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