medical management of heart failure in the clinic

Medical Management of Heart Failure in the Clinic

Henry Tran, MD, MSc, FACP

April 12, 2017

Learning Goals Utilize latest definitions and terminology to more

accurately described patients with heart failure (HF) To be able to initiate and manage optimal medical

therapy for HF Understand major side effects and adverse events

associated with the major classes of medications for HF Recognize indications for the use of newest medical

therapies: Sacubitril/Valsartan (Entresto®) Ivabradine (Corlanor®)

Guidelines 2013 ACCF/AHA Guideline for the

Management of Heart Failure 2016 ACC/AHA/HFSA Focused Update on

New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure

Clinical Case

Mr. Jackson is a 74 year old man with diabetes and hypertension who complains of dyspnea and lower extremity edema for the past month. He hasn’t seen a physician in one year. He remembers being told last year his ejection fraction was 45%.

He recently ran out of metformin 500mg twice a day, lisinopril 10mg, and atenolol 50mg daily.

On exam he has jugular venous distension, bilateral crackles, S3 heart sound, and 2+ pitting edema.

How would you change this patient’s management?

Definitions

Heart Failure (HF)HFpEF HFrEF

Heart Failure Definitions(HF) HF is a complex clinical syndrome that results from any

structural or functional impairment of ventricular filling or ejection of blood which is notable for: dyspnea and fatigue Fluid retention, which may lead to pulmonary and/or

splanchnic congestion and/or peripheral edema.

“Heart Failure” is preferred over “congestive heart failure (CHF)” some patients have little evidence of fluid retention and

present without signs or symptoms of volume overload

Yancy, CW et al. ACCF/AHA Heart Failure Guideline

Question 1 Mr. Jackson is a 74 year old man with

diabetes and hypertension who complains of dyspnea and lower extremity edema for the past month. He hasn’t seen a physician in one year. He remembers being told last year his ejection fraction was 45%.

Is this heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF)?

Definitions of HFrEF & HFpEFClassification EF

(%)Heart Failure with reduced Ejection Fraction (HFrEF)

≤40 aka systolic HF

Heart Failure with preserved Ejection Fraction (HFpEF)

≥50 Diastolic HF

a) HFpEF, borderline 41-49 Treatment patterns and outcomes similar to HFpEF

b) HFpEF, improved >40 Who previously had HFrEF


2015 ASE Guidelines for Chamber Quantification

Male FemaleSevere Mod Mild Normal Severe Mod Mild Normal

LVEF <30 30-40 41-51 52-72 <30 30-40 41-53 53-74

HFpEF HFpEF

HFrEF HFrEF

HFpEF, borderlin

e

HFpEF, borderli

ne

HF Classifications

Question 2 Mr. Nguyen has Stage C HFrEF (LVEF 30%), NYHA

III. He hasn’t been compliant with medications or follow-up in many years. He presents with dyspnea and fatigue.

He needs to be re-initiated on treatment for HF. Besides metoprolol succinate (Toprol) and

carvedilol, nebivolol treatment is evidence-based and guideline supported. True or False.

Beta Blocker: Not a class effect

Starting Max Mean Dose in Trials

Bisoprolol 1.25mg daily 10mg daily 8.6 mg/d

Carvedilol 3.125mg twice 50mg twice 37 mg/d

Carvedilol CR 10mg once 80mg once N/A

Metoprolol Succinate

12.5 to 25 mg once

200mg daily 159 mg/d


Beta Blocker: Goals

Initiate at low dose with progressive uptitration

Goal is to maximize highest dose possible Carvedilol 25mg BID or Toprol XL 200 mg

Titration limited gby excessive bradycardia, hypotension, or orthostatic intolerance

85% of patients in trials were able to take max doses

Question 3

For Mr. Nguyen, eventually the initiation of either Lisinopril or Losartan is preferred over other ACE inhibitors or ARBs.

True or False

ACE inhibitor or ARB


Q: ACE Inhibitor and ARB for HFrEF Mr. Trump is 69 yo man with ICM, LVEF 40%, NYHA III. He recently was

hospitalized for orthopnea and huge LE edema. Huge weight gain. In the office, he continues to complain of severe dyspnea after 3

blocks. Current meds: Lisinopril 40mg daily, Coreg 25mg BID, aspirin 81mg,

atorvastatin 80mg Allergies: Spironolactone and eplerenone BP 110/78 HR 64 Should losartan be added to his treatment? Or substituted for

lisinopril 40?

CLASS IIb

1. Addition of an ARB may be considered in persistently

symptomatic patients with HFrEF who are already being treated

with an ACE inhibitor and a beta blocker in whom an aldosterone

antagonist is not indicated or toleratedYancy, CW et al. ACCF/AHA Heart Failure Guideline

Aldosterone Antagonists

Mr. Sanders is a 74 yo male with ischemic cardiomyopathy, NYHA III. Most recent LVEF is 35%. He uses coreg 25mg BID, lisinopril 40mg daily, and lasix 40mg daily.

His most recent creatinine is 2.3 mg/dL (estimated GFR 32 ml/min/1.73 m2). K is 4.8.

Is he a suitable candidate be initiated on either spironolactone or eplerenone?

RALESThe risk of death was 30 percent lower among patients in the spironolactone group than among patients in the placebo group (P<0.001).

RALES Investigators. NEJM 1999

Aldosterone Antagonists Aldosterone receptor antagonists to reduce morbidity and mortality in

patients with: NYHA class II–IV HF LVEF of 35% or less Patients with NYHA class II HF should have a history of prior cardiovascular

hospitalization or elevated plasma natriuretic peptide levels to be considered for aldosterone receptor antagonists.

Creatinine should be < 2.5 mg/d in men < 2.0 mg/dL in women GFR >30 ml/min/1.73 m2

potassium should be less than 5.0 mEq/L.

Aldosterone receptor antagonists are recommended to reduce morbidity and mortality following an acute MI in patients who have LVEF of 40% or less who develop symptoms of HF or who have a history of diabetes mellitus,

Loop DiureticsDrug Maximum Daily

DoseDuration

Furosemide 600 mg 6-8 hrsBumetanide 10mg 4-6 hrsTorsemide 200mg 12-16 hrs

• Adjust doses based on weights• Monitor for potassium and magnesium depletion


Hydralazine and Nitrates

African-american patients with symptomatic HFrEF despite beta blocker, ACE inhibitors, and aldosterone inhibitors

Poor adherence due to frequency of dosing: TID

GDMT RR Reduction

in Mortality

NNT (standardize for 36

mo)

RR Reduction

in HF hosp

ACE Inhibitoror ARB

17 26 31

Beta Blocker

34 9 41

Aldosterone Antagonist

30 6 35

Hydralazine/nitrate

43 7 33


HFpEF: Therapies Most therapeutic trials have been negative Target blood pressure control

Use general BP targets

Diuretic usage (spironolactone) to treat volume overload Probably benefit based on subgroup analysis of TOPCAT

trial

ARB might be beneficial to reduce HF hospitalization (Class IIB)

New Pharmacologic Therapies

LCZ696

co-crystallized valsartan and sacubitril, in a one-to-one molar ratio

Sacubitril/Valsartan (Entresto)

PARADIGM HF

• 8442 patients with HFrEF, LVEF ≤ 40%, NYHA II-IV• LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a

dose of 10 mg twice daily), in addition to recommended therapy.

• Trial stopped early due to excessive benefit of Entresto• 20% Relative Risk reduction in primary endpoint• 16% Relative risk reduction in all-cause mortality

McMurray JJ, et al. NEJM 2014

2016 Guidelines

In patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality (Class IB)

Resting HR Predicts Outcomes

Benes J el al. JCHF 2013

Ivradabine

Very selective for If 2005 approved in Europe 2015 FDA

Ivradabine

Reduced hospitalizations but no mortality benefit!

2016 Guidelines

Ivabradine can be beneficial to reduce HF hospitalization for patients with symptomatic (NYHA class II-III) stable chronic HFrEF (LVEF ≤35%) who are receiving GDEM, including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at res.

Conclusions

HFrEF (LVEF ≤40%) and HFpEF (LVEF >40%) define spectrum of heart failure

Optimal medical therapy for HFrEF involves beta blockers, ACE inhibitor/ARB, and aldosterone African-American: hydralazine/nitrates

Progressive titration of OMT to achieve maximum doses Sacubitril/valsartan should be considered for all patients

with continued symptomatic HFrEF

Thank You

Can metoprolol tartate be used instead of metoprolol succinate in HFrEF?

• 3029 patients with LVEF <35%, NYHA II-IV

• Randomized to carvedilol (target dose 25 mg twice daily) or metoprolol tartate (target dose 50 mg twice daily)

• The primary endpoints were all-cause mortality and the composite endpoint of all-cause mortality or all-cause admission.

ARR 6%P<0.017NNT 16.6

ICD +/- CRT NYHA II-IV: ICD therapy recommended at least 40 days

Post-MI with LVEF ≤ 35% NYHA I: ICD recommended at least 40 days post-MI

with LVEF ≤ 30% CRT is indicated for patients who have LVEF of 35% or

less, sinus rhythm, left bundle-branch block (LBBB) with a QRS >150 ms

Should be considered only in the setting of optimal GDMT and with a minimum of 3 to 6 months of appropriate medical therapy.

medical management of heart failure in the clinic

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