Objetivo de tensión arterial en 2016. Importancia de la adherencia terapéutica y recomendaciones para la elección del tratamiento 20/01/2016 20:00h Casa del Corazón (Madrid) http://hta16.secardiologia.es #HTA16 ¿Objetivos iguales para todos los pacientes? ¿Qué pasa con los pacientes con enfermedad coronaria? Dr. José Ramón González-Juanatey, C.H.U.S. (Santiago de Compostela). Presidente anterior SEC @JoseJuanatey

1. J.R.G. JUANATEY
C.H.U.Santiago
Objetivos de Presión Arterial en Pacientes con
Cardiopatía Isquémica
“No nos dejemos llevar por la primera impresión”
José R. González Juanatey
Hospital Clínico Universitario de Santiago de Compostela

2. J.R.G. JUANATEY
C.H.U.Santiago
Objetivos de PA en pacientes con cardiopatía
isquémica
•Recomendaciones de las Guías de práctica clínica
•La “curva J”
•¿Cambian los nuevos estudios las recomendaciones?
•Y en práctica clínica, ¿qué hacemos?

3. 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
Relativerisk
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 BPUKPDS 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
DIABHYCARCAPPP-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

4. J.R.G. JUANATEY
C.H.U.Santiago
Objetivos del Tratamiento:
Reducción de PA y Riesgo CVC Global
Riesgo absoluto añadido de enfermedad CVC a 10 años :
Normal
PAS 120-129
o
PAD 80-84
Normal Alta
PAS 130-139
o
PAD 85-89
Complicaciones
CVC Clínicas
3 o mas FRC, o
Diabetes o LOD
1 o 2 Fact. Riesgo
Adicionales
No otros Factores
Riesgo
Grado 3
PAS 180
o
PAD 110
Grado 2
PAS 160-179
o
PAD 100-109
Grado 1
PAS 140-159
o
PAD 90-99
< 15% 15-20% 20-30% > 30%Framingham
< 4% 4 – 5% 5-8% > 8%SCORE
BP 178/106

5. Recent updates to blood pressure goals reflect limited
evidence of benefit <140/90 mmHg
*<130/80 mmHg in chronic kidney disease and albuminuria; †SBP < 130 mmHg in nephropathy.
1. Rydén et al. Eur Heart J 2013;34:3035–87. 2. Mancia et al. J Hypertens 2013;31:1281–357.. 3. http://guidance.nice.org.uk/CG127;
4. http://www.nice.org.uk/guidance/cg87; 5. Weber. J Hypertens 2014;32:3–15; 6. James. JAMA 2014;5;311:507–20.
7. American Diabetes Association. Diabetes Care 2015;38(suppl. 1):S1–S94. 8. Daskalopoulou et al. Can J Cardiol 2015;31:549–68.
Guidelines Goal BP (mmHg)
General Diabetes Elderly (≥80 years)
ESC/EASD 20131 <140/85†
ESH/ESC 20132 <140/90 <140/85 <150/90
NICE 20113,4 <140/90 <140/80* <150/90
ASH/ISH 20135 <140/90 <140/90* <150/90
JNC 8 20146 <140/90 <140/90*
<150/90
(Aged ≥60 years)
ADA 20157 <140/90
CHEP8 <140/90 <130/80 <150/90

6. 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…”

7. 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
140 y 150
140 y 150
Pacientes con cardiopatía isquémica

8. 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

9. J.R.G. JUANATEY
C.H.U.Santiago
Objetivos de PA en pacientes con cardiopatía
isquémica
•Recomendaciones de las Guías de práctica clínica
•La “curva J”
•¿Cambian los nuevos estudios las recomendaciones?
•Y en práctica clínica, ¿qué hacemos?

10. J.R.G. JUANATEY
C.H.U.Santiago
What is the optimal blood pressure after
Acute Coronary Syndomes? PROVE IT TIMI 22
Non-fatal Myocardial Infarction
Nadir = 134.2 mmHg Nadir = 83.8 mmHg
SBP mmHg DBP mmHg
Circulation 2010; 122: 2142-2151

11. 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)
% %

12. J.R.G. JUANATEY
C.H.U.Santiago
Incidence and Unadjusted CV Risk of Events
in Deciles of In-treatment SBP
Unadjustedriskofevents(%)
HR(95%CI)
On-treatment SBP (mmHg) Unadjustedriskofevents(%)
HR(95%CI)
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)

13. Reference
Tight BP control and CV outcomes among HT patients with Diabetes
and Coronary Artery Disease. INVEST
All-cause Mortality
JAMA 2010; 304: 61-68

14. CV outcomes from the ACCOMPLISH trial
OUTCOMES: (MI, stroke, revascularization, all-cause mortality)
Weber M, et al. Am J Med 2013

15. J.R.G. JUANATEY
C.H.U.Santiago
¿Curva “J” o Relación Lineal entre PA e IAM?
100%
50%
0%
Riesgo
Presión Arterial

16. J.R.G. JUANATEY
C.H.U.Santiago
lower diastolic pressure
higher LV end-diastolic pressure
reduced
coronary
perfusion in
diastole
cardiovascular disease
healthy

17. J.R.G. JUANATEY
C.H.U.Santiago
The “J curve” between Blood Pressure
and Coronary Artery Disease
Patients with revascularization
Patients without revascularization
DBP (mmHg)
HazardRatio
JACC 2009; 54: 1827-1834

18. J.R.G. JUANATEY
C.H.U.Santiago
Objetivos de PA en pacientes con cardiopatía
isquémica
•Recomendaciones de las Guías de práctica clínica
•La “curva J”
•¿Cambian los nuevos estudios las recomendaciones?
•Y en práctica clínica, ¿qué hacemos?

19. J.R.G. JUANATEY
C.H.U.Santiago
Pre-specified Subgroups of Special Interest
• Age (<75 vs. ≥75 years)
• Gender (Men vs. Women)
• Race/ethnicity (African-American vs. Non African-
American)
• CKD (eGFR <60 vs. ≥60 mL/min/1.73m2)
• CVD (CVD vs. no prior CVD)
• Level of BP (Baseline SBP tertiles: ≤132, 133 to 144,
≥145 mm Hg)-

20. Systolic BP During Follow-up
Mean SBP
136.2 mm Hg
Mean SBP
121.4 mm Hg
Average SBP
(During Follow-up)
Standard:
134.6 mm Hg
Intensive:
121.5 mm Hg
Average number of
antihypertensive
medications
Number of
participants
Standard
Intensive
Year 1

21. Number of
Participants
Hazard Ratio = 0.75 (95% CI: 0.64 to 0.89)
Standard
Intensive
(243 events)
During Trial (median follow-up = 3.26 years)
Number Needed to Treat (NNT)
to prevent a primary outcome = 61
SPRINT Primary Outcome
Cumulative Hazard
(319 events)

22. SPRINT Primary Outcome and its Components
Event Rates and Hazard Ratios
Intensive Standard
No. of
Events
Rate,
%/year
No. of
Events
Rate,
%/year
HR (95% CI) P value
Primary Outcome 243 1.65 319 2.19 0.75 (0.64, 0.89) <0.001
All MI 97 0.65 116 0.78 0.83 (0.64, 1.09) 0.19
Non-MI ACS 40 0.27 40 0.27 1.00 (0.64, 1.55) 0.99
All Stroke 62 0.41 70 0.47 0.89 (0.63, 1.25) 0.50
All HF 62 0.41 100 0.67 0.62 (0.45, 0.84) 0.002
CVD Death 37 0.25 65 0.43 0.57 (0.38, 0.85) 0.005
-28?

23. Include NNT
All-cause Mortality
Cumulative Hazard
Hazard Ratio = 0.73 (95% CI: 0.60 to 0.90)
During Trial (median follow-up = 3.26 years)
Number Needed to Treat (NNT)
to Prevent a death = 90
Standard
(210 deaths)
Intensive
(155 deaths)
Number of
Participants

24. SPRINT Primary Outcome
Subgroup analysis

25. Intensive Standard
Events %/yr Events %/yr HR (95% CI) P
Participants with
CKD at Baseline
Primary CKD outcome 14 0.33 15 0.36 0.89 (0.42, 1.87) 0.76
≥50% reduction in
eGFR*
10 0.23 11 0.26 0.87 (0.36, 2.07) 0.75
Dialysis 6 0.14 10 0.24 0.57 (0.19, 1.54) 0.27
Kidney transplant 0 - 0 - - .
Secondary CKD Outcome
Incident albuminuria** 49 3.02 59 3.90 0.72 (0.48, 1.07) 0.11
Participants
without CKD at
Baseline
Secondary CKD outcomes
≥30% reduction in eGFR* 127 1.21 37 0.35 3.48 (2.44, 5.10) <.0001
Incident albuminuria** 110 2.00 135 2.41 0.81 (0.63, 1.04) 0.10
Renal Disease Outcomes
*Confirmed on a second occasion ≥90 days apart **Doubling of urinary albumin/creatinine ratio from <10 to >10 mg/g

26. Risk of coronary events in people with myocardial
infarction compared with diabetes: a population-level
Cohort study
Tonelli M, et al. Lancet 2012; 380:807-812;
Polonsky-Bakris. Lancet 2012; 380:783-785.

27. ACCORD BP trial: SBP and Outcomes

28. Effects of a 10
mmHg
reduction in SBP
stratified by BP
Ettehad D, et al., Lancet 2015;
on line december

29. Reduction in major CV events regressed against the
difference in achieved SBP
Ettehad D, et al., Lancet 2015; on line december

30. Even small reductions in BP can reduce risk in
high CV risk patients
Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2014;384:591–8.
Small BP reductions in
high-risk individuals
avoid as many events as
large BP reductions in
low-risk individuals
CVevents
avoidedper1000

31. Effect of 10 mmHg reduction in SBP on CV outcomes by
baseline ≥ 140 or < 140 mmHg
Meta-analysis of 40 trials of BP-lowering treatment including patients with diabetes (n=100,354 participants).
Emdin et al. JAMA 2015;313:603–15.
0.5 1.0 2.0
Favours BP lowering Favours control
Overall
Baseline SBP <140 mmHg
Baseline SBP 140 mmHg
Outcome
Mortality
CVD
CHD
Stroke
Relative risk (95% CI)

32. CV outcomes based on mean SBP achieved (≥ 130
or < 130 mmHg
Meta-analysis of 40 trials of BP-lowering treatment including patients with diabetes (n=100,354 participants).
Emdin et al. JAMA 2015;313:603–15.
0.5 1.0 2.0
Favours BP lowering Favours control
Overall
Achieved SBP <130 mmHg
Achieved SBP 130 mmHg
Outcome
Mortality
CVD
CHD
Stroke
Relative risk (95% CI)

33. J.R.G. JUANATEY
C.H.U.Santiago
Objetivos de PA en pacientes con cardiopatía
isquémica
•Recomendaciones de las Guías de práctica clínica
•La “curva J”
•¿Cambian los nuevos estudios las recomendaciones?
•Y en práctica clínica, ¿qué hacemos?

34. J.R.G. JUANATEY
C.H.U.Santiago
The Cochrane Hypertension Review group at the
University of British Columbia in Vancouver has
looked closely at the “lower the better” issue. They
were able to take the results of this trial, add it to the
10 trials of lower vs standard blood pressure targets,
to conclude the big picture does not change.
Despite SPRINT, the systematic evidence, which
should be considered much more reliable, says that
patients given the most intensive regimen to lower
their BP down to say 120 over 80 do not do any better
than those who are given standard therapy.

35. J.R.G. JUANATEY
C.H.U.Santiago
Should we target an SBP < 120 mmHg?
In FAVOUR of an SBP target < 120 mmHg
1) The potential benefits are clinically meaningful
This trial showed a statistically benefit in the primary,
a composite of CV events and all-cause mortality in patients
using the more intensive SBP regimen.
primary CV composite: NNT=63/3.3 yrs
all-cause mortality: NNT=83/3.3 yrs
2) The CV and mortality benefit may make it worth
trouble shooting tolerability and adverse event risks for some
patients.

36. J.R.G. JUANATEY
C.H.U.Santiago
Should we target an SBP < 120 mmHg?
AGAINST an SBP target < 120 mmHg
1) There are potential harms which must be weighed against the
potential benefits, including:
. Serious adverse events related to intervention NNH=45/3.3 yrs
.syncope NNH=83/3.3 yrs
.hypotension NNH=100/3.3 yrs
.electrolyte abnom. NNH=200/3.3 yrs
.acute renal failure NNH=63/3.3 yrs
.more CKD progrs. NNH=37/3.3yrs
2) This trial has design issues which may bias results or limit our
ability to apply it findings.
Open-label nature of the trial
Stopping trial early (limits evaluation of long term safety) (benefit vs harm)
Exclusion of institutionalized adults, those with stroke, diabetes or
recent CV disease symptoms, low CV risk.

37. J.R.G. JUANATEY
C.H.U.Santiago
SPRINT Uncertanties
. To what extent are the results generalizable to
patients who did not meet the inclusion/exclusion
criteria? (high and low-risk)
Of US adults only about 17% of HT patients meet the SPRINT criteria
. Is lower better in all patients?
The J-curve in a high CV risk population may be significant
. What is the impact on cognition?
Results remain unreported
. Will patients in the real-world be able to achieve
the needed adherence to the intensive medication
regimen?

38. J.R.G. JUANATEY
C.H.U.Santiago
SPRINT Uncertanties
. There are real-world drawbacks to pursuing
agressive targets
More medications (mean 2.8 vs 1.8). More monitoring, cost, risk of
polypharmacy, SAE and drug interactions.
. One needs to consider results from previous trials
JATOS and VALISH did not find benefit in reducing SBP below 140
mmHg in patients with BP 140-150 or 160 mmHg. COCHRANE review
did not find benefit in reducing SBP below 140 mmHg.
ACCORD-BP trial showed no difference in 1º outcome CV events for
T2DM patients assigned to SBP<120 mmHg vs 140 mmHg.
Previous data has found reducing DBP below 60 mmHg may increase
risk in patients with CV disease (J-curve effect)

39. J.R.G. JUANATEY
C.H.U.Santiago
Objetivos de PA en pacientes con cardiopatía
isquémica
•En Cardiología, ¡Que peligro tiene la “fascinación” por los
resultados del último ensayo clínico!
•En pacientes con cardiopatía isquémica no existe una sólida
evidencia para modificar los actuales objetivos de presión arterial.
•Individualización de los objetivos en función de características
clínicas, presencia de comorbilidades, empleo de fármacos y
estrategias de reconocido benecio pronóstico.