hospitalization

Cambios en la Enfermedad Cardiovascular
en el último año
Implicaciones para la Práctica Clínica
Insuficiencia Cardíaca
Prof. Domingo A. Pascual Figal
Hospital Universitario Virgen de la Arrixaca
Facultad de Medicina, Murcia
2011 Top Game Changers in Cardiology:
………………………………
and the Top Game Changer Is...
Objetivo primario
(Mortalidad CV u hospitalización por IC)
Mortalidad CV u hospitalización por IC (%)
100
HR = 0,63
60
(IC 95% 0,54-0,74)
p < 0,001
50
Placebo
40
30
Eplerenona
20
10
0
0
Nº de pacientes en riesgo
Placebo
Eplerenona
1.373
1.364
1
2
3
Años desde la aleatorización
848
925
512
562
199
232
Conclusiones
• En los pacientes con IC con disfunción sistólica
y síntomas leves, la adición de eplerenona al
tratamiento médico optimo:
– fue bien tolerada
– mejoró la supervivencia
– y previno hospitalizaciones
En el corto y
En el largo plazo
• NNT
– Objetivo primario, por año de seguimiento, es 19
– Para aplazar una muerte, por año de seguimiento, es 51
Click here for PI
Disposition of Patients
2737 Randomized
1364 Randomized
to eplerenone
No AFF
N= 911 (66.8%)
1373 Randomized
to placebo
AFF
N= 453 (33.2%)
No AFF
N= 883 (64.3%)
No AFF
N= 1794 (65.5%)
AFF
N= 943 (34.5%)
Median follow-up time 21 months,
AFF
N= 490 (35.7%)
Click here for PI
New Onset Atrial Fibrillation/Flutter (AFF)
New Onset AFF
Cumulative Rate
(%)
10
HR [95% CI] = 0.58 [0.35, 0.96]
P = 0.034
8
Placebo
6
Eplerenone
4
2
0
0
1
2
3
4
Years from Randomization
No. at Risk
Placebo
Eplerenone
883
911
611
627
345
397
133
162
1
2
Click here for PI
Effects of eplerenone by baseline AFF:
without AFF
Total number of
subjects
Eplerenon
e
n = 911 (%)
Placebo
n = 883
(%)
Hazard
Ratio
P-value
160 (17.6%) 217 (24.6%)
0.70
<0.001
175 (19.2%) 228 (25.8%)
0.72
0.001
260 (28.5%) 294 (33.3%)
0.83
0.03
Without AFF
CV death/HF
Hospitalization
All-cause mortality or
HF hospitalization
All-cause
hospitalization
HF hospitalization
103 (11.3%)
150 (17.0%)
0.65
<0.001
All cause death or all
292 (32.1%) 341 (38.6%)
0.81
<0.01
156 (17.7%)
0.65
<0.001
201 (22.1%) 244 (27.6%)
0.77
<0.01
cause hospitalization
HF death or HF
107 (11.7%)
hospitalization
CV hospitalization
Click here for PI
Effects of eplerenone by baseline AFF:
with AFF
Placebo
N = 490
N (%)
Hazard
Ratio
P-value
P-value for
interaction
with/withou
t AFF
89 (19.6%)
139 (28.4%)
0.60
<0.001
0.41
95 (21.%)
148 (30.2%)
0.60
<0.001
0.28
148 (32.7%)
197 (40.2%)
0.70
<0.01
0.22
HF hospitalization
61 (13.5%)
103 (21.0%)
0.56
<0.001
0.49
All cause death or all
170 (37.5%)
228 (46.5%)
0.70
<0.001
0.26
63 (13.9%)
106 (21.6%)
0.56
<0.001
0.49
Total number of
subjects
Eplerenon
e
N = 453
N (%)
With AFF
CV death/HF
Hospitalization
All-cause mortality or
HF hospitalization
All-cause
hospitalization
cause hospitalization
HF death or HF
hospitalization
Click here for PI
CV death or HF hospitalization by
baseline atrial fibrillation/flutter (AFF)
CV Death / HF
Hospitalization
Cumulative Rate (%)
HR [95% CI] = 1.13 [0.96, 1.33]
P = 0.153
40
With Baseline AFF
30
20
Without Baseline AFF
10
0
0
1
2
3
4
Years from Randomization
No. at Risk
With AFF
Without AFF
943
1794
602
1171
385
689
161
270
2
4
Click here for PI
Study outcomes by baseline AFF
AFF
No AFF
P-value
(N=943)
(N=1 794)
N (%)
N (%)
HF Hospitalization/CV Death
HF Hospitalization
228 (24.2%)
377 (21.0%)
0.153
164 (17.4%)
253 (14.1%)
0.059
CV Death
All-cause mortality or heart
failure (HF) hospitalization
All-cause mortality
All-cause hospitalization
All cause death or all cause
hospitalization
HF death or HF hospitalization
CV hospitalization
122 (12.9%)
210 (11.7%)
0.643
243 (25.8%)
403 (22.5%)
0.153
139 (14.7%)
245 (13.7%)
0.789
345 (36.6%)
554 (30.9%)
0.019
398 (42.2%)
633 (35.3%)
0.008
169 (17.9%)
263 (14.7%)
0.067
258 (27.4%)
445 (24.8%)
0.355
¡HIPOTENSIÓN¡
HeartWare
HeartMate II
DOT-HF trial
SMART-AV
Study Design
Patient with Class II-IV symptoms, EF  40%, recent HF event
Randomization echocardiogram
Standard of Care
Standard of Care + NT-proBNP
Minnesota Living With HF
Questionnaire quarterly
Minnesota Living With HF
Questionnaire quarterly
Therapy adjusted to achieve
optimal drug targets
Therapy adjusted to achieve optimal drug
targets PLUS NT-proBNP  1000 pg/mL
Visits q3 months
Visits q3 months
Extra visits as needed for treatment goals
Extra visits as needed for treatment goals
Close-out echocardiogram
Total cardiovascular events assessed
NT-proBNP Concentrations
Overall
Baseline
Follow-up
P
2118 [1122-3831] 1321 [554-3197] .02
By treatment allocation
Treatment
Baseline
Follow-up
P
SOC
1946 [951-3488] 1844 [583-3603] .61
NT-proBNP 2344 [1193-4381] 1125 [369-2537] .01
P = .03 for SOC follow-up versus NT-proBNP follow-up
44.3% of NT-proBNP subjects 1000 pg/mL
Primary Endpoint
P =.009
120
100 events
Number of events
100
80
60
40
20
58 events
*Logistic OddsNT-proBNP= 0.44
(95% CI= .22-.84; P =.019)
0
Total CV Events
*Adjusted for age, LVEF, NYHA Class, and eGFR
SOC
NT-proBNP
Individual Endpoints
60
NB: 0 cerebral ischemia events in either arm
SOC
NT-proBNP
Number of events
50
40
NB: 3 of 4 CV deaths in NT-proBNP arm
occurred after elective withdrawal from study
30
20
10
P =.001
P =.002
P =.72
P =.41
P =.52
Worsening
HF
HF hosp
ACS
VT/VF
CV death
0
Age and outcomes
Mean number of events
1,8
1,6
SOC
NT-proBNP
1,4
1,2
1
0,8
0,6
0,4
P =.008
P =.005
Age < 75 years
Age ≥ 75 years
0,2
0
*No interaction between age and NT-proBNP guided care was found (P =.11)
Safety
SOC
NT-proBNP
P =.08
P =.47
Acute
renal failure
Dizziness
Hypo or
hyperkalemia
Hypotension
Syncope
H
/h
y
yp
o
H
yn
co
S
te
n
rk
a
pe
yp
o
ss
in
e
iz
z
D
fa
al
A
cu
t
e
re
n
Adverse events
pe
P =.32
si
on
P =.70
le
m
ia
P =.72
ilu
re
% with events
8
7
6
5
4
3
2
1
0
Minnesota Living with Heart
Failure Questionnaire
NT-proBNP patients had larger QOL improvements
than SOC, and were more likely to have large
(≥10 point) improvements in their MLWHF scores
Variable
SOC
NT-proBNP
P
Global Scale -5.0 [-18-0] -10.0 [IQR -17-7] .05
38.8%
61.2%
.03
≥10 point 
Selected echo results
20
SOC (N= 56)
NT-proBNP (N=60)
15
% change
10
P =.06
P =.01
LV end-systolic LV end-diastolic
volume index
volume index
5
0
-5
-10
-15
-20
LVEF
Absolute 
LVEF
Relative 
P <.001
P =.008
sST2
Acute HF: Other Tools are Inadequate…
ST2 Most Predictive of Mortality
 ST2 predicted mortality
better than other
demographic variables
and biomarkers
 ST2 provides valuable
information not
available from existing
tools
 Hypertension, CAD,
Diabetes, Ejection Fraction,
and Smoking were not
significant predictors of
mortality, but were
evaluated.
Hazard Ratio
4
3,5
3
2,5
2
1,5
1
0,5
0
ST2 > 35
ng/mL
NT-proBNP
> median
BNP >
median
Prior
Congestive
HF
NYHA
Severity
(per
functional
class)
Age (per
year)
*HR shown if p<.05; univariate HRs are given. ST2 HR is forST2>35 ng/mL from
PRIDE dataset; additional data provided by investigators to Critical Diagnostics.
For ST2 > median, HR is 2.85.
Rehman S, et al.. Characteristics of the Novel Interleukin Family Biomarker ST2 in Patients with Acute Heart Failure. J. Am. Coll. Cardiol. 2008;52(18):1458-1465.
Januzzi JL Jr, et al. Importance of Biomarkers for Long-term Mortality Prediction in Acutely Dyspneic Patients. Clin Chem. 2010 Dec; 56(12):1814-21. Epub 2010 Oct 4.
72
ST2 in Acute Heart Failure
ST2 values associated with:
– More symptomatic HF
– Lower EF
– Higher NP levels
Not affected by age, sex, BMI, etiology of HF, AF,
anemia (unlike NP’s)1
Strong association between ST2 levels at presentation
and 1-year mortality
– Cut-point of 30 ng/ml
1Shah
et al. Circ Heart Fail 2009
73
ST2 Give an Earlier Signal For
Short Term Adverse Events than NPs
Acute (Pooled Acute)
Isn’t an Earlier Signal By Definition A More Clinically Useful Signal?
74
ST2 Relationship to Time of All Cause Mortality
in Stable, Ambulatory HF Patients
75
Cumulative Adverse Event Rates ST2 Value >35 ng/ml
for Death, Transplant or Cardiovascular Hospitalization
76
ST2 Predicts Response to Aldosterone
Blockade
 ST2 predicts which patients will
benefit most from aldosterone
blockade.
 Eplerenone attenuates remodeling
more in patients with a higher
baseline ST2
 ST2 not only predicts outcomes but
also predict which patients will
benefit most from intervention.
High and low ST2 separated at median.
Weir AP, et al. J. Am. Coll. Cardiol. 2010;55;243-250.
77
Implicaciones
• Incuestionable beneficio del bloqueo de la
aldosterona en pacientes con disfunción
sistólica.
• La reducción de la FC con ivabradina reduce
síntomas (estabilidad) y el remodelado
ventricular.
• El uso inicial de dosis altas de diuréticos en
bolos ev es seguro y puede mejorar la
evolución en pacientes con IC aguda
Implicaciones
• En pacientes con IC y FE preservada la
mejora sintomática debe ser el objetivo, sin
olvidar un enfoque periférico
• El beneficio de la resincronización queda
claro incluso en estadíos poco sintomáticos
o asintomáticos.
• La monitorización con dispositivos de
presión o de impedancia queda relegada,
mientras que la expansión de la asistencia
ventricular es imparable.