Advances in Heart Failure Jonathan D Davis, MD, MPHS Director, - - PowerPoint PPT Presentation

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Advances in Heart Failure Jonathan D Davis, MD, MPHS Director, - - PowerPoint PPT Presentation

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Advances in Heart Failure Jonathan D Davis, MD, MPHS Director, Heart Failure Program Assistant Clinical Professor | Division of Cardiology Zuckerberg San Francisco General Hospital Department of Medicine | University of California, San

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Zuckerberg San Francisco General

Advances in Heart Failure

Jonathan D Davis, MD, MPHS

Director, Heart Failure Program Assistant Clinical Professor | Division of Cardiology Zuckerberg San Francisco General Hospital Department of Medicine | University of California, San Francisco jonathan.davis@ucsf.edu | @JonathanDavisHF June 15, 2020

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Zuckerberg San Francisco General

Disclosures

  • I have no relevant financial relationships with any

companies related to the content of this course.

Advances in Heart Failure 2

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Overview

  • Heart Failure Survival and Outcomes
  • Heart Failure with Preserved EF (HFpEF, EF >50%)
  • Heart Failure with Reduced EF (HFrEF, EF <40%)
  • Medical Therapies
  • Devices
  • Key Take Home: New Standard of Care for HFrEF

Advances in Heart Failure 3

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Heart Failure Epidemiology

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Advances in Heart Failure 5

Park JJ, et al. JACC. 2018;71(18):1947-57) Vasan RS, et al. JACC Cardiovasc Imaging. 2017

Poor Survival Regardless of EF

HFrEF HFmrEF HFpEF

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Advances in Heart Failure 6

Mortality Increases with Each Hospitalization

Setoguchi S et al. Am Heart J. 2007;154:260-266. Loehr LR, et al. Am J Cardiol. 2008;010:1016-1022

  • 30-day all-cause mortality after 1st admission: 10-12%
  • 1-year all-cause mortality after 1st admission: 22-34%
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Zuckerberg San Francisco General

Heart Failure with Preserved Ejection Fraction

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Medications with a Class I Recommendation for HFpEF

Advances in Heart Failure 8

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  • Primary outcome: 13% relative risk reduction (RR, 0.87;

95% CI, 0.75 - 1.01; P = 0.06)

  • For sacubitril/valsartan as compared to valsartan:
  • No difference in death from cardiovascular causes (HR 0.95;

95% CI, 0.79 to 1.16)

  • Suggestion of reduction in total HF hospitalizations (rate

ratio, 0.85; 95% CI, 0.72 to 1.00)

  • NYHA Class Improved (odds ratio, 1.45; 95% CI, 1.13 to 1.86)

Advances in Heart Failure 9

Solomon, SD, et al. NEJM. 9/1/19.

PARAGON-HF October 24, 2019

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Zuckerberg San Francisco General

Pooling Sacubitril/Valsartan Data

  • Pre-specified pooled analysis of 13,195 patients from

PARADIGM-HF (EF ≤40%) & PARAGON-HF (EF ≥45%)

  • Overall, sacubitril/valsartan was superior for:
  • 1st CV death or HF hospitalization (HR 0.84, 95% CI 0.78, 0.90)
  • Cardiovascular death (HR 0.84, 95% CI 0.76, 0.92)
  • Heart failure hospitalization (HR 0.84, 95% CI 0.77, 0.91)
  • All-cause mortality (HR 0.88, 95% CI 0.81, 0.96)

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Solomon, SD, et al. Circulation. 11/17/19.

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Continuous Treatment Effects of ARNI

  • vs. Active Comparator by Sex

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Solomon SS, et al. Circulation. 2020;141:352–361

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Advances in Heart Failure 12

  • 15,682 fee‐for‐service

Medicare patients. 1857 were treated w/ rhythm control & 13,825 w/ rate control

  • Lower 1‐year all‐cause death

in rhythm control group (after risk adjustment; adjusted HR, 0.86; 95% CI, 0.75–0.98; P=0.02)

Kelly JP, et al. JAHA. Vol 8, Issue 24. 17 Dec 2019

Rhythm Control Versus Rate Control in Patients With Atrial Fibrillation and HFpEF

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Heart Failure with Reduced Ejection Fraction

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Guideline-Directed Medical Therapy

  • Current State, Class I Recommendations:
  • RAAS inhibition (Class I)
  • Beta blocker (Class I)
  • Mineralocorticoid Receptor Antagonist (Class I)
  • Hydralazine/isosorbide dinitrate (Class I)
  • BUT: Utilization is Suboptimal

Advances in Heart Failure 14

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New GDMT: Quad Therapy

  • Angiotensin receptor neprilysin inhibitor (ARNI)
  • Beta blocker
  • Mineralocorticoid (aldosterone) antagonist
  • SGLT2-Inhibitor
  • Hydralazine/isosorbide dinitrate
  • New: Vericiguat and Omecamtiv Mecarbil

Advances in Heart Failure 15

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Suboptimal GDMT Use – CHAMP

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Greene SJ, et al. JACC. 2018 Jul, 72 (4) 351-366.

33% 26% 66%

ONLY 22.1% were simultaneously prescribed some dose

  • f ACEI/ARB/ARNI, beta-blocker, and MRA therapy
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Angiotensin receptor neprilysin inhibitor

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Sacubitril/Valsartan – PARADIGM-HF

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McMurray JJV, et al. NEJM 2014; 371:993-1004

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Advances in Heart Failure 19

A: Primary outcome of all-cause mortality or hospitalization B: All-cause mortality

Tan NY, et al. JACC HF. 2020;8(1)43-54

Comparative Effectiveness of ARNI v ACE/ARB

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Transitioning to Sacubitril/Valsartan

  • NYHA II-III, BNP > 150 pg/mL or > 100 pg/mL if HF

admission in last 12 months

  • 36-hour washout from ACE but not ARB
  • Lisinopril ≤ 10 mg/day  24/26 mg BID
  • Sacubitril has natriuretic effects
  • If hypotensive, orthostatic, new AKI  decrease diuretic

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SGLT2-Inhibitor

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  • 7020 patients for median observation time of 3.1 years
  • Primary composite outcome: death from cardiovascular

causes, nonfatal myocardial infarction, or nonfatal stroke

  • Inclusion:
  • eGFR ≥ 30 ml per minute per 1.73 m2 of body-surface area
  • A1c 7-10% if had received stable glucose-lowering therapy

for at least 12 weeks before randomization

Diabetes Medications and Heart Failure 22

EMPA-REG OUTCOME. N Engl J Med 2015;373:2117-28.

EMPA-REG OUTCOME November 26, 2015

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Diabetes Medications and Heart Failure 23

EMPA-REG OUTCOME. N Engl J Med 2015;373:2117-28.

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EMPA-REG OUTCOME. N Engl J Med 2015;373:2117-28.

Glycemic Control

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Diabetes Medications and Heart Failure 25

Kluger AY et al. Cardiovasc Diabetol (2019) 18:99

HHF HHF HHF HHF MACE MACE MACE MACE HHF or CV death HHF or CV death HHF or CV death HHF or CV death HHF: Hospitalization for HF MACE: Major adverse cardiovascular events

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DAPA-HF Trial

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  • Dapagliflozin 10 mg vs. placebo, 4744 patients
  • New York Heart Association class II, III, or IV
  • Ejection fraction of 40% or less
  • 60% of enrolled WITHOUT Diabetes
  • Primary outcome was a composite of worsening HF

(hospitalization or an urgent visit resulting in IV therapy for HF) or CV death

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Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. NEJM. 9/19/19.

DAPA-HF September 19, 2019

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Diabetes Medications and Heart Failure 28

DAPA-HF. NEJM. 9/19/19.

Characteristic Dapagliflozin (N = 2373) Placebo (N = 2371) Age – years 66.2 ± 11.0 66.5 ± 10.8 Female – No. (%) 564 (23.8) 545 (23.0) Race – No. (%) White 1662 (70) 1671 (70.5) Black 122 (5.1) 104 (4.4) Asian 552 (23.3) 564 (23.8) NYHA Class – No. (%) II 1606 (67.7) 1597 (67.4) III 747 (31.5) 751 (31.7) IV 20 (0.8) 23 (1.0) Principal Cause of HF – No. (%) Ischemic 1316 (55.5) 1358 (57.3) Nonischemic 857 (36.1) 830 (35.0)

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Diabetes Medications and Heart Failure 29

DAPA-HF. NEJM. 9/19/19.

Characteristic Dapagliflozin (N = 2373) Placebo (N = 2371) HF Medication – No. (%) ACE Inhibitor 1332 (56.1) 1329 (56.1) ARB 675 (28.4) 632 (26.7) Sacubitril-valsartan 250 (10.5) 258 (10.9) Beta-blocker 2278 (96.0) 2280 (96.2) MRA 1696 (71.5) 1674 (70.6) Device Therapy – No. (%) ICD 622 (26.2) 620 (26.1) CRT 190 (8.0) 164 (6.9)

~96%

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DAPA-HF. NEJM. 9/19/19.

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Similar Outcomes Regardless of Diabetes Status

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DAPA-HF. NEJM. 9/19/19. Petrie MC, et al. JAMA. 2020;323(14):1353-1368

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Variable Dapagliflozin Placebo P Value (N=2373) (N=2371) DAPA-HF. NEJM. 9/19/19.

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Advances in Heart Failure 33

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Vaduganathan M, et al. Lancet. 2020 May 21;S0140-6736(20)30748-0

Comprehensive therapy: ARNI, β blocker, MRA, and SGLT2 inhibitor Conventional therapy: ACE inhibitor or ARB and β blocker

Quad Therapy: The New Standard in the Treatment of HFrEF

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New Medications for HFrEF

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Advances in Heart Failure 36

Armstrong PW, et al. JACC HF. 2018

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Advances in Heart Failure 37

Armstrong PW, et al. N Engl J Med 2020; 382:1883-1893

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Omecamtiv Mecarbil (OM)

Advances in Heart Failure 38

Teerlink JR, et al. JACC HF. 2020 Apr, 8 (4) 329-340.

Myosin Head Actin Filament

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GALACTIC-HF Trial

  • Hypotheses: OM can safely improve symptoms, prevent

clinical HF events, and delay CV death in patients with chronic HF

  • > 8,000 patients with chronic symptomatic (NYHA II to IV)

HF, LVEF ≤35%, elevated natriuretic peptides, and either current hospitalization for HF or history of hospitalization

  • r emergency department visit for HF within a year of

screening

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Teerlink JR, et al. JACC HF. 2020 Apr, 8 (4) 329-340.

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HFrEF: Devices

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Device Therapy

  • ICD
  • CRT
  • MitraClip
  • Invasive Monitoring
  • CardioMEMS – Reduce risk of HF readmission
  • Cordella – In clinical trial

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Zeitler EP, et al. JACC HF. 2020;8(4):251-64)

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Take Home Points

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Diabetes Medications and Heart Failure 44

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GDMT WORKS!

  • Some is better than none, more is better than less
  • Switch to Sacubitril/Valsartan
  • Don’t forget spironolactone
  • Start an SGLT2-Inhibitor
  • If EF recovers, DO NOT STOP the HF medications
  • Titration of medical therapy is hard, so go slow, be

patient and don’t give up!

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Thank you!

jonathan.davis@ucsf.edu @JonathanDavisHF