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?