Novedades en el manejo de la
Insuficiencia Cardiaca con FEVI
Preservada
Manuel Méndez
Servicio de Medicina Interna
Hospital Clínico San Carlos
1. Oktay, Rich, Shah Curr Heart Fail Rep 2013. 2. Bello NA et al. Circ Heart Fail. 2014;7:590-595
IC: insuficiencia cardiaca; FEp: fracción de eyección preservada; FE: fracción de eyección
Las Hospitalizaciones en ICFEp están en aumento
La ICFEp un síndrome clínico heterogéneo
( cardíaco /comorbilidades)
1. Oktay, Rich, Shah Curr Heart Fail Rep 2013. 2. Bello NA et al. Circ Heart Fail. 2014;7:590-595
IC: insuficiencia cardiaca; FEp: fracción de eyección preservada; FE: fracción de eyección
European Heart Journal, ehz641, https://doi.org/10.1093/eurheartj/ehz641
The content of this slide may be subject to copyright: please see the slide notes for details.
European Heart Journal, ehz641, https://doi.org/10.1093/eurheartj/ehz641
The content of this slide may be subject to copyright: please see the slide notes for details.
ESC HFA PEFF Score
Perfiles fenotípicos y terapéuticos en IC
TRATAMIENTO DE LA IC-Fep SEGÚN LAS GUÍAS
Ponikowski P et al. Eur Heart J 2016
Yancy et al. Circulation. 2017
Manejo de la congestión basado en ecografía clínica ( ICFEp). Ensayo EPICC
Los ensayos clínicos de morbimortalidad en ICFEp que no han demostrado
eficacia
CHARM-Preserved PEP-CHF
Perindopril
I-PRESERVE TOPCAT
Pro
po
rtio
n
ha
vin
ga
ne
ve
nt
(%)
Pro
po
rtio
n
ha
vin
ga
ne
ve
nt
(%)
Cu
mu
lati
ve
incid
en
ce
of
pri
ma
ry
eve
nts
(%)
Pro
ba
bil
ity
30
25
20
15
10
5
0
30
15
10
5
0
50
40
30
20
10
0
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00
320/177 (18.6%)
351/1723 (20.4%)
Placebo
Spironolactone
HR 0.89 (95%CI 0.77–1.01),
p=0.138
36 48 60 72
Months
HR 0.92 (95% CI0.70–1.21),
p=0.545
100 (23.6%)
107 (25.5%)
Placebo
Months
0 1 2 3 3.5 0 1 2 3
Years Years
0 6 12 18 24 30 36 42 48 54 60 0 12 24
Placebo
Placebo
Candesartan
Irbesartan
HR 0.95 (95% CI 0.86–1.05)
Log-rankp=0.35
HR 0.89 (95% CI 0.77–1.03), p=0.118
Adjusted HR0.86, p=0.051
366 (24.3%)
333 (22.0%)
N=4,128
Mean f ollow-up: 49.5 months
Af ib, atrial f ibrillation; CAD, coronary artery disease; CI, conf idence interv al; HFpEF, heart f ailure with preserv ed ejection f raction; HR, hazard ratio; HTN, hy pertension; M&M, mortality and morbidity ;
PEP-CHF, The perindopril in elderly people with chronic heart f ailure; TOPCAT, Treatment of Preserv ed Cardiac Function Heart Fai lure with an Aldosterone Antagonist
ENSAYOS CLÍNICOS EN IC-FEp
PARAGON-HF
Study design
~2 weeks Valsartan 160 mg BID
Sac/val
100 mg BID
On top of optimal background medications for
comorbidities (excluding ACEIs and ARBs)
Valsartan 80 mg BID
Screening
Single-blind run-in
period
Sacubitril/valsartan 200 mg BID
Double-blind, long-term follow-up
period¥Randomization
N = 4822
1─4
weeks*
2─4
weeks^
Safetyand
tolerability
check
Safety and
tolerability
check
A randomized, double-blind, parallel group, active-controlled, event driven trial
*Eligible patients were exposed to valsartan 80 mg BID for 1─2 weeks. Patients on low pre-study ACEI/ARB doses or those with tolerability concerns were first started on valsartan 40 mg BID 1─2 weeks and
then up-titrated to valsartan 80 mg BID for 1─2 weeks
^Patients tolerating valsartan 80 mg BID for 1─2 weeks were switched to sacubitril/valsartan 100 mg BID for 2─4 weeks
¥Follow-up visits occurred at 4, 16, 32, and 48 weeks and every 12 weeks thereafter. All patients were followed until target number of primary composite(CV deaths and total HF hospitalizations) occur or 26
months after randomization of the last patient elapse, whichever occurs last
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BID, twice daily; CV, cardiovascular; HF, heart failure
Solomon SD et al. JACC Heart Fail.2017;5:471-482
919
09
0690
01
PARAGON-HF
Key eligibility criteria
11
Solomon S, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction: primary results of the PARAGON-HF trial. Oral presentation at ESC 2019,
Paris, France
Solomon S, et al. N Engl J Med. 2019
Key inclusion criteria
• ≥ 50 years of age and LVEF ≥ 45%
• Heart failure signs/symptoms (NYHA Class II-IV) requiring
treatment with diuretic(s) for at least 30 days prior to
enrollment
• Structural heart disease (LAE or LVH by
echocardiography)
• Elevation in natriuretic peptides
- NT-proBNP 200 pg/mL if hospitalized for HF within 9 months,
and 300 pg/mL if not hospitalized; 3-fold increase for patients in
AF at enrollment
Key exclusion criteria
• Any prior measurement of LVEF < 40%
• Current acute decompensated heart failure
• Alternative reason for signs and symptoms
• SBP < 110 or ≥ 180 mmHg (or > 150 mmHg if patient not taking 3 or more
antihypertensive medications)
HF, heart failure; LAE, left atrial enlargement; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; NT-proBNP, N-terminal pro-B- type natriuretic
peptide; NYHA, New York Heart Association; SBP, systolic blood pressure
19
09
0690
01
1
4
Primary endpoint ─ Recurrent event analysis of total
HF hospitalizations and CV death*
*Semiparametric LWYY method.
CV, cardiovascular; HF, heart failure
Solomon S, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction: primary results of the PARAGON-HF trial. Oral presentation at ESC 2019, Paris, France.
19
09
0690
01
Significant Heterogeneity in Multivariate Analysis by
Ejection Fraction and Sex
15
CI, confidence intervals; LVEF, left ventricular ejection fraction
Solomon S, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction: primary results of the PARAGON-HF trial. Oral presentation at ESC 2019, Paris,France.
¿La ICFEp es un síndrome clínico diferente entre hombres y
mujeres?
PARAGON:Secondary endpoints
Solomon S, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction: primary results of the PARAGON-HF trial. Oral presentation at ESC 2019, Paris,
France.
Sacubitril/valsartan (n = 2316)
Valsartan (n = 2302)
Effect size (95% CI) Nominal p-value
NYHA functional classification at
8 months
Odds ratio for improvement0.004
1.45 (1.13, 1.86)Improved 15.0% 12.6%
Unchanged 76.3% 77.9%
Worsened 8.7% 9.6%
KCCQ clinical summary score at 8 months*
─ Change from baseline (SE) -1.6 (0.4) -2.6 (0.4)LSM of difference
1.03 (0.00 to 2.1) 0.051
KCCQ responder (>5 point improvement) 33.0% 29.6%Odds ratio
0.0191.30 (1.04 to 1.61)
Worsening renal function† 1.4% 2.7%Hazard ratio
0.50 (0.33 to 0.77)0.002
All-cause mortality 14.2% 14.6%Hazard ratio
0.680.97 (0.84 to 1.13)
1719
09
0690
01
Significant Heterogeneity in Multivariate Analysis by
Ejection Fraction and Sex
18
CI, confidence intervals; LVEF, left ventricular ejection fraction
Solomon S, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction: primary results of the PARAGON-HF trial. Oral presentation at ESC 2019, Paris,France.
¿Es útil la definición de IC FE intermedia?
¿Una molécula o varias pueden controlar la IC FEp?
¿La ICFEp es una enfermedad que necesita de un tratamiento
individualizado?