2016 Update to Heart Failure Clinical Practice Guidelineswcm/@hcm/@gwtg/documents… · 2016 Update...
Transcript of 2016 Update to Heart Failure Clinical Practice Guidelineswcm/@hcm/@gwtg/documents… · 2016 Update...
2016 Update to Heart FailureClinical Practice Guidelines
Tuesday August 2, 2016 1:00pm – 2:00pm CST (60 minute webinar)
Presenters: Dr. Gregg Fonarow, MD, FACC, FAHA, FHFSA Dr. Clyde Yancy, MD, MSc, MACC, FAHA, MACP Dr. Paul Heidenreich, MD, MS, FACC
8/2/2016 ©2013, American Heart Association 2
Gregg C. Fonarow, MD, FACC, FAHAThe Eliot Corday Professor of Cardiovascular Medicine and ScienceCo-Chief of Clinical Cardiology UCLA Division of CardiologyDirector, Ahmanson-UCLA Cardiomyopathy CenterCo-Director, UCLA Preventative Cardiology Program
Clyde W. Yancy, MD, MSc, MACC, FAHA, MACPVice Dean, Diversity & InclusionMagerstadt Professor of MedicineProfessor of Medical Social SciencesChief, Division of CardiologyNorthwestern University, Feinberg School of MedicineAssociate Director, Bluhm Cardiovascular Institute
Paul A Heidenreich, MD, MS, FACC
Associate Professor of MedicineVice-Chair for Clinical, Quality and Analytics,
Department of MedicineStanford University
2016 Update to Heart Failure Clinical Practice Guidelines
• New Epidemiology
• New Therapies
• New Guidelines
• New Phenotype
Date of download: 6/10/2016
Copyright © 2016 American Medical Association. All rights reserved.
From: A Contemporary Appraisal of the Heart Failure Epidemic in Olmsted County, Minnesota, 2000 to 2010
JAMA Intern Med. 2015;175(6):996-1004. doi:10.1001/jamainternmed.2015.0924
Temporal Trends in Heart Failure Incidence Rates Overall and by Reduced or Preserved Ejection Fraction Among Women and Men in Olmsted County, Minnesota, 2000 to 2010Yearly rates (smoothed using 3-year moving average) per 100 000 persons have been standardized by the direct method to the age distribution of the US population in 2010. HFpEF indicates heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction.
Figure Legend:
A Contemporary Appraisal of the HF Epidemic• Age and sex-specific incidence of heart failure has declined
– 315/100,000 to 219/100,000
• Rate reduction of 37.5%
• Incidence decline was greater for HFrEF – 45.1% vs. HFpEF -27.9%
• Risk for CV death was lower for HFpEF but the same for non-CV death
• Hospitalizations have increased 34%
• Most hospitalizations, 63%, were due to non-cardiovascular causes
• Thus today’s epidemic of heart failure is defined by a marked increase in
hospitalizations, predominance of non-CV death rate, and persistence and
predominance of HFpEF Roger VL et al. JAMA Intern Med. 2015; April 20. Epub ahead of print.
Stages, Phenotypes and Treatment of HFSTAGE A
At high risk for HF but without structural heart
disease or symptoms of HF
STAGE BStructural heart disease
but without signs or symptoms of HF
THERAPYGoals• Control symptoms• Improve HRQOL• Prevent hospitalization• Prevent mortality
Strategies• Identification of comorbidities
Treatment• Diuresis to relieve symptoms
of congestion• Follow guideline driven
indications for comorbidities, e.g., HTN, AF, CAD, DM
• Revascularization or valvular surgery as appropriate
STAGE CStructural heart disease
with prior or current symptoms of HF
THERAPYGoals• Control symptoms• Patient education• Prevent hospitalization• Prevent mortality
Drugs for routine use• Diuretics for fluid retention• ACEI or ARB• Beta blockers• Aldosterone antagonists
Drugs for use in selected patients• Hydralazine/isosorbide dinitrate• ACEI and ARB• Digoxin
In selected patients• CRT• ICD• Revascularization or valvular
surgery as appropriate
STAGE DRefractory HF
THERAPYGoals• Prevent HF symptoms• Prevent further cardiac
remodeling
Drugs• ACEI or ARB as
appropriate • Beta blockers as
appropriate
In selected patients• ICD• Revascularization or
valvular surgery as appropriate
e.g., Patients with:• Known structural heart disease and• HF signs and symptoms
HFpEF HFrEF
THERAPYGoals• Heart healthy lifestyle• Prevent vascular,
coronary disease• Prevent LV structural
abnormalities
Drugs• ACEI or ARB in
appropriate patients for vascular disease or DM
• Statins as appropriate
THERAPYGoals• Control symptoms• Improve HRQOL• Reduce hospital
readmissions• Establish patient’s end-
of-life goals
Options• Advanced care
measures• Heart transplant• Chronic inotropes• Temporary or permanent
MCS• Experimental surgery or
drugs• Palliative care and
hospice• ICD deactivation
Refractory symptoms of HF at rest, despite GDMT
At Risk for Heart Failure Heart Failure
e.g., Patients with:• Marked HF symptoms at
rest • Recurrent hospitalizations
despite GDMT
e.g., Patients with:• Previous MI• LV remodeling including
LVH and low EF• Asymptomatic valvular
disease
e.g., Patients with:• HTN• Atherosclerotic disease• DM• Obesity• Metabolic syndrome orPatients• Using cardiotoxins• With family history of
cardiomyopathy
Development of symptoms of HFStructural heart
disease
Yancy, C. Jessup M, Bozkurt B. et al. JACC 2013
HFrEF Stage CNYHA Class I – IV
Treatment:
For NYHA class II-IV patients. Provided estimated creatinine
>30 mL/min and K+ <5.0 mEq/dL
For persistently symptomatic African Americans, NYHA class III-IV
Class I, LOE AACEI or ARB AND
Beta Blocker
Class I, LOE CLoop Diuretics
Class I, LOE AHydral-Nitrates
Class I, LOE AAldosterone Antagonist
AddAdd Add
For all volume overload, NYHA class II-IV patients
Pharmacologic Treatment for Stage C HFrEF
Yancy, C et al. JACC 2013
Residual Risk for HFrEF Despite Conventional GDMT
In PARADIGM-HF, study patients were followed over a median of 27 months.2,*
*Adult patients with NYHA class II–IV symptoms and an ejection fraction of 40% or less were required to take a stable dose of a beta blocker and an ACE inhibitor (or ARB) equivalent to at least 10 mg of enalapril daily, with most also receiving MRA.
McMurray J et al. N Engl J Med. 2014;371:993-1004.
Of all patients randomized to enalapril, the absolute risk of CV death as a first event was 10.9% (n=459/4212)1
Endogenousvasoactive peptides
(natriuretic peptides, adrenomedullin,bradykinin, substance P,
calcitonin gene-related peptide)
Inactive metabolites
Neurohormonal activation
Vascular tone
Cardiac fibrosis, hypertrophy
Sodium retention
Neprilysin Neprilysininhibition
McMurray JJV, et al. N Engl J Med. 2014;371:993-1004.
Effects of Neprilysin Inhibition in Heart Failure
Sac/Val = Sacubitril/Valsartan. McMurray JJV, et al. N Engl J Med. 2014;371:993-1004.
Number needed to treat = 21
PARADIGM-HF: Primary Endpoint of CV Death or Heart Failure Hospitalization
Number at RiskSac/ValEnalapril
0 180 540 900Days since Randomization
00.10.2
0.4
0.6
1.0
Enalapril1117 events (26.5%)
Sac/Val914 events (21.8%)
1260
Cum
ulat
ive
Pro
babi
lity
41874212
36633579
22572123
15441488
896853
360 720 1080
0.3
0.5
39223883
30182922
249236
HR 0.80 (95% CI, 0.73–0.87), p<0.001
Sac/Val(n=4187)
Enalapril(n=4212)
Hazard Ratio(95% CI)
p-Value
Primary endpoint
914(21.8%)
1117(26.5%)
0.80(0.73–0.87) <0.001
Cardiovascular death
558(13.3%)
693(16.5%)
0.80(0.71–0.89) <0.001
Hospitalization for heart failure
537(12.8%)
658(15.6%)
0.79(0.71–0.89) <0.001
Sac/Val = Sacubitril/Valsartan.
McMurray JJV, et al. N Engl J Med. 2014;371:993-1004.
PARADIGM-HF: Effect of Sac/Val vs. Enalapril on the Primary Endpoint and Its Components
McMurray JJV, et al. N Engl J Med. 2014;371:993-1004.
Sac/Val vs. Enalapril on Primary Endpoint and on CV Death by Subgroups
All PatientsAge
<65 years≥65 years
SexMaleFemale
NYHA ClassI or IIIII or IV
Estimated GFR<60 mL/min/1.73 m2
≥60 mL/min/1.73 m2
Ejection fraction≤35%>35%
NT-proBNP≤Median>Median
HypertensionNoYes
Prior use of ACE inhibitorNoYes
Prior use of aldosterone antagonistNoYes
Prior hospitalization for heart failureNoYes
Death from Cardiovascular Causes
1.70.3
Sac/Val Better
Primary EndpointHazard Ratio
(95% CI)p-Value forInteraction
Hazard Ratio(95% CI)
p-Value forInteractionNo.
Sac/Val Enalapril
1.51.31.10.90.70.5
Enalapril Better
1.70.3
Sac/Val Better
1.51.31.10.90.70.5
Enalapril Better
4212
21682044
3259953
31301076
15202692
3722489
21162087
12412971
9463266
18122400
15452667
4187
21112076
3308879
31871002
15412646
3715472
20792103
12182969
9213266
19162271
15802607
0.47
0.63
0.03
0.91
0.36
0.16
0.87
0.09
0.10
0.10
0.70
0.92
0.76
0.73
0.36
0.33
0.14
0.06
0.32
0.19
Subgroup
Sac/Val(n=4187)
Enalapril(n=4212)
p-Value
Prospectively identified adverse eventsSymptomatic hypotension 14.0% 9.2% <0.001
Serum potassium > 6.0 mmol/L 4.3% 5.6% 0.007
Serum creatinine ≥ 2.5 mg/dL 3.3% 4.5% 0.007
Cough 11.3% 14.3% <0.001
Discontinuation for adverse event 10.7% 12.3% 0.03Discontinuation for hypotension 0.9% 0.7% 0.38
Discontinuation for hyperkalemia 0.3% 0.4% 0.56
Discontinuation for renal impairment 0.7% 1.4% 0.002
Angioedema (adjudicated)Medications, no hospitalization 6 (0.1%) 4 (0.1%) 0.52
Hospitalized; no airway compromise 3 (0.1%) 1 (<0.1%) 0.31
Airway compromise 0 0 —
McMurray JJV, et al. N Engl J Med. 2014;371:993-1004.
PARADIGM-HF: Adverse Events
New FDA-Approved Sacubitril/Valsartan
Sacubitril/Valsartan
Brand name Entresto
IndicationThe fixed-dose combination of the neprilysin inhibitor sacubitril and the ARB valsartan is indicated to reduce the risk of CV death and HF hospitalization in patients with HF with reduced ejection fraction.
Dosage Start with 49/51 mg twice daily. Double the dose after 2–4 weeks as tolerated to maintenance dose of 97/103 mg twice daily.
Renal/hepatic impairment
For patients not currently taking an ACEI or ARB, or for those with severe renal impairment (eGFR <30 mL/min/1.73 m2) or moderate hepatic impairment, start with 24/26 mg twice daily.
Switching from an ACE inhibitor Stop ACE inhibitor for 36 hours before starting treatment.
ContraindicationsHistory of angioedema related to previous ACE inhibitor or ARB, concomitant use of ACE inhibitors, concomitant use of aliskiren in patients with diabetes. WARNING – pregnancy, hyperkalemia.
Side effects Hypotension, hyperkalemia, cough, dizziness, renal failure, and angioedema (0.5% Sac/Val vs. 0.2% Enalapril).
http://www.pdr.net/full-prescribing-information/entresto?druglabelid=3756. Accessed October 20, 2015.
Practical Points on Use of Sacubitril/Valsartan
• Starting dose is 24/26 mg twice daily, unless patient is currently tolerating full
dose ACEI or ARB in which case start 49/51 mg twice daily
• Target dose is 97/103 mg twice daily
• After 2-4 weeks uptitrate to next dose with ultimate goal to achieve target dose
• Monitor SBP, renal function and K as you would with ACEI or ARB use
• Space out dosing from other vasoactive medications if needed
• Adjust diuretics doses based on volume status
Ivabradine
• Acts by inhibiting the If channel,
present in the cardiac SA node
• Reduces persistently elevated heart
rate
• Evaluated as treatment of HFrEF who
have a resting HR of at least 70 beats
per minute, in sinus rhythm, and who
are also taking the highest tolerable
dose of a beta blockerDiFrancesco D. Curr Med Res Opin. 2005;21:1115-1122.
SA node
SHIFT Study: Primary Endpoint of CV Death or Hospitalization for Worsening HF
Swedberg K, et al. Lancet. 2010;376:875-885.
0 12 18 24 30
40
10
0
Months
20
30
6
Ivabradine (n=3241)
Placebo (n=3264)P
atie
nts
with
Prim
ary
End
poin
t (%
)−18%
Placebo937 events (29%)
Ivabradine793 events (24%)
HR 0.82 (95% CI, 0.75–0.90) p<0.0001
ARR = 5%, NNT = 20
SHIFT Study: Effect of Ivabradine on Outcomes
Endpoint Ivabradine(n=3241)
Placebo(n=3264) HR p-Value
Primary endpoint 24% 29% 0.82 <0.0001
All-cause mortality 16% 17% 0.90 0.092
Death from HF 3% 5% 0.74 0.014
All-cause hospitalization 38% 42% 0.89 0.003
Any CV hospitalization 30% 34% 0.85 0.0002
CV death, hospitalization for worsening HF, or hospitalization for non-fatal MI
25% 30% 0.82 <0.0001
Swedberg K, et al. Lancet. 2010;376:875-885.
New FDA-Approved IvabradineIvabradine
Brand name Corlanor
Indication
To reduce the risk of hospitalization for worsening HF in patients with stable, symptomatic chronic HF with LVEF ≤ 35% who are in sinus rhythm with resting HR ≥70 bpm and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use.
Dosage
Start with 5 mg twice daily. After 2 weeks of treatment, adjust dose based on HR. Max is 7.5 mg twice daily. In patients with conduction defects or in whom bradycardia could lead to hemodynamic compromise, start with 2.5 mg twice daily.
Contraindications
Acute decompensated HF; BP <90/50 mmHg; sick sinus syndrome or third-degree AV block, unless a functioning demand pacemaker is present; resting HR <60 bpm prior to treatment; severe hepatic impairment; pacemaker dependence. WARNING – fetal toxicity.
Side effects Occurring in ≥1% of patients are bradycardia, hypertension, atrial fibrillation, and luminous phenomena (phosphenes).
http://www.pdr.net/full-prescribing-information/corlanor?druglabelid=3713. Accessed October 20, 2015.
Practical Points on Use of Ivabradine
• Starting dose is 5 mg twice daily
• Target HR is 50-60 bpm
• After 2 weeks:
– If HR >60 bpm:
Increase dose to 7.5 mg twice daily (Max dose)
– If HR 50-60 bpm:
Maintain initial dose
– If HR <50 bpm or symptomatic bradycardia:
Lower dose to 2.5 mg twice daily
– If HR <50 bpm or symptomatic bradycardia and dose is 2.5 mg twice daily: Discontinue
Pharmacologic Treatment for Stage C HFrEF
HFrEF Stage CNYHA Class I – IV
Treatment:
For NYHA class II-IV patients. Provided estimated creatinine
>30 mL/min and K+ <5.0 mEq/dL
For persistently symptomatic African Americans, NYHA class III-IV
Class I, LOE AACEI or ARB AND
Beta Blocker
Class I, LOE CLoop Diuretics
Class I, LOE AHydral-Nitrates
Class I, LOE AAldosterone Antagonist
AddAdd Add
For all volume overload, NYHA class II-IV patients
? Valsartan/Sacubutril? Ivabradine
Strategies:Disease ManagementRemote PA monitoringProcess ImprovementPatient EducationFrailty AssessmentPalliative CareGenetic Counseling
New Guidelines Have Emerged- 2016
COR/LOE 2016
RAASi in Heart Failure and Post-MI LV Dysfunction
Post-MILow EF
Mild-Mod CHFLow EF
CHFSevere HF
CHFPreserved EF
ACEi1 AIRESAVE
SOLVD CONSENSUS PEP-CHF(perindopril)
MRA EPHESUS1
(eplerenone)EMPHASIS1
(eplerenone)RALES1
(spironolactone)TOPCAT2
(spironolactone)
ARB1 OPTIMAALVALIANT
ELITE-IIHEALL
VAL-HeFTCHARM
CHARM-Preserved
I-PRESERVE
ARNI3 PARADIGM-HF(LCZ-696)
1. Mentz RJ, et al. Int J Cardiol. 2013:167:1677-1687. 2. Pitt B, et al. N Engl J Med. 2014;370(15):1383-1392. 3. McMurray JJV, et al. N Engl J Med 2014;371:993-1004.
RAASi=renin-angiotensin-aldosterone inhibitor; MI=myocardial infarction; EF: ejection fraction; CHF=chronic heart failure; ACEi=angiotensin-converting enzyme inhibitor; MRA=mineralocorticoid receptor antagonist; ARB=angiotensin II receptor blocker; ARNI=angiotensin receptor-neprilysin inhibitor.
RAAS inhibition- 2016
ACE-I & ARB- 2016
ARNI 2016
ARNI – (Harm) 2016
Ivabradine 2016
ESC HF Guidelines 2016
ESC HFrEF Treatment Algorithm
A new classification?
ESC HF GUIDELINES 2016
Definition of Heart Failure- ACC/AHA 2013Classification Ejection
FractionDescription
I. Heart Failure with Reduced Ejection Fraction (HFrEF)
≤40% Also referred to as systolic HF. Randomized clinical trials have mainly enrolled patients with HFrEF and it is only in these patients that efficacious therapies have been demonstrated to date.
II. Heart Failure with Preserved Ejection Fraction (HFpEF)
≥50% Also referred to as diastolic HF. Several different criteria have been used to further define HFpEF. The diagnosis of HFpEF is challenging because it is largely one of excluding other potential noncardiac causes of symptoms suggestive of HF. To date, efficacious therapies have not been identified.
a. HFpEF, Borderline 41% to 49% These patients fall into a borderline or intermediate group. Their characteristics, treatment patterns, and outcomes appear similar to those of patient with HFpEF.
b. HFpEF, Improved >40% It has been recognized that a subset of patients with HFpEF previously had HFrEF. These patients with improvement or recovery in EF may be clinically distinct from those with persistently preserved or reduced EF. Further research is needed to better characterize these patients.
Yancy C et al, JACC 2013
Date of download: 7/11/2016
Copyright © 2016 American Medical Association. All rights reserved.
From: Characteristics and Outcomes of Adult Outpatients With Heart Failure and Improved or Recovered Ejection Fraction
JAMA Cardiol. Published online July 06, 2016. doi:10.1001/jamacardio.2016.1325
Kaplan-Meier Curves, Adjusted for Age and Sex, Across the 3 Heart Failure GroupsThe stratified log-rank χ22 was 15.0 (P < .001)
for difference in mortality between groups. HFpEF indicates heart failure with preserved ejection fraction; HFrecEF, heart failure with recovered ejection fraction; and HFrEF, heart failure with reduced ejection fraction.
Figure Legend:
A new HF phenotype 2016
Date of download: 7/11/2016 Copyright © 2016 American Medical Association. All rights reserved.
From: Potential Mortality Reduction With Optimal Implementation of Angiotensin Receptor Neprilysin Inhibitor Therapy in Heart Failure
JAMA Cardiol. Published online June 22, 2016. doi:10.1001/jamacardio.2016.1724
Demonstrated Benefits of Evidence-Based Therapies for Patients With Heart Failure and Reduced Ejection Fraction
Table Title:
Taking the failure out of HF - 2016
• We can prevent the progression of HF
– Greater use of biomarkers & imaging – PREVENTION, diagnosis, prognosis & treatment ;early introduction of
RAAS inhibitors
• GDMT for HFrEF & Quality Improvement
– Still with untapped effectiveness
– Device therapy (ICD/CRT) as indicated; now incl PA monitor?
• New drug therapies-
– LCZ696; Ivabradine
• Personalized Therapy driven by Pharmacogenomics• - NO donors
• Reversal of Disease
– Stem cells (iPS, mesenchymal); Gene Transfer; Growth Factors
– Gene Editing
Questions?
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©2013, American Heart Association 39
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