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