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Presenters:
Dr. Gregg Fonarow, MD, FACC, FAHA, FHFSA
Dr. Clyde Yancy, MD, MSc, MACC, FAHA, MACP
Dr. Paul Heidenreich, MD, MS, FACC
Clyde W. Yancy, MD, MSc, MACC, FAHA, MACP
Vice Dean, Diversity & Inclusion
Magerstadt Professor of Medicine
Professor of Medical Social Sciences
Chief, Division of Cardiology
Northwestern University, Feinberg School of Medicine
Associate Director, Bluhm Cardiovascular Institute
New Epidemiology
New Therapies
New Guidelines
New Phenotype
From: A Contemporary Appraisal of the Heart Failure Epidemic in Olmsted County, Minnesota, 2000 to 2010
Figure Legend:
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.
315/100,000 to 219/100,000
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
HFpEF HFrEF
Class I, LOE A
ACEI or ARB AND
Beta Blocker
Class I, LOE A
Class I, LOE C Class I, LOE A
Aldosterone
Loop Diuretics Hydral-Nitrates
Antagonist
Neprilysin
Neprilysin inhibition
Inactive metabolites
Cumulative Probability
0.730.87), p<0.001
0.6
0.5
0.4 Enalapril
1117 events (26.5%)
0.3
0.2 Sac/Val
914 events (21.8%)
0.1
0
0 180 360 540 720 900 1080 1260
Days since Randomization
Number at
Risk 4187 3922 3663 3018 2257 1544 896 249
Sac/Val 4212 3883 3579 2922 2123 1488 853 236
Sac/Val = Sacubitril/Valsartan.
Enalapril
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
Sac/Val Enalapril Hazard Ratio p-
(n=4187) (n=4212) (95% CI) Value
Sac/Val = Sacubitril/Valsartan.
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
0.3 0.5 0.7 0.9 1.1 1.3 1.5 1.7 0.3 0.5 0.7 0.9 1.1 1.3 1.5 1.7
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
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
40 Ivabradine (n=3241)
Placebo (n=3264)
Ivabradine
20 793 events (24%)
Ivabradine Placebo
Endpoint HR p-Value
(n=3241) (n=3264)
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
25% 30% 0.82 <0.0001
hospitalization for
non-fatal MI
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 and dose is 2.5 mg twice daily: Discontinue
Pharmacologic Treatment for
Stage C HFrEF
Strategies: HFrEF Stage C
Disease Management NYHA Class I IV
Treatment:
Remote PA monitoring
Process Improvement ? Valsartan/Sacubutril
Patient Education ? Ivabradine
Class I, LOE A
Frailty Assessment ACEI or ARB AND
Beta Blocker
Palliative Care
Genetic Counseling
For persistently symptomatic For NYHA class II-IV patients.
For all volume overload,
African Americans, Provided estimated creatinine
NYHA class II-IV patients
NYHA class III-IV >30 mL/min and K+ <5.0 mEq/dL
Class I, LOE A
Class I, LOE C Class I, LOE A
Aldosterone
Loop Diuretics Hydral-Nitrates
Antagonist
New Guidelines Have Emerged- 2016
COR/LOE 2016
RAASi in Heart Failure and Post-MI LV Dysfunction
PARADIGM-HF
ARNI3
(LCZ-696)
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.
Figure Legend:
Kaplan-Meier Curves, Adjusted for Age and Sex, Across the 3 Heart Failure GroupsThe stratified log-rank 22 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.
Table Title:
Demonstrated Benefits of Evidence-Based Therapies for Patients With Heart Failure and Reduced Ejection Fraction
Greater use of biomarkers & imaging PREVENTION, diagnosis, prognosis & treatment ;early introduction of
RAAS inhibitors
LCZ696; Ivabradine
Gene Editing
Questions?
Thank you!
8/2/2016 2013, American Heart Association 38
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