,001

0,40 <0,01

OR p

5 6 7 8

Estudio HIPERFRE

Factores asociados a HTA refractaria

Otero-Raviña F, González-Juanatey JR et al. Nefrología 2008

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