Heart Failure Care: How World-Class Performance is Within Your Reach

© Health Catalyst. Confidential and Proprietary.
Heart Failure Care: How World Class
Performance is Within Your Reach
John Janas MD, Medical Director, Twistle by Health Catalyst

• Know the key perspectives of the ACC/AHA
CHF management guidelines and current
guideline-directed medical therapy
(GDMT) recommendations.
• Identify gaps in CHF management (GDMT.)
• Understand the challenges of complying
with GDMT.
• Learn how automated communication
pathways can improve patient
engagement and facilitate GDMT.
Objectives

Guideline for the Management of Heart Failure
• Journal:
• A 2022 joint committee report on clinical practice guidelines:
• American College of Cardiology (ACC)
• American Heart Association (AHA)
• Heart Failure Society of America (HFSA)
https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063

Key Perspective 1
• HFrEF (HF with reduced ejection fraction [EF]): LVEF ≤40%.
• HFimpEF (HF with improved EF): Previous LVEF ≤40% and follow-up measurement of
LVEF >40%.
• HFmrEF (HF with mildly reduced EF): LVEF 41%–49%.
• HFpEF (HF with preserved EF): LVEF ≥50%.
*All patients with current or prior HF, irrespective of EF, should be considered for guideline-
directed medical therapy (GDMT).
Classification of Heart Failure

Key Perspective 2
1. Renin-angiotensin system inhibition (RASi) with angiotensin receptor-neprilysin inhibitors
(ARNi), angiotensin-converting enzyme inhibitors (ACEi), or angiotensin (II) receptor blockers
(ARB) alone.
2. Beta blockers.
3. Mineralocorticoid receptor antagonists (MRA).
4. Sodium-glucose cotransporter-2 inhibitors (SGLT2i).
*ARNi is now recommended as first-line RASi to reduce morbidity and mortality in HFrEF (class of
recommendation 1a)
• ACEi is recommended when ARNi is not feasible, and ARB in those who are ACEi intolerant and
when ARNi is not feasible.
• In symptomatic patients with HFrEF who tolerate ACEi or ARB, replacement with ARNi is
recommended for further reduction in morbidity and mortality.
GDMT Has Expanded to Include Four Classes of Medications

Key Perspective 3
• In symptomatic patients with chronic HFrEF,
SGLT2i is recommended to reduce
hospitalization and cardiovascular mortality,
regardless of the presence of type 2 diabetes
(IA).
• SGLT2i can also be beneficial in patients with
HFmrEF and HFpEF (IIA).
New Recommendations Were Made for the Use of SGLT2i in HF
Combined Therapy Effect on All-Cause Mortality in Health
Failure with Reduced Ejection Fraction Across Meta-Analysis
SGLT2i
ARNi
MRA
Beta
Blocker
ARNi
MRA
Beta
Blocker
The addition of SGLT2i
resulted in an additional 12%
decrease in all-cause
mortality.
(HR 0.88, 95% CI 0.78-0.99;
p=0.037)8
56%–63% reduction6–8 41%–61% reduction5,8

Key Perspective 4
• There is little data to guide management of patients with HFimpEF.
• A small, randomized trial (TRED-HF) demonstrated a high rate of relapse of dilated
cardiomyopathy (44%) within 6 months of discontinuation of GDMT.
• Recommendation: GDMT be continued in patients with HFimpEF, including those who
are asymptomatic, to prevent relapse of HF and LV dysfunction.
Managing Patients with HFimpEF

Key Perspective 5
• ARNi, ACEi, ARB, beta blocker, MRA, hydralazine and isosorbide dinitrate in African
Americans, implantable cardioverter-defibrillator (ICD), and cardiac resynchronization
therapy (CRT) are of high value (<$60,000/quality-adjusted life year gained).
• SGLT2i and cardiac transplantation are of intermediate value.
• Tafamadis for amyloid was identified as low value (>$180,000/quality-adjusted life year
gained).
• Mechanical circulatory support and pulmonary pressure monitoring are of uncertain
value.
Relative Value of Therapies

Key Perspective 6
• HF is a progressive disease, as highlighted by the ACC/AHA Stages of HF A–D (next slide).
• New terminology incorporates the designations “at-risk” and “pre-HF.”
• Primary prevention of HF, through lifestyle modification, screening, and management of
risk factors and comorbid conditions, is recommended for those at risk (Stage A) or pre-
HF (Stage B).
HF Classification

ACC/AHA Stages of Heart Failure
Stage A:
At risk for Heart
Failure
Stage B:
Pre-Heart Failure
Stage C:
Symptomatic Heart
Failure
Stage D:
Advanced Heart
Failure
Patients at risk for HF but
without current or
previous symptoms/signs
of HF and without
structural/functional heart
disease or abnormal
biomarkers
Patients with
hypertension, CVD,
diabetes, obesity,
exposure to cardiotoxic
agents, genetic variant for
cardiomyopathy, or family
history of cardiomyopathy
Patients without current
or previous
symptoms/signs of HF but
evidence of 1 of the
following:
Structural heart disease
Evidence of increased
filling pressures
Risk factors and
• increased natriuretic
peptide levels or
• persistently elevated
cardiac troponin in
the absence of
competing diagnoses
Patients with current or
previous symptoms/signs
of HF
Marked HF symptoms that
interfere with daily life and
with recurrent
hospitalizations despite
attempts to optimize
GDMT

Recommendations (Class 1 and 2a) for Patients at Risk of HF (Stage A)
and Those with Pre-HF (Stage B)
Optimal control of BP (1)
Patients with hypertension
At Risk for HF (Stage A)
SGLT2i (1)
Patients with type 2
diabetes and CVD or high
risk for CVD
Optimal management of
CVD (1)
Patients with CVD
Multidisciplinary
evaluation for
management (1)
Patients with exposure to
cardiotoxic agents
Natriuretic peptide
biomarker screening (2a)
Patients at risk for HF
Validated multivariable risk
scores (2a)
Patients at risk for HF
Genetic screening and
counseling (1)
First-degree relatives of
patients with genetic or
inherited cardiomyopathies
ACEi (1)
Patients with LVEF < 40%
Pre-HF (Stage B)
ARB if ACEi intolerant (1)
Patients with a recent MI
and LVEF < 40%
Beta blocker (1)
ICD (1)
> 1 year survival
> 40 days post-MI
Genetic counseling and
testing (2a)
Patients with nonischemic
cardiomyopathy
Continue lifestyle modification and management strategies implemented in Stage A, through Stage B
Figure 5. COR 1 and COR 2a for patients at risk for HF (stage A) and those with pre-HF (stage B) are
shown. Management strategies implemented in patients at risk for HF (stage A) should be continued
though stage B. ACEi indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor
blocker; BP, blood pressure; COR, Class of Recommendation; CVD, cardiovascular disease; HF, heart
failure; ICD, implantable cardioverter-defibrillator; LVEF, left ventricular ejection fraction; MI,
myocardial infarction; and SGLT2i, sodium glucose cotransporter 2 inhibitor.

Trajectory of Stage C HF
• Patients whose symptoms and signs of HF are resolved are still stage C and should be
treated accordingly.
• If all HF symptoms, signs, and structural abnormalities resolve, the patient is considered
to have HF in remission.
• *Full resolution of structural and functional cardiac abnormalities is uncommon.
Newly diagnosed HF,
no previous history of HF
New Onset/De Novo
HF
Persistent HF with ongoing
symptoms/signs and/or
limited functional capacity
Persistent HF
Worsening symptoms/
signs/functional capacity
Worsening HF
Resolution of
symptoms/signs of HF
Resolution of
Symptoms
Stage C with
previous
symptoms of
HF with
persistent LV
dysfunction
HF in
remission
without
resolution of
previous
structural
and/or
functional
heart disease*

Key Perspective 7
The new guideline provides recommendations for select patients with HF and:
• Anemia.
• Iron deficiency.
• Hypertension.
• Sleep disorders.
• Type 2 diabetes.
• Atrial fibrillation.
• Coronary artery disease.
• Malignancy.
Management of Comorbid Conditions May Be Beneficial

Additional Therapies in Patients with HF and Comorbidities
Optimal treatment
according to hypertension
guidelines (1)
Patients with HF and
hypertension
SGLT2i for management of
hyperglycemia (1)
Patients with HF and type 2
diabetes
Surgical revascularization
(1)
Select patients with HF and
LVEF < 35% and suitable
coronary anatomy
Multidisciplinary
evaluation for
management (1)
Patients with HF
attributable to VHD or
cancer therapy
Anticoagulation (1)
Select patients with HF and
AF*
IV iron replacement (2a)
Patients with HFrEF and iron
deficiency
ARB if ACEi intolerant (2a)
Patients with AF and LVEF
< 50%, if rhythm control strategy
fails/not desired and ventricular rates
remain rapid despite medical therapy
Beta blocker (2a)
Patients with HF and symptoms
attributable to AF
CPAP (2a)
Patients with HF with obstructive
sleep apnea
ARB, ACEi, and beta
blockers (2a)
In asymptomatic patients with cancer
therapy-related cardiomyopathy (EF <
50%)
In
addition
to
optimized
GDMT

GDMT Treatment Gap
…based on information obtained from claims data
• Roughly 42% of patients are not prescribed any guideline-directed
medical therapy (GDMT) within 30 days post-index hospitalization, and
45% are prescribed either no oral GDMT or monotherapy within 1 year
post-hospitalization.
• In the management of HF patients with reduced ejection fraction (HFrEF)
in the community, very few receive target doses of oral GDMT.
• Moreover, most patients with HFrEF have no changes made to oral GDMT
over 12 months, despite being discharged on suboptimal doses or no
GDMT.
• It cannot be assumed that oral GDMT will be initiated or optimized after
hospitalization for HFrEF.
Get with the Guidelines

GDMT Across Heart Failure Stages
< 1% of Patients with HFrEF Are on Target Doses Within 12 months of Hospitalization
Stage A:
At risk for Heart Failure
Stage B:
Pre-Heart Failure
Stages C: & D
Symptomatic Heart Failure & Advanced Heart Failure
SGLT2i in patients with
diabetes (1)
SGLT2i in patients with
diabetes (1)
ACEi (1)
ARB if ACEi intolerant (1)
Beta blocker (1)
ARNi in NYHA II-III; ACEi or
ARB in NYHA II-IV (1)
Diuretics, as needed (1) Diuretics, as needed (1)
Beta blocker (1) SGLT2i (2a) SGLT2i (2a)
MRA (1) ACEi, ARB, ARNi (2b) ARNi (2b)
SGLT2i (1) MRA (2b) MRA (2b)
Diuretics, as needed (1) Beta blocker (2b) ARB (2b)
Hydral-nitrates for NYHA
III-IV in African American
patients (1)
HFrEF
LVEF < 40%
HFmrEF
LVEF 41-49%
HFpEF
LVEF > 50%
GDMT
of
major
medication
classes

Treatment of HFrEF Stages C and D
Step 1
• Establish diagnosis
of HFrEF
• Address congestion
• Initiate GDMT
HFrEF
LVEF < 40%
(Stage C)
Step 2
Titrate to target dosing
as tolerated, labs,
health status, and LVEF
Step 3
Consider these patient
scenarios
Step 4
Implement additional
GDMT and device
therapy, as indicated
Step 5
Reassess symptoms,
labs, health status, and
LVEF
Step 6
Referral for HF
specialty care for
additional therapy
ARNi in NYHA II-
III; ACEi or ARB in
NYHA II-IV (1)
Beta blocker (1)
MRA (1)
SGLT2i (1)
Diuretics as
needed (1)
LVEF < 40%,
persistent HFrEF
(Stage C)
LVEF > 40%
HFimpEF
(Stage C)
NYHA III-IV in
African American
patients
NYHA I-III; LVEF
< 35%;
> 1 year survival
NYHA II-III;
ambulatory IV;
LVEF < 35%; NSR
and QRS > 150 ms
with LBBB
Hydral-nitrates
(1)
ICD (1)
CRT-D (1)
Consider
additional
therapies
Refractory HF
(Stage D)
Symptoms
improved
In select patients,
durable MCS (1)
Cardiac
Transplant (1)
Palliative care (1)
(can be initiated
before Stage D)
Investigational
studies*
Continue GDMT with serial reassessment and optimize dosing, adherence and patient education, address goals of care

Renin-Angiotensin System Inhibition Recommendations
ACEi or ARB or ARNi
COR LOE Recommendations
1 A
1. In patients with HFrEF and NYHA class II to III symptoms, the use of ARNi is
recommended to reduce morbidity and mortality.1-5
1 A
2. In patients with previous or current symptoms of chronic HFrEF, the use of
ACEi is beneficial to reduce morbidity and mortality when the use of ARNi is
not feasible.6-13
1 A
3. In patients with previous or current symptoms of chronic HFrEF who are
intolerant to ACEi because of cough or angioedema and when the use of ARNi
is not feasible, the use of ARB is recommended to reduce morbidity and
mortality.14-18
Value Statement:
High Value (A)
4. In patients with previous or current symptoms of HFrEF, in whom ARNi is not
feasible, treatment with an ACEi or ARB provides high economic value.19-25

Renin-Angiotensin System Inhibition Recommendations continued
ACEi or ARB or ARNi
1 B-R
5. In patients with chronic symptomatic HFrEF NYHA class II to III who tolerate
ACEi or ARB, replacement by ARNi is recommended to further reduce
morbidity and mortality.1-5
Value Statement:
High Value (A)
6. In patients with chronic symptomatic HFrEF, treatment with an ARNi instead of
an ACEi provides high economic value.26-29
3: Harm B-R
7. ARNi should not be administered concomitantly with ACEi or within 36 hours
of the last dose of an ACEi.30,31
3: Harm C-LD
8. ARNi should not be administered to patients with any history of
angioedema.32-35
3: Harm C-LD 9. ACEi should not be administered to patients with any history of angioedema.36-
39

Beta Blockers
Beta Blockers
1 A
1. In patients with HFrEF, with current or previous symptoms, use of 1 of the 3
beta blockers proven to reduce mortality (e.g., bisoprolol, carvedilol,
sustained-release metoprolol succinate) is recommended to reduce mortality
and hospitalizations.1-3
Value Statement:
High Value (A)
2. In patients with HFrEF, with current or previous symptoms, beta blocker
therapy provides high economic value.4-8

Mineralocorticoid Receptor Antagonists (MRAs)
MRAs
1 A
1. In patients with HFrEF and NYHA class II to IV symptoms, an MRA
(spironolactone or eplerenone) is recommended to reduce morbidity and
mortality, if eGFR is >30 mL/min/1.73 m2 and serum potassium is <5.0 mEq/L.
Careful monitoring of potassium, renal function, and diuretic dosing should be
performed at initiation and closely monitored thereafter to minimize risk of
hyperkalemia and renal insufficiency.1-3
Value Statement:
High Value (A)
2. In patients with HFrEF and NYHA class II to IV symptoms, MRA therapy
provides high economic value.4-7
3: Harm B-NR
3. In patients taking MRA whose serum potassium cannot be maintained at <5.5
mEq/L, MRA should be discontinued to avoid life-threatening hyperkalemia.8,9

Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i)
SGLT2i
1 A
1. In patients with symptomatic chronic HFrEF, SGLT2i are recommended to
reduce hospitalization for HF and cardiovascular mortality, irrespective of the
presence of type 2 diabetes.1,2
Value Statement:
Intermediate Value (A)
2. In patients with symptomatic chronic HFrEF, SGLT2i therapy provides
intermediate economic value.3-4

Hydralazine and Isosorbide Dinitrate
Hydralazine and Isosorbide Dinitrate
1 A
1. For patients self-identified as African American with NYHA class III-IV HFrEF
who are receiving optimal medical therapy, the combination of hydralazine
and isosorbide dinitrate is recommended to improve symptoms and reduce
morbidity and mortality.1,2
Value Statement:
High Value (B-NR)
2. For patients self-identified as African American with NYHA class III-IV HFrEF
who are receiving optimal medical therapy with ACEi or ARB, beta blockers,
and MRA, the combination of hydralazine and isosorbide dinitrate provides
high economic value.3
2b C-LD
3. In patients with current or previous symptomatic HFrEF who cannot be given
first-line agents, such as ARNi, ACEi, or ARB, because of drug intolerance or
renal insufficiency, a combination of hydralazine and isosorbide dinitrate might
be considered to reduce morbidity and mortality.4,5

Challenges in Complying with GDMT in HF
1. Infrequent office visits.
2. Suboptimal blood pressure management.
3. Discontinuation of medications during
inpatient stays.
4. New medications that add costs and
adherence complexity.

Infrequent Office Visits
• Titrating HF medications to goal
requires daily patient assessments
and monitoring.
• Adjustment of one medication every
1–2 weeks based on BP, symptoms,
and tolerance.
• Cardiologist or Primary Care
Physician rarely sees the patient
every 1–2 weeks.
• NOT practical in current practice/access
to care/workflows.

GDMT Dosing: Sequencing and Uptitration
Sequencing and Uptitration
1 A
1. In patients with HFrEF, titration of guideline-directed medication dosing to
achieve target doses showed to be efficacious in RCTs is recommended, to
reduce cardiovascular mortality and HF hospitalizations, unless not well
tolerated.1–10
2a C-EO
2. In patients with HFrEF, titration and optimization of guideline-directed
medications as frequently as every 1 to 2 weeks depending on the patient’s
symptoms, vital signs, and laboratory findings can be useful to optimize
management.

GDMT Timeline
Ely Gracia. Circulation. Timely Management of New-Onset Heart Failure, Volume: 140, Issue: 8, Pages: 621-623, DOI:
(10.1161/CIRCULATIONAHA.118.035452)

The Evidence for GDMT
Evidence-Based Therapy
Relative Risk Reduction in
All-Cause Mortality in
Pivotal RCTs, %
NNT to Prevent All-Cause
Mortality Over Time*
NNT for All-Cause
Mortality (Standardized
to 12 mo)
NNT for All- Cause
Mortality (Standardized
to 36 mo)
ACEi or ARB 17 22 over 42 mo 77 26
ARNi† 16 36 over 27 mo 80 27
Beta blocker 34 28 over 12 mo 28 9
Mineralocorticoid
receptor antagonist
30 9 over 24 mo 18 6
SGLT2i 17 43 over 18 mo 63 22
Hydralazine or nitrate‡ 43 25 over 10 mo 21 7
CRT 36 12 over 24 mo 24 8
ICD 23 14 over 60 mo 70 23
• ACEi indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor neprilysin inhibitor; CRT, cardiac resynchronization therapy;
HFrEF, heart failure with reduced ejection fraction; ICD, implantable cardioverter-defibrillator; NNT, number needed to treat; RCT, randomized controlled trial; and SGLT2i, sodium-
glucose cotransporter-2 inhibitor.
• *Median duration follow-up in the respective clinical trial.
• †Benefit of ARNi therapy incremental to that achieved with ACEi therapy. For the other medications shown, the benefits are based on comparisons to placebo control.
• ‡Benefit of hydralazine-nitrate therapy was limited to African American patients in this trial.

Suboptimal Blood Pressure Management
• 2017 ACC/AHA BP guidelines lowered the definition of high BP to 130/80 mmHg.
• American College of Physicians (ACP) criticized the 2017 ACC/AHA guidelines, though
stopped short of directing physicians to use its own guideline of 150/90 mmHg.
• Still providers who believe that a “normal” BP in patients with HF who are 60 years or
older is 150/90 mmHg.
2017 Guideline for the Prevention, Detection, Evaluation and Management of
High Blood Pressure in Adults
BP Classification (JNC 7 and ACC/AHA Guidelines)
SBP DBP JNC 7 2017 ACC/AHA
<120 and <80 Normal BP Normal BP
120-129 and <80 Prehypertension Elevated BP
130-139 or 80-89 Prehypertension Stage 1 Hypertension
140-159 or 90-99 Stage 1 Hypertension Stage 2 Hypertension
>160 or >100 Stage 2 Hypertension Stage 2 Hypertension
1. American Heart Association and American
College of Cardiology. (2017, November 13).
High blood pressure redefined for first time in
14 years: 130 is the new high [Press Release].
https://newsroom.heart.org/news/high-blood-
pressure-redefined-for-first-time-in-14-years-
130-is-the-new-high
2. Phend, C. ACP criticizes new blood pressure
guideline – changes went too far on too little
evidence, group says. MedPageToday. 2018, Jan
22.
https://www.medpagetoday.com/cardiology/hy
pertension/70677
3. Phend, C. Primary care orgs favor looser BP
targets in older adults – controversial 150 mm
Hg threshold advocated for low- to average-risk
seniors. MedPageToday. 2017, Jan 16.
https://www.medpagetoday.com/cardiology/hy
pertension/62559

Key Perspective 8
ACC/AHA CHF Guidelines Recommend that BP Is Managed to Less than 130/80
mmHg, if Tolerated by Patient, Regardless of Age

SPRINT (Systolic Blood Pressure Intervention Trial)
Control to an SBP goal <120 mm Hg
(compared with an SBP goal of <140 mm
Hg).
• Decreased incidence of HF by 38%.
• Reduced mortality by 23%.
• Upadhya B, Rocco M, Lewis CE, et al. Effect of intensive blood pressure treatment on heart failure events in the Systolic Blood Pressure Reduction Intervention Trial. Circ Heart Fail.
2017;10:e003613.
• SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103–2116.

Discontinuation of HF Medications During Inpatient Stays
• Acute CHF (decompensation) symptoms: Volume/fluid overload (congestion).
• Treatment: Aggressive diuresis.
• Result:
• Fluid shifts.
• Decreased BP.
• Decreased renal blood flow.
• Increased creatinine.
• Reaction: Discontinuing GDMT to ensure stabilization and facilitate discharge,
despite clinical evidence to the contrary.
• Gilstrap LG, Fonarow GC, Desai AS, Liang L, Matsouaka R, DeVore AD, Smith EE, Heidenreich P, Hernandez AF, Yancy CW, Bhatt DL. Initiation, continuation, or withdrawal of
angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers and outcomes in patients hospitalized with heart failure with reduced ejection fraction. Journal of the American
Heart Association. 2017 Feb 11;6(2):e004675.
• Prins KW, Neill JM, Tyler JO, Eckman PM, Duval S. Effects of beta-blocker withdrawal in acute decompensated heart failure: a systematic review and meta-analysis. JACC: Heart Failure.
2015 Aug;3(8):647-53.

Maintenance or Optimization of GDMT During Hospitalization
Maintenance or Optimization of GDMT During Hospitalization
1 B-NR
1. In patients with HFrEF requiring hospitalization, preexisting GDMT should be
continued and optimized to improve outcomes, unless contraindicated.1–5
1 B-NR
2. In patients experiencing mild decrease of renal function or asymptomatic
reduction of blood pressure during HF hospitalization, diuresis and other
GDMT should not routinely be discontinued.6–11
1 B-NR
3. In patients with HFrEF, GDMT should be initiated during hospitalization after
clinical stability is achieved.2,3,5,12–18
1 B-NR
4. In patients with HFrEF, if discontinuation of GDMT is necessary during
hospitalization, it should be reinitiated and further optimized as soon as
possible.19–22

Inpatient GDMT Sequencing
https://www.acc.org/latest-in-cardiology/articles/2022/06/01/12/11/inpatient-initiation-of-hfref-
therapies
Day of Admission Day of Discharge
ARNi*
Beta Blocker
MRA
SGLT2i
Safe in ADHF
Close monitoring of K and SCr
Can start Metoprolol Tartrate for rapid titration, change to evidence-
based BB upon discharge
Safe in ADHF, better tolerated in hyper- or euvolemic patients
Close follow-up for
continued titration
to target or
maximally tolerated
dosing. Monitor BP,
HR, K, and SCr
periodically.
*ARNi is preferred if tolerated and affordable, but can consider ACEi/ARB therapy
ADHF = Acute decompensated heart failure; SCr = Serum creatinine

New Medications Add Cost and Adherence Complexity
• Cost
• 30-day supply of Entresto® (sacubitril/valsartan)
• Retails for $817 without insurance.
• Those with Medicare Part D pay less than $50 per month, which may still deter patient
adherence.
• Safe Transition of Medications
• ACEis such as lisinopril (Zestril), enalapril (Vasotec), and benazepril (Lotensin), must
be stopped for 36 hours before initiating ARNis or the risk of angioedema

New Medications Add Cost and Adherence Complexity continued
• ACC/AHA/HFSA guidelines include recommendations SGLT2is like Farxiga
(Dapagliflozin) and Jardiance (Empagliflozin).
• Multiple studies have documented their cost effectiveness.
• SGLT2is are expensive and not always on formulary, covered by insurance, or
incur higher co-pays.
• ARNis nor SGLT2is are generic and can be of considerable cost to patients, yet
both therapies provide high economic value.
• Significant reduction in hospitalizations and increased survival for patients with both
HFrEF and HFpEF.
Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Furtado RH, Bhatt DL. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and
renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. The Lancet. 2019 Jan 5;393(10166):31-9.

Strategies to Reduce Patients’ Cost of Care
Coordinate care (including labs and imaging) among
clinicians to minimize unnecessary duplication.
Consider limitations of medication coverage (insurance,
Medicaid, etc.) when prescribing.
Use generic equivalents for GDMT whenever possible.
Work with a pharmacist, social worker, or patient navigator
to identify and navigate Patient Assistance Programs.
Request price matching if a drug is found at a lower cost at
another pharmacy.

Target Dose = Maximally Tolerated Dose
• To achieve the maximal benefits of
GDMT in patients with chronic HFrEF,
therapies must be initiated and titrated
to maximally tolerated doses.
• Doses of GDMT higher than those
studied in randomized clinical trials,
even if tolerated, are not known to
provide incremental benefits, and are
generally not recommended.

Drugs Commonly Used to Treat HFrEF
Drug Initial Daily Dose(s) Target dose(s)
Angiotensin converting enzyme inhibitor (ACEI)
Captopril 6.25 mg 3 times daily 50 mg 3 times daily
Enalapril 2.5 mg twice daily 10–20 mg twice daily
Fosinopril 5–10 mg once daily 40 mg once daily
Lisinopril 2.5–5 mg once daily 20–40 mg once daily
Perindopril 2 mg once daily 8-16 mg once daily
Quinapril 5 mg twice daily 20 mg twice daily
Ramipril 1.25–2.5 mg once daily 10 mg once daily
Trandolapril 1 mg once daily 4 mg once daily
Angiotensin receptor blocker (ARB)
Candesartan 4–8 mg once daily 32 mg once daily
Losartan 25–50 mg once daily 50–150 mg once daily
Valsartan 20–40 mg once daily 160 mg twice daily
Angiotensin receptor-neprilysin inhibitor (ARNI)
Sacubitril-valsartan 49 mg sacubitril and 51 mg valsartan twice
daily (therapy may be initiated at 24 mg
sacubitril and 26 mg valsartan twice daily)
97 mg sacubitril and 103 mg valsartan
twice daily

Drugs Commonly Used to Treat HFrEF continued
Drug Initial Daily Dose(s) Target dose(s)
Beta Blockers
Bisoprolol 1.25 mg once daily 10 mg once daily
Carvedilol 3.125 mg twice daily 25–50 mg twice daily
Carvedilol CR 10 mg once daily 80 mg once daily
Metoprolol CR/XL 12.5–25 mg once daily 200 mg once daily
Mineralocorticoid receptor antagonists (MRA)
Spironolactone 12.5–25 mg once daily 25–50 mg once daily
Eplerenone 25 mg once daily 50 mg once daily
Sodium glucose cotransporter 2 inhibitor (SGLT2I)
Dapagliflozin 10 mg once daily 10 mg once daily
Empagliflozin 10 mg once daily 10 mg once daily
Isosorbide dinitrate and hydralazine
Fixed dose combination 20 mg isosorbide dinitrate and 37.5 mg
hydralazine 3 times daily
40 mg isosorbide dinitrate and 75 mg
hydralazine 3 times daily
Isosorbide dinitrate and hydralazine 20–30 mg isosorbide dinitrate, and
25–50 mg hydralazine 3–4 times daily
120 mg isosorbide dinitrate total daily in
divided doses, and 300 mg hydralazine total
daily in divided dose
If Channel inhibitor
Ivabradine 5 mg twice daily 7.5 mg twice daily
Soluble guanylate cyclase stimulator
Vericiguat 2.5 mg once daily 10 mg once daily
Digoxin 0.125–0.25 mg daily (modified according to
monogram)
Individualized variable dose to achieve serum
digoxin concentration 0.5–<0.9 ng/mL

Key Perspective 9
• Attempt to achieve target doses of all
recommended therapies in the absence of
contraindications and/or intolerance.
• Titration should occur even if the patient
appears stable or their symptoms and/or
EF improve.
Target Doses Are Associated with Best Outcomes

Use of Technology to Optimize GDMT
Performance Data Critical to Demonstrating Compliance with GDMT, Gain Buy-In

Training and Detailed Protocols Reduce Barriers to Compliance
• The order in which each medication class is
titrated to goal.
• Frequency of titration.
• Physiologic parameters and assessment details
that must be met before a medication dose is
adjusted.
• Specific dose adjustments that will be made
with each change.
• Assessment parameters and frequency of
collection after each medication adjustment.

Detailed Protocols and Algorithms
• Process for managing side effects.
• Data parameters that will trigger alerts to the care team.
• Timeliness and processes for human intervention, when required.
• Escalation processes for technical and clinical concerns.
• Ongoing evolution of protocols and algorithms based on patient outcomes and
provider experiences.
• Reporting and metric analysis and sharing across providers.

Designated Staff to Manage Data Verification and Patient Outreach
• Technology can offload a great deal of the
routine communication and management of
HF medication titration.
• Success program requires trained clinical staff.
• Nurse navigators/coordinators, physician
assistants, pharmacists, or nurse practitioners.
• Initiate each patient’s care protocol – typically
after a care transition or office visit in which
medications have been reconciled.
• Manage alert escalations that may warrant
intervention such as a low BP or symptoms of
worsening HF.

Target Doses May Not Be Achievable
• Patients that are older than the average age for clinical trials.
• Side effects (hypotension).
• Comorbidities (CKD, Diabetes, Hyperkalemia*).
• *Newer potassium binders (patiromer and sodium zirconium cyclosilicate).
• “…data are lacking, it is logical to assume that below-target doses of multiple
classes of GDMT are likely more effective in reducing risk than large doses of 1 or
2 agents.”
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.04.025

Monitor Patient Response and Adjust Accordingly
• Decrease in eGFR of >30% or the development of hyperkalemia.
• A reduction in doses may be necessary.
• Short-term changes in eGFR during intense diuretic therapy or with the initiation
of an ACEi or ARB do not predict longer-term adverse outcomes.
• Initial mild worsening of renal function after SGLT2i initiation may also occur
before longer-term renal function preservation.
• If evidence of hypovolemia, the dose of diuretic agents should be reduced.
• ARNi dose may also need to be reduced in the setting of renal insufficiency or
hypotension.
• Hyperkalemia may require changes in medical therapy.
• Newer potassium binders (patiromer and sodium zirconium cyclosilicate).
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.04.025

Diligent Management of Volume Status Will Reduce Patient Symptoms
Avoid the Vicious Cycle: Congestion  Symptoms
 Hospitalizations
Use remote physiologic monitoring (RPM) and
patient engagement tools to:
• Collect daily wright, BP, and pulse.
• Gather symptom assessments.
• Escalate as appropriate.
• Deliver automated alerts to care team and/or
algorithm (standing orders) to patient with care
team alerts by exception.

Tolerability and Side Effects Depend, In Part, on How and When GDMT
Is Prescribed
• Use lower target doses of an
ARNi/ACEi/ARB and discontinue
aldosterone antagonist if estimated
creatinine clearance 5.0 mEq/L.
• Available data support a survival
benefit even with a low-dose ACEi,
which may be the default choice in
the setting of renal insufficiency and
marginal blood pressure.
• Check for over-diuresis, use of non-
CV drugs with hemodynamic effects
(e.g., anticholinergic agents,
treatments for prostate enlargement,
others), autonomic dysfunction, or
simultaneous administration of
multiple HF medications.
• EXCLUDE all the above BEFORE
decreasing dose of GDMT
• Use best-tolerated doses of GDMT.
Symptomatic Hypotension
Worsening Renal Function or
Hyperkalemia

Tools That Effectively Engage Patients
• Embraced by a large portion of the patient
population.
• Overcomes barriers: Access to broadband or
cellular coverage.
• Flexible devices for both communication and
remote physiologic monitoring (RPM).
• Rapid response to patient-entered data.
• Educational content: Easy to
access/understand, in engaging formats.
• Videos and infographics.
• Motivational content: Encourage patient self-
management and change behavior.

Patient Engagement Pathways for GDMT Optimization in HF
• Pre-discharge – during acute inpatient episode.
• Post-discharge – first 2 weeks.
• After provider follow-up visit.
• Titration and/or addition of medications.
• HF prevention and risk factor reduction.

Pre-Discharge – During Acute Inpatient Episode Pathway
Topics:
• The concept of GDMT.
• The rationale for the need to take
medications across four different drug
classes.
• How they work to improve heart function.
• Their impact on morbidity, mortality, and
quality of life.
• The process that will be used to adjust
medications over time.

Pre-discharge – During Acute Inpatient Episode Pathway continued
• Social determinants of health (SDOH) that
may impact care inequities.
• The presence and use of RPM devices in the
home .
• Initiation of the acquisition of required
devices, if appropriate.
• Education and instruction on proper use by
patient and/or caretaker(s).
• Medication prescriptions on hand.
• Alerts to care team for needed discharge
prescriptions.
• Alerts to the insurer.

Goals of the Post-Discharge Pathway
• Support the patient until they see their primary care provider or cardiologist (up
to two weeks, but ideally within 5–7 days).
• Monitor patient progress.
• Facilitate re-initiation of medications that were discontinued during the inpatient
visit, as well as the initiation of newly prescribed medications.
• Medication Reconciliation process in which therapies are continued, resumed,
initiated, or discontinued.

Post-Discharge – First 2 Weeks Pathway
Topics
• Daily symptom assessments, blood pressure readings,
and weight.
• Alerts to the care team when values demonstrate
deterioration to facilitate timely intervention.
• Validation that the patient has resumed medications
that were held in the inpatient setting, as ordered .
• If an ACEi was held during an inpatient stay and the
provider would like to substitute an ARNi, the pathway
will validate that the patient has not resumed the ACEi
and provide instructions on how to begin ARNi therapy.

Post-Discharge – First 2 Weeks Pathway continued
• Validation that the patient has possession of newly
initiated post-discharge medications and has initiated
therapy.
• Assessments monitor patient response to the new
medication and alert care teams if intervention is
required.
• Reminders about upcoming tests and appointments.
• Continuing education.
• Post-discharge transition of care.
• HF disease process.
• Compliance with GDMT.
• Lifestyle modification strategies, including dietary
restrictions and physical activity.

Goal of the Post-Provider Follow-Up Pathway
• Titrate HF medications to goal across the first of four drug classes.
• *Initiated unless contraindications for specific medications are documented.
• Care Team (pharmacist, nurse navigator/coordinator, physician assistant, or nurse
practitioner) must:
• Enter the current medication(s) and dose(s) in the patient engagement tool (unless
integrated with the EHR).
• Enter target medication(s) and dose(s) to launch the appropriate pathway.

After Provider Follow-Up Visit Pathway
Topics
• Ensuring acquisition of prescribed ARNi, ACEi,
or ARB medication(s).
• Daily symptom assessments: heart rate, BP and
weight (change noted).
• Alerts sent to the care team when values
demonstrate deterioration.
• Continuing education
• HF disease process.
• Compliance with GDMT.
• Lifestyle modification strategies, including
dietary restrictions and physical activity.

After Provider Follow-Up Visit Pathway continued
• Titration of medication to target dose.
• If stable, then every 1–2 weeks, patients instructed
to double their dose until target goal is reached or
to a maximum tolerated dose.
• If BP remains above 90/50 mmHg (or alternate value
as desired) and they are asymptomatic, then titration
continues until optimal dose achieved or symptoms
occur.
• Once target dose of the ACEi, ARB, or ARNi is
achieved, provider is electronically notified and
asked to confirm initiation of the next pathway.
• The patient’s medication profile is automatically
updated in the EHR with the final medication dose.

After Provider Follow-Up Visit Pathway continued
• Reminders about upcoming tests and
appointments.
• Collection and scoring of patient-reported
outcomes measures (PROMs) such as:
• Seattle Angina Questionnaire-7 (SAQ-7).
• Rose Dyspnea Scale.
• Patient Health Questionnaire-2.
• Any other PROM used by the organization.

Titration and/or Addition of Medications
Once the ACEi, ARB, or ARNi medication(s) have
been optimized, subsequent pathways initiate
and/or titrate medications for the other three drug
classes in a similar fashion:
• Beta blockers
• MRA
• SGLT2I

Facilitating Care Management
• Documentation of the patient engagement,
interventions, and care plan adjustments
automatically returned to the EHR (or document
of record) to facilitate support of
documentation for Chronic Care Management
(CCM) billing.
• At the conclusion of each pathway:
• Provider is notified of the progress that has
been made in achieving GDMT goals.
• Patient’s medication profile is updated in the
EHR.

Corollary Pathways to Address High Risk Characteristics
• Comorbid conditions such as renal dysfunction,
pulmonary disease, diabetes, mental health,
and substance use disorders.
• Limitations in psychosocial support.
• Impaired health literacy, cognitive impairment.
• Additional surgical or device therapy .
• Cardiac rehabilitation.

Heart Failure Prevention Through Risk Factor Reduction
• Controlling BP pathway.
• Transdermal optical imaging.
• Cardiovascular risk assessment and BP
screening.
• Prediabetes screening and management
pathways.
• Statin medication adherence pathway.
• Chronic kidney disease (CKD) screening and
management pathway.

Call to Action
• Implement key perspectives of the ACC/AHA HF management guidelines and
current GDMT recommendations.
• Reduce gaps in HF management (GDMT).
• Address the challenges of complying with GDMT.
• Develop and implement automated communication pathways to improve patient
engagement and facilitate GDMT.
Modify Your Organization’s Heart Failure Journey

Heart Failure Care: How World-Class Performance is Within Your Reach

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