HF2019
HF2019
HF2019
Reviewed by Orly Vardeny, Pharm.D., FCCP, FAHA, FHFSA, BCACP; Stephen B. Vickery, Pharm.D., BCPS;
and Kevin Ordons, Pharm.D., BCPS, BCCP
LEARNING OBJECTIVES
1. Apply treatment strategies to reduce the progression of heart failure (HF) through assessing functional class.
2. Evaluate and justify traditional and newer treatment strategies for patients with stage C HF, specifically as they relate to
the 2017 guideline updates.
3. Develop treatment strategies for patients with stage D HF.
4. Evaluate treatment strategies for potential benefit/harm for the patient with HF with preserved ejection fraction.
INTRODUCTION
ABBREVIATIONS IN THIS CHAPTER
Current Status of Heart Failure
ACC/AHA
American College of Cardiology/
American Heart Association Statistics
AF Atrial fibrillation The prevalence of heart failure (HF) continues to be a significant bur-
ARNI Angiotensin receptor-neprilysin den, not only for the families and individuals who take care of these
inhibitor
patients but also for the health care system as a whole. With a reported
BNP B-type natriuretic peptide
915,000 new cases of HF diagnosed annually, 6.5 million Americans
CRT Chronic resynchronization therapy
20 years and older had a diagnosis of HF in 2011–2014 (Benjamin
CV Cardiovascular
2018). Despite significant efforts to identify and treat the underlying
GDMT Guideline-directed management
risk factors that may prevent HF, projections suggest that by 2030,
and therapy
HF cases will increase by 46%, totaling 8 million people (Heidenreich
HF Heart failure
2013). About 1%–2% of the adult population (in developed countries)
HFpEF Heart failure with preserved ejec-
tion fraction has a diagnosis of HF, which increases with advanced age (Ponikow-
HFrEF Heart failure with reduced ejection ski 2016). Patients of African American heritage have the highest risk
fraction of developing HF, followed by those of Hispanic/Latino ethnicity and
ICD Internal cardiac defibrillator whites. African American patients are believed to be at high risk of
LV Left ventricular developing HF because of a lower socioeconomic status and higher
LVAD Left ventricular assist device prevalence of risk factors (Ponikowski 2016).
MRA Mineralocorticoid receptor The economic burden of HF is of vast concern, with a reported
antagonist cost of $30.2 billion in 2012 and an anticipated cost increase by
RAAS Renin-angiotensin-aldosterone almost 130%, reaching $69.7 billion by 2030 (Heidenreich 2013).
system Efforts are under way to further explain risk factors and implement
strategies to manage risk factors and associated disease preven-
Table of other common abbreviations.
tion. However, despite an improved understanding of HF pathophys-
iology, risk factors, and management strategies, data are conflicting
on overall survival after an HF diagnosis. Compared with other termi-
nal diseases, HF survival remains unacceptably low. According to an
Oxford report, cancer survival has doubled, whereas HF survival has
not changed over the same period (Taylor 2017).
Ideally, a risk stratification score could be applied to an individ-
ual patient to help guide clinicians in treatment as well as to provide
CAD = coronary artery disease; DM = diabetes mellitus; EF = ejection fraction; HF = heart failure; HTN = hypertension; N/A = not
applicable.
Information from: Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for
the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical
Practice Guidelines and the Heart Failure Society of America. Circulation 2017;136:e137-61.
Beyond its potential diagnostic capabilities, BNP can serve medications for diabetes (e.g., sulfonylureas, thiazolidinedi-
as a prognostic marker in both patients with chronic HF and ones) or arthritis (e.g., NSAIDs) can exacerbate HF symptoms.
patients with acute decompensated HF. A systematic review Pharmacists treating patients with HF must actively review
using BNP as a prognostic marker showed that for every patients’ medications to avoid unwarranted complications.
100-pg/mL increase in BNP, the relative risk of mortality was Anemia is common in patients with HF, but its overall
increased by 35% (Doust 2005). However, even GDMT may not prevalence varies within the literature. Symptoms associ-
offset the risk of mortality in patients with persistently ele- ated with anemia commonly parallel those associated with
vated BNP concentrations. HF (dyspnea and fatigue) and occur because of reduced oxy-
A new recommendation from the ACC/AHA 2017 guideline gen delivery to tissues. Although the cause of anemia is likely
pertains to the use of pre-discharge BNP concentrations as multifactorial, it may include decreased intake and/or absorp-
a prognostic marker for rehospitalizations or risk of death. tion of iron, creating iron-deficiency anemia. Alterations in GI
Studies have shown a strong correlation between patients absorption can result from intestinal edema, use of medica-
with higher BNP concentrations at discharge and those who tions altering gastric pH (e.g., proton pump inhibitors or his-
did not have a reduction in BNP concentrations with respect tamine-2 antagonists), or ingestion of foods that may reduce
to subsequent mortality or readmission (Logeart 2004). absorption (e.g., calcium, tannins, phosphates, antacids).
Despite the potential usefulness of BNP concentrations as a Controversy continues to surround the role of inflammation
prognostic marker, the current guidelines posit that targeting in chronic diseases because of conflicting data. Of particular
certain concentrations or a relative change may be unpracti- importance are the negative clinical consequences that stem
cal and potentially harmful to patients. from iron deficiency in patients with HF. Most notably, stud-
ies have shown an increase in all-cause mortality in patients
Comorbidity Management in HF
with a concomitant iron deficiency and HF independently of
Anemia anemia (Okonko 2011). In a meta-analysis of five prospective
Beyond optimizing GDMT, comorbidity management can studies, intravenous iron therapy was evaluated for its effect
help improve quality of life and avoid complications. Certain on death and hospitalizations in patients with heart failure
Drug Starting Dose Target Dose Mean Dose Achieved in Clinical Trial
Ivabradine 5 mg BID 7.5 mg BID 6.4 mg BID (28 days) and 6.5 mg BID
(1 year)
a
Total dose of both components as defined in the PARADIGM-HF study.
b
African American patients who remain symptomatic despite receiving GDMT.
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; ARNI = angiotensin receptor-neprilysin
inhibitor; BID = twice daily; GDMT = guideline-directed management and therapy; HF = heard failure; LOE = level of evidence; MRA =
mineralocorticoid receptor antagonist; QD = once daily; QID = four times daily; TID = three times daily.
Information from: Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for
the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical
Practice Guidelines and the Heart Failure Society of America. Circulation 2017;136:e137-61.
The adverse effect profile of ACEIs is primarily reflected rare, complication of ACEI therapy is angioedema. Within the
in direct or indirect inhibition of AngII formation or because ONTARGET clinical trial, angioedema occurred in only 0.3%
of increased bradykinin concentrations (Table 3). Common of 8500 patients treated with ramipril (ONTARGET Investiga-
adverse events include hypotension, hyperkalemia, worsen- tors 2008). Patients who develop angioedema while receiv-
ing renal function, and dry cough. The most severe, albeit ing ACEI therapy should avoid being rechallenged, given the
Compensatory
Mechanism
Affected Drug Class Mechanism of Action Adverse Effects (common) Monitoring Values
AngII = angiotensin II; BP = blood pressure; cGMP = guanosine 3’5’-monophosphate; HF = heart failure; RAAS = renin-angiotensin-al-
dosterone system.
concern for recurrence. To limit the risk of adverse effects, trials. Monitoring should occur after initiating therapy and
ACEI therapy should be titrated after at least 2 weeks. Clinical after dose escalations.
laboratory values and adverse effects should be monitored
after each titration. Aldosterone Receptor Antagonist Therapy
Mineralocorticoid receptor antagonists have been used
ARB Therapy across the HF spectrum, providing benefits through inhibit-
Angiotensin receptor blockers were developed with the idea ing aldosterone’s activities. Clinical studies have shown sur-
that inhibiting AngII through blockade of the AngII type 1 vival benefits when MRAs are used in patients with advanced
receptor could further improve HF. The current guidelines HF (spironolactone) and patients after an MI with a reduced
recommend that either an ACEI or an ARB be used, with EF (eplerenone). Use of MRAs in patients with mild-moderate
ARBs preferred if patients cannot tolerate an ACEI. Unlike HF was studied in the EMPHASIS-HF study. Patients were
ACEI therapy, whose benefits are considered universal well matched at randomization, with 93% of study partici-
across the drug class, the following ARBs are listed for use pants taking an ACEI or an ARB (or both) and 86% receiving
within the current guidelines: candesartan, valsartan, and β-blockers. Like within the RALES study, the overwhelm-
losartan. ing benefit of eplerenone in addition to GDMT prompted
Angiotensin receptor blockers are generally well toler- the study to be prematurely terminated because of a 37%
ated and have an adverse effect profile similar to ACEIs, with reduction in the composite primary end point: risk of death
a noted reduction in the rates of cough and angioedema and hospitalization for HF compared with placebo (Zannad
but an apparent increased rate of hypotension. Titration of 2011). Patients were initiated on eplerenone 25 mg/day with
ARBs should be similar to that of ACEIs, with initiation at low a dose increase at 4 weeks to a goal dose of 50 mg/day (or in
doses and increasing doses similar to those used in clinical patients with an estimated glomerular filtration rate [eGFR]
of 30–49 mL/minute/1.73 m2, study investigators initiated
1. C ohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med
2001;345:1667-75.
2. M cMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004.
3. P feffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left
ventricular dysfunction, or both. N Engl J Med 2003;349:1893-906.
4. Y ancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart
failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the
Heart Failure Society of America. Circulation 2017;136:e137-61.
Digoxin Ivabradine
Mechanism of HFrEF: Inhibition of Na/K channel leading to Inhibition of the If channels within the sinoatrial node
action increased intracellular calcium and contractility leading to prolonged diastolic depolarization and a
Arrhythmias: AV nodal suppression reduction in heart rate
Clinical benefits HFrEF: Improvement in symptoms and exercise HFrEF: Reduce the risk of hospitalizations in patients
tolerance with reduction in HF hospitalizations with stable HF with heart rate ≥ 70 beats/min in NSR
Appropriate use Consider in symptomatic patients who are Patient with stable HFrEF in NSR with heart rate ≥
currently treated with ACEI/ARB and β-blocker 70 beats/min on maximally tolerated β-blocker
May be considered in patients with symptomatic
HFrEF with concomitant AF when alternative
options cannot be pursued
AF = atrial fibrillation; AV = atrioventricular; HFrEF = heart failure with reduced ejection fraction; NSR = normal sinus rhythm; SVT =
supraventricular tachycardia.
had mixed results, with a reduction in major CV events and Patients should avoid non-dihydropyridine CCBs (diltiazem,
death in some trials that was not replicated in other cases. verapamil) because of their potential harm in those with symp-
To further ascertain potential benefits of anticoagulation in tomatic HFrEF. Patients in the Multicenter Diltiazem Post
these high risk patients, the COMMANDER-HF study evalu- Infarction Trial (MDPIT) initiated on diltiazem were at a sig-
ated rivaroxaban in HFrEF patients with no history of AF. Par- nificant risk of developing congestive HF compared with pla-
ticipants were randomized to rivaroxaban (2.5 mg twice daily) cebo (p=0.0017) (Goldstein 1991). The dihydropyridine CCBs
or placebo with the hypothesis that the study medication amlodipine and felodipine appear to be safe in both patient
would lead to a reduction in death and CV events. Following a subsets with HF, but given their lack of benefit, they should be
median follow-up period of 21.1 months, the authors found no reserved for select patients already receiving GDMT (HFrEF)
difference in the rate of death, MI or stroke (rivaroxaban: 25% or in patients whose hypertension is inadequately controlled
vs placebo: 26.2%, HR 0.94, 95% CI 0.84-1.05; p=0.27). There with an ACEI/ARB or β-blocker.
was no difference in the primary composite safety outcome
OTC Medications
(fatal bleeding or bleeding into a critical space) but a signifi-
cant increase in the risk of ISTH-defined major bleeding was Nonsteroidal Anti-inflammatory Drugs
noted within the rivaroxaban cohort (3.3% vs 2%, HR 1.68, 95% Nonsteroidal anti-inflammatory drugs are commonly used
CI 1.18-2.39; p=0.003). Overall, current data do not support the in the general population because of their anti-inflammatory
routine use of anticoagulation in patients with HFrEF and no and analgesic properties. Inhibition of renal prostaglandins
other compelling indication. Of greater concern is the risk of leads to vasoconstriction of the afferent arteriole and sub-
complications, specifically the risk of major bleeding without sequent increase in sodium and water resorption. Although
a significant benefit for therapy. generally well tolerated in healthy individuals, NSAIDs should
As with warfarin, no available evidence suggests any ben- be avoided in patients with HF, given their propensity to
efit of antiplatelet therapy in patients with HF without con- worsen kidney function and raise blood pressure (through
comitant disease necessitating therapy (e.g., coronary sodium and water retention), thereby opposing the diuretic
artery disease). Because of the associated increased risk of therapy. Heart failure exacerbations and increased mortality
GI bleeding when using antiplatelet therapy, its routine use, have occurred in observational cohort studies that evaluated
except in ischemic cardiomyopathy, is not recommended. selective or nonselective NSAID therapy.
Gheorghiade M, Bohm M, Greene SJ, et al. Effect of aliskiren Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid mea-
on postdischarge mortality and heart failure readmissions surement of B-type natriuretic peptide in the emergency
among patients hospitalized for heart failure: the ASTRO- diagnosis of heart failure. N Engl J Med 2002;347:161-7.
NAUT randomized trial. JAMA 2013;309:1125-35.
Marso SP, Bain SC, Consoli A, et al.; for the SUSTAIN-6
Goldstein RE, Boccuzzi SJ, Cruess D, et al. Diltiazem Investigators. Semaglutide and cardiovascular out-
increases late-onset congestive heart failure in post comes in patients with type 2 diabetes. N Engl J Med
infarction patients with early reduction in ejection frac- 2016;375:1834-44.
tion. The Adverse Experience Committee; and the Mul-
ticenter Diltiazem Post-infarction Research Group. Marso SP, Daniels GH, Brown-Frandsen K, et al.; for the
Circulation 1991;83:52-60. LEADER Steering Committee on behalf of the LEADER
Trial Investigators. Liraglutide and cardiovascular out-
Green JB, Bethel MA, Armstrong PW, et al.; for the TECOS comes in type 2 diabetes. N Engl J Med 2016b;375:311-22.
Study Group. Effect of sitagliptin on cardiovascular out-
comes in type 2 diabetes. N Engl J Med 2015;373:232-42. Martin RI, Pogoryelova O, Koref MS, et al. Atrial fibrillation
associated with ivabradine treatment: meta-analysis of
Greene SJ, Butler J, Albert NM, et al. Medical therapy randomised controlled trials. Heart 2014;100:1506-10.
for heart failure with reduced ejection fraction: the
CHAMP-HF Registry. J Am Coll Cardiol 2018;72:351-66. Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in
patients with heart failure and preserved ejection fraction.
SPRINT ResearchGroup, Wright JT Jr, Williamson JD, et al. A N Engl J Med 2008;359:2456-67.
randomized trial of intensive versus standard blood pres-
sure control. N Engl J Med 2015;373:2103-16. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-nepri-
lysin inhibition versus enalapril in heart failure. N Engl J
Guazzi M, Vicenzi M, Arena R, et al. Pulmonary hypertension Med 2014;371:993-1004.
in heart failure with preserved ejection fraction: a target of
phosphodiesterase-5 inhibition in a 1-year study. Circula- Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchroni-
tion 2011;124:164-74. zation therapy for the prevention of heart-failure events.
N Engl J Med 2009;361:1329-38.
Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the
impact of heart failure in the United States: a policy state- Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and car-
ment from the American Heart Association. Circ Heart Fail diovascular and renal events in type 2 diabetes. N Engl J
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Hoendermis ES, Liu LC, Hummel YM, et al. Effects of silde- Nizamic T, Murad H, Allen LA, et al. Ambulatory inotrope infu-
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pulmonary hypertension: a randomized controlled trial. O’Connor CM, Starling RC, Hernandez AF, et al. Effect of
Eur Heart J 2015;36:2565-73. nesiritide in patients with acute decompensated heart fail-
ONTARGET Investigators, Yusuf S, Teo KK, et al. Telmisar- ure. N Engl J Med 2011;365:32-43.
tan, ramipril, or both in patients at high risk for vascular Okonko DO, Mandal AK, Missouris CG, et al. Disordered iron
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A. Fish oil 28. A 45-year-old man has newly diagnosed HF and a med-
B. Aspirin ical history of hypertension and diabetes. His initial
C. Ibuprofen ECHO reveals heart failure with preserved ejection frac-
D. Caffeine tion (HFpEF) (LVEF 55%). His current medication ther-
apy includes hydrochlorothiazide 25 mg daily, metformin
1000 mg twice daily, furosemide 20 mg daily (as needed),
Questions 26 and 27 pertain to the following case.
and aspirin 81 mg daily. His diabetes and hyperten-
H.M. is a 65-year-old white man with a medical history of MI
sion have been well controlled with this regimen, with
(15 years ago) that required stent placements and subse-
an A1C of 6.5% and blood pressure of 114–125 systolic
quent three-vessel bypass surgery. Additional medical his-
and 65–75 diastolic. Important laboratory values include
tory includes diabetes and gout. After his MI, H.M.’s heart
K 4.1 mEq/L and SCr 1.1 mg/dL. The patient reports
function slowly deteriorated until he developed systolic dys-
increased swelling with a 3-lb weight gain over the past
function. He has been seen in the HF clinic for several years
2–3 days, for which he has taken three doses of furo-
and has been doing well with ongoing optimization of his
semide. He denies significant shortness of breath but
HF regimen. The patient reports that he was admitted to the
reports he has to stop more often while walking. He can
hospital for 2 days because of decompensation with volume
As you take the posttest for this chapter, also evaluate the Use the 5-point scale to indicate whether this chapter pre-
material’s quality and usefulness, as well as the achievement pared you to accomplish the following learning objectives:
of learning objectives. Rate each item using this 5-point scale:
29. Apply treatment strategies to reduce the progression of
heart failure (HF) through assessing functional class.
• Strongly agree
30. Evaluate and justify traditional and newer treatment
• Agree strategies for patients with stage C HF, specifically as
• Neutral they relate to the 2017 guideline updates.
• Disagree 31. Develop treatment strategies for patients with stage D
• Strongly disagree HF.
32. Evaluate treatment strategies for potential benefit/harm
18. The content of the chapter met my educational needs.
for the patient with HF with preserved ejection fraction.
19. The content of the chapter satisfied my expectations.
20. The author presented the chapter content effectively.
OTHER COMMENTS
21. The content of the chapter was relevant to my practice 33. Please provide any specific comments relating to any
and presented at the appropriate depth and scope. perceptions of bias, promotion, or advertisement of
22. The content of the chapter was objective and balanced. commercial products.
23. The content of the chapter is free of bias, promotion, or 34. Please expand on any of your above responses, and/or
advertisement of commercial products. provide any additional comments regarding this chapter:
24. The content of the chapter was useful to me.
25. The teaching and learning methods used in the chapter
were effective.
26. The active learning methods used in the chapter were
effective.
27. The learning assessment activities used in the chapter
were effective.
28. The chapter was effective overall.