Outpatient Med Management in Heart Failure Materials

HEART TO HEART: OUTPATIENT MEDICATION MANAGEMENT IN HEART FAILURE

KELSEY GIARA, PharmD, RPh

Kelsey Giara is a pharmacist and freelance medical writer based in New Hampshire. She writes about a variety of healthcare topics for various publications and has significant experience in continuing medical education, needs assessments, grant writing, and medical communications.

Topic Overview

Heart failure (HF) is a complex, chronic condition with significant morbidity and mortality. Understanding the pathophysiology of HF is crucial, as it involves intricate mechanisms beyond simple heart dysfunction. Various medications are available to manage HF, and treatment must be tailored to individual patient needs through shared clinical decision-making. Patients must adhere to myriad pharmacotherapies in addition to lifestyle changes to control symptoms and prevent disease progression and worsening. Effective outpatient management of HF requires a collaborative approach to optimize treatment outcomes and improve patients' quality of life. Pharmacy teams are vital in recognizing symptoms, ensuring adherence to therapeutic regimens, and providing comprehensive patient education.

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Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist  0669-0000-24-154-H01-P

Pharmacy Technician  0669-0000-24-155-H01-T

Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $6.99

Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Course Test and course evaluation

Release Date: October 26, 2024 Expiration Date: October 26, 2027

Target Audience: This educational activity is for pharmacists and pharmacy technicians

How to Earn Credit: From October 26, 2024, through October 26, 2027, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “Educational Activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives:

Upon completion of this educational activity, participants should be able to:

Describe the pathophysiology and burden of heart failure

Discuss the latest guidelines for treating heart failure

Review medications used to treat heart failure

Demonstrate effective strategies for counseling patients with heart failure

Disclosures

The following individuals were involved in developing this activity: Kelsey Giara, PharmD, RPh, and Pamela Sardo, PharmD, BS. Pamela Sardo and Kelsey Giara have no conflicts of interest or financial relationships regarding the subject matter. There are no financial relationships or commercial or financial support relevant to this activity to report or disclose by RxCe.com or any of the individuals involved in the development of this activity.

© RxCe.com LLC 2024: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Educational Activity

Heart to Heart: Outpatient Medication Management in Heart Failure Introduction

Blood plays a central role in sustaining human life. It regulates the body through temperature control, pH and fluid balance, immune system function, and clotting mechanisms to stop bleeding. Arguably, the blood’s most important function is as a transportation system that delivers oxygen and nutrients to all the body’s cells and removes waste to maintain a balanced internal environment. Disrupting this system produces significant consequences.

As the regulator of blood pressure and circulation, the heart must function properly for blood to distribute and perform its many essential functions. Heart failure (HF) is a complex cardiovascular syndrome resulting from structural or functional impairment of the heart that causes reduced ability to fill the ventricles or eject blood.1 HF’s hallmark feature is diminished blood volume or pressure, reducing the heart’s ability to circulate blood to the body’s tissues. The most common symptoms associated with HF include dyspnea (shortness of breath), trouble breathing when lying down, weight gain with swelling in the feet, legs, ankles, or stomach (called dependent edema), and generally feeling weak or tired.2

Despite significant progress in the treatment of many forms of heart disease, HF remains a growing issue in the United States (US). About 6.2 million American adults have HF, and the condition contributes to about 13.4% of deaths in the country.3 Risk factors for HF include coronary artery disease and heart attacks, diabetes, hypertension, obesity, and other categories of cardiovascular disease (CVD).1,2 About 115 million people in the US have hypertension, 100 million have obesity, 92 million have prediabetes, 26 million have diabetes, and 125 million have atherosclerotic CVD.1 This leaves a significant portion of the population at risk of developing HF. Unhealthy behaviors can also increase a person’s risk for HF, including smoking tobacco,

eating a diet high in fat, cholesterol, and sodium, sedentary lifestyle, and excessive alcohol intake.2

Heart Failure Development and Diagnosis Heart Failure’s Effects on the Body

Under normal circumstances, blood flows through the heart in a circuitous pattern, as shown in Figure 1.4 Blood that is low on oxygen travels from the body into the heart’s right atrium through the superior and inferior vena cava. Blood then passes through the tricuspid valve to the right ventricle, which pumps it into the lungs through the pulmonary artery. In the lungs, the blood picks up oxygen and travels back into the left atrium of the heart through the pulmonary veins. This oxygen-rich blood then passes through the mitral valve to the left ventricle, which pumps the blood through the aorta to supply the rest of the body’s tissues with oxygen.4 This entire process takes about 16 seconds and circulates about 5 quarts of blood per minute.5

Figure 1

Blood Flow Through the Heart4

A central component of HF pathophysiology is changes to the renin- angiotensin-aldosterone system (RAAS).6 The RAAS system consists of hormones, proteins, enzymes, and reactions to regulate blood pressure and volume.7 Three major substances work together to increase sodium reabsorption, water reabsorption, and vascular tone (the extent to which blood vessels constrict): renin (an enzyme), angiotensin II (a hormone), and aldosterone (a hormone). The RAAS system also involves various organs and body systems, including the kidneys, liver, blood vessels, lungs, adrenal and pituitary glands, and the hypothalamus (a region of the brain).

The RAAS system involves many steps, including the following:7

A drop in blood pressure triggers the kidneys to release renin into the bloodstream

The enzyme renin breaks down angiotensinogen (a protein produced by the liver) to produce angiotensin I (an inactive hormone)

Angiotensin-converting enzyme (ACE) in the lungs and kidneys breaks down angiotensin I to produce angiotensin II (an active hormone)

Angiotensin II causes the muscular walls of small arteries to constrict to increase blood pressure; it also causes adrenal glands to release aldosterone and the pituitary gland to release antidiuretic hormone (ADH, or vasopressin)

Aldosterone and ADH cause the kidneys to retain sodium; aldosterone also causes the kidneys to excrete potassium through the urine

Increased sodium in the bloodstream causes water retention, thus increasing blood volume and blood pressure

Early in the development of HF, the RAAS system adapts in response to the body’s inability to meet the demands of vital organ systems.6,7 Specifically, as the body recognizes a lack of blood flow, the RAAS releases more angiotensin II, which subsequently exacerbates HF progression and symptoms through sodium and water retention, cardiac remodeling (changes in the size,

shape, structure, and function of the heart), oxidative stress, sympathetic nervous system (SNS) activation, ADH secretion, and vasoconstriction.

The SNS also contributes to HF’s pathophysiology through complex hormonal interactions closely connected with the RAAS.6 Initially, increased catecholamines (stress hormones) can temporarily boost heart function, stimulating stronger and faster heartbeats. However, over time, this can lead to worsened blood flow to the heart, thickening of the heart muscle, and irregular heart rhythms. In response, the body produces natriuretic peptides, such as A-type and B-type natriuretic peptides (BNP), which help counteract the effects of the RAAS and SNS by causing blood vessels to widen and the body to excrete more salt, further reducing the influence of the SNS and RAAS. An enzyme called neprilysin breaks down these peptides and has emerged as a new target in HF treatment. In short, while the RAAS and SNS initially help improve heart function, their prolonged effects eventually overpower the body's protective mechanisms, leading to HF progression.6

Classifying Heart Failure

American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) guidelines classify HF based on ejection fraction measurements and symptoms.1 These classifications guide treatment decisions. Left ventricular ejection fraction (LVEF) measures how much blood the left ventricle ejects back into the body with each contraction (heartbeat) relative to its filled volume. For example, if the left ventricle fills with 100 mL of blood and pumps out 60 mL with each heartbeat, the ejection fraction would be 60%. Four major types of HF exist based on a patient’s ejection fraction:1

HF with reduced ejection fraction (HFrEF): LVEF 40% or less; characterized by a weakened heart muscle that does not contract effectively

HF with improved ejection fraction (HFimpEF): previous LVEF of 40% or less and a follow-up measurement of LVEF greater than 40%;

patients remain at risk for HF symptoms or events and need continued treatment and monitoring

HF with mildly reduced ejection fraction (HFmrEF): LVEF between 41% and 49% with evidence of spontaneous or provokable increased left ventricular filling pressures

HF with preserved ejection fraction (HFpEF): LVEF 50% or greater; involves heart muscle being unable to relax normally and fill effectively

ACC/AHA/HFSA guidelines also classify patients with HF based on four stages of disease:1,8

Stage A: at risk of HF but without current or previous signs and symptoms and without structural/functional heart disease or abnormal biomarkers; includes patients with hypertension, cardiovascular disease (CVD), diabetes, obesity, exposure to cardiotoxic agents (e.g., cancer treatments, cocaine, methamphetamine), family history of cardiomyopathy, or genetic variant for cardiomyopathy

Stage B: without current or previous signs and symptoms but evidence of one of the following:

Structural heart disease

Evidence of increased filling pressures

HF risk factors and with increased natriuretic peptide levels or persistently elevated cardiac troponin (in the absence of competing diagnoses)

Stage C: current or previous signs and symptoms of HF

Stage D: marked HF symptoms that interfere with daily life and lead to recurrent hospitalizations despite guideline-directed medical therapy

Patients with stage C disease are further categorized based on their symptom trajectory as either new onset (de novo) HF, resolution of symptoms, persistent HF, or worsening HF.1 Importantly, patients who are initially diagnosed as symptomatic (stage C) may become asymptomatic with treatment, but they maintain their status as stage C HF. Additionally, if patients experience full resolution of all symptoms, signs, and structural abnormalities, they are considered to have HF in remission.1

To characterize symptoms and functional capacity of patients with stage C or D HF, ACC/AHA/HFSA guidelines also use the New York Heart Association (NYHA) classification.1 NYHA functional classification is an independent predictor of mortality, and physicians use this classification to determine patients’ eligibility for certain treatments and to measure patients’ response to treatment.1,8 Patients with Class I disease have no physical activity limitations and no undue fatigue, palpitation, or shortness of breath with ordinary physical activity. Class II describes patients who are comfortable at rest but experience slight physical activity limitations with ordinary physical activity, resulting in fatigue, palpitation, shortness of breath, or chest pain. Patients in NYHA Class III are comfortable at rest but have marked physical activity limitations, as less than ordinary activity causes the symptoms above. Class IV is the most severe, with patients experiencing HF symptoms at rest and further discomfort with any level of physical activity.8

Treating Heart Failure: A Stage-based Approach

Guideline-directed treatment of HF is essential for optimizing patient outcomes and enhancing quality of life. ACC/AHA/HFSA guidelines outline HF treatment based on the stage of the disease, with evidence-based recommendations for managing the disease across various stages and types, focusing on pharmacologic interventions, lifestyle changes, and advanced therapeutic options.

Stage A: Primary Prevention

Guidelines recommend primary prevention strategies for all patients at risk of HF (stage A). Various healthy lifestyle habits have been associated with a lower lifetime risk of developing HF, including regular physical activity, maintaining normal weight, blood pressure, and blood glucose levels, healthy dietary patterns, and smoking cessation. The following interventions are recommended for primary prevention of HF in patients with stage A disease:1

Patients with hypertension and a CVD risk of 10% or greater should be treated to a blood pressure goal of less than 130/80 mmHg

Patients with type 2 diabetes (T2D) and either established CVD or at high cardiovascular risk should take a sodium-glucose cotransporter 2 (SGLT2) inhibitor to prevent HF-related hospitalization

All patients should adhere to healthy lifestyle habits to avoid obesity, such as regular physical activity and healthful eating habits (i.e., those based on increased consumption of plant-derived foods, such as the Mediterranean diet and the Dietary Approaches to Stop Hypertension [DASH] diet)

Patients with established CVD should continue with optimal, guideline-directed CVD management

Patients with exposure to cardiotoxic agents (e.g., chemotherapy, cocaine, methamphetamine) should undergo multidisciplinary evaluation for management of this risk

Patients with other risk factors, including genetic or inherited cardiomyopathies, should undergo genetic screening and counseling, natriuretic peptide biomarker screening, and other risk evaluations

Stage B: Preventing Symptomatic HF

Stage B represents a group of patients with structural and functional cardiac abnormalities increasing the risk of HF but without existing symptoms of the disease.1 Beginning HF treatment during stage B is an opportunity to prevent or delay the transition to symptomatic disease (stage C or D). In addition to recommended interventions for this class, all patients with stage

B disease should continue any lifestyle modifications and management strategies recommended and/or implemented in stage A.1

Pharmacologic therapy is recommended for patients with stage B HFrEF (LVEF 40% or less) to prevent symptomatic HF.1 All patients with HFrEF should take an angiotensin-converting enzyme (ACE) inhibitor, and patients who are intolerant to ACE inhibitors should use an angiotensin receptor blocker (ARB) if they have a recent history of myocardial infarction (MI). In addition to preventing symptomatic HF, ACE inhibitors and ARBs reduce the risk of mortality.

Patients with HFrEF and a history of MI or acute coronary syndrome (ACS) should initiate statin therapy and a beta-blocker.1 Statins inhibit the enzyme HMG-CoA reductase to decrease the levels of “bad” cholesterol, decreasing plaque in the arteries. This leads to a decreased incidence of myocardial infarction and decreased subclinical ischemia (i.e., improved blood flow), decreasing cardiac damage and, subsequently, the risk of HF.9 In addition to preventing symptomatic HF, statin therapy also prevents adverse cardiovascular events in this patient population, and beta-blockers reduce mortality.

Evidence for beta-blocker use in patients with stage B HFrEF to prevent symptomatic disease is limited, but guidelines recommend that providers consider using them in this subset of patients as well.1 Patients with stage B HFrEF should avoid certain drugs due to increased risk of harm, including thiazolidinediones (e.g., pioglitazone, rosiglitazone) and some non- dihydropyridine calcium channel blockers (e.g., diltiazem, verapamil).1

Stage C and D: Non-Pharmacologic and Pharmacologic Interventions

Experts make various recommendations regarding non-pharmacologic interventions for stage C HF to be implemented in conjunction with those described for stages A and B. Most importantly, patients with symptomatic HF should be treated by a multidisciplinary team to facilitate guideline-directed care, address potential barriers to self-care, reduce the risk of re-

hospitalization for HF, and improve survival.1 This team should include cardiologists, nurses, pharmacists specializing in HF, dieticians, mental health professionals, social workers, primary care clinicians, and other applicable specialists.

Other recommendations include vaccination against respiratory illnesses to reduce related mortality and screening for depression, social isolation, frailty, and low health literacy as risk factors for poor self-care. Motivation and ability for self-care are critical for patients with HF, as a great deal is expected from them, including treatment adherence and health maintenance behaviors. Patients must take medications as prescribed, restrict sodium intake, stay physically active, understand how to monitor for signs and symptoms of worsening HF, and have a plan for what to do in response to symptoms when they do arise.

Upon establishing a diagnosis, providers should address congestion (fluid retention/edema) and initiate guideline-directed medical therapy. Patients with fluid retention should take a loop diuretic (e.g., bumetanide, furosemide, torsemide) to relieve congestion, improve symptoms, and prevent disease worsening.1 Patients with hypertension and only mild fluid retention could alternatively use a thiazide diuretic, such as chlorthalidone or hydrochlorothiazide. Patients whose edema does not resolve with loop diuretics alone may benefit from the addition of metolazone or chlorothiazide.1

Guideline-directed medical therapy for stage C HFrEF includes a RAAS- acting agent, a beta blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor.1 RAAS inhibitor selection depends upon a patient’s NYHA functional classification; an angiotensin receptor-neprilysin inhibitor (ARNi) is recommended for NYHA class II-III, and an ACE inhibitor or ARB is recommended for NYHA class II-IV. Providers should titrate to target dosing as tolerated and based on laboratory values, health status, and LVEF.

Patients who move to HFimpEF with an LVEF greater than 40% should continue the guideline-directed medical therapy described above. For patients who fail to improve (persistent stage C HFrEF with LVEF 40% or less), providers should consider the following situations:1

NYHA III-IV in African American patients: add hydral-nitrates (i.e., hydralazine and isosorbide dinitrate)

NYHA I-III with LVEF 35% or less and greater than 1 year of survival: consider an implantable cardioverter-defibrillator (ICD)

NYHA II-III or ambulatory IV with LVEF 35% or less and certain heartbeat abnormalities: consider cardiac resynchronization therapy

A subset of patients remains refractory (or move to stage D disease) despite these measures. They continue to progress and develop severe, persistent HF symptoms even with maximized guideline-directed medical therapy. These patients require prompt referral for specialty HF care where providers will consider advanced HF therapies (e.g., LVAD, heart transplant, palliative care measures).1

Pharmacotherapy for Heart Failure

Pharmacotherapy plays a pivotal role in the management of HF. The various medication classes discussed target differing HF mechanisms and manifestations, working together to improve symptoms, enhance quality of life, prevent hospitalization, and extend survival. Table 1 lists recommended dosing of the most common pharmacotherapy used to treat HF.

Table 1

Adult Dosing of Heart Failure Pharmacotherapy*1,10-14

*All drugs listed are administered orally; see full prescribing information for pediatric dosing as applicable. ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor-neprilysin inhibitor; BID, twice daily; CrCl, creatinine clearance (in mL/min); ER, extended-release; QOD, every other day; SGLT2, sodium-glucose cotransporter 2; TID, three times daily.

RAAS-Acting Agents

Altering the RAAS system with an ARNi, ACE inhibitor, or ARB is recommended to reduce morbidity and mortality for patients with HFrEF.1 An ARNi is the preferred agent whenever feasible and tolerated, followed by an ACE inhibitor, then an ARB. As described, HF develops due to an imbalance between the RAAS system and the body’s protective mechanisms (i.e., secretion of natriuretic peptides).6 Different drug classes affect different steps in this process, as shown in Figure 2. Patients should start all RAAS-acting drugs at the lowest dose and titrate up slowly, increasing the dose every 2 weeks at the fastest. Importantly, if patients switch between RAAS-acting agents in differing classes, they should allow at least 36 hours between discontinuing one and starting another.1

Figure 2

Effects of Pharmacotherapy on the Renin-Angiotensin-Aldosterone System1,6

ACE, angiotensin-converting enzyme; ACE-i, ACE inhibitors; ARBs, angiotensin receptor blockers; ARNI, angiotensin receptor-neprilysin inhibitor; BBs, beta-blockers; MRAs, mineralocorticoid receptor antagonist.

As the name suggests, ACE inhibitors block ACE to prevent the synthesis of angiotensin II.15 Data show that available ACE inhibitors do not differ based on their efficacy for symptoms or survival.1 Major adverse effects associated with ACE inhibitors include cough, hypotension, dyspnea, dizziness, headache, and gastrointestinal (GI) symptoms.15 ACE inhibitors can also produce angioedema, a serious condition where swelling occurs in the deeper layers of the skin and the mouth and throat lining.16 This can become life-threatening if the swelling affects the larynx. ACE inhibitors are a leading cause of angioedema; this medication class causes 20% to 40% of all emergency department visits for angioedema.16 Pharmacists must make patients aware of this potential adverse effect and the need to seek immediate medical attention. Contraindications to ACE inhibitor use include a history of ACE inhibitor-associated angioedema and concomitant use with aliskiren.11

ARBs directly block the effects of angiotensin II at its receptor. While not the preferred RAAS inhibitor for patients with HF, some still use these medications to treat the disease, given their ability to reduce mortality and

HF-related hospitalizations.1 ARBs are associated with a lower incidence of cough and angioedema compared to ACE inhibitors, making them beneficial for patients who develop these adverse reactions to ACE inhibitors.

Angiotensin receptor-neprilysin inhibitors—a newer drug class for HF treatment—combine an ARB (valsartan) and a neprilysin inhibitor (sacubitril).1,10 Neprilysin is the enzyme that degrades natriuretic peptides, bradykinin, adrenomedullin, and other vasoactive peptides. Inhibiting the breakdown of these substances helps to counteract RAAS overactivation and promote sodium and water excretion, thus reducing fluid overload in patients with HF. Sacubitril-valsartan is effective for HF due to the synergistic effects of RAAS inhibition and increasing the levels of beneficial substances (i.e., natriuretic peptides). In clinical trials, sacubitril-valsartan was superior to enalapril (an ACE inhibitor), reducing the risk of cardiovascular death or HF hospitalization by 20% compared to enalapril.1 The drug is FDA-approved for adults and children aged one year and older and comes in a “sprinkle” formulation for administration to pediatric patients or adults unable to swallow tablets. Patients take sacubitril-valsartan twice daily without regard to food.10

Sacubitril-valsartan is contraindicated in patients with a history of angioedema to previous ACE inhibitor or ARB therapy.10 The drug is also contraindicated with concomitant ACE inhibitor use and with concomitant aliskiren use in patients with diabetes. Patients who are not currently taking an ACE inhibitor or ARB, are taking a low dose of one of these agents, or who have severe renal impairment or moderate hepatic impairment should reduce to half the recommended initial starting dose. Adverse effects associated with sacubitril-valsartan (occurring in at least 5% of patients) include hypotension (low blood pressure), hyperkalemia (elevated potassium), cough, dizziness, and kidney failure. The drug also carries a boxed warning for fetal toxicity. Drug-drug interactions for sacubitril-valsartan include potassium-sparing diuretics (risk of hyperkalemia), nonsteroidal anti-inflammatory drugs (may increase risk of kidney impairment), and lithium (increased risk of lithium toxicity).10

Beta Blockers

Three beta blockers are proven to reduce the risk of death and the combined risk of death or hospitalization in patients with HFrEF: bisoprolol, carvedilol, and sustained-release metoprolol succinate.1,11 All of these agents block the beta-1 adrenergic receptor located on the surface of the heart, and carvedilol additionally targets beta-2 and alpha-1 receptors, leading to vasodilation.

Patients should initiate beta blockers at a low dose and slowly titrate to the target maintenance dose as tolerated.11 Fluid retention and worsening HFrEF, fatigue, bradycardia, heart block, and hypotension can occur. However, these issues—particularly fluid retention or worsening HFrEF—typically do not require permanent discontinuation. Beta-blocker-induced bradycardia often does not cause symptoms and may not need intervention, but if it causes dizziness, lightheadedness, or severe heart block, dose reduction is necessary. Providers should closely monitor patients for any changes in vital signs and symptoms during dose adjustments. Patients who cannot tolerate the target doses should continue therapy at the highest tolerated dose.11

Mineralocorticoid Receptor Antagonists

MRAs are recommended for patients with NYHA class II-IV HFrEF, a glomerular filtration rate of at least 30 mL/min/1.73 m2, and a potassium level of 5.0 mEq/dL or less.1,11 Available FDA-approved MRAs—spironolactone and eplerenone—show consistent improvements in all-cause mortality, HF- related hospitalizations, and sudden cardiac death in patients with HF. These drugs inhibit aldosterone, an endogenous steroid hormone that increases sodium retention and facilitates magnesium and potassium excretion. Aldosterone contributes to HFrEF development by causing myocardial fibrosis, vascular injury, direct vascular damage, and baroreceptor dysfunction, so blocking it with MRAs may slow HF progression.

Spironolactone is a nonselective aldosterone antagonist, while eplerenone is selective for the aldosterone receptor.1,11 While little data exists directly comparing these two drugs, patients often tolerate eplerenone better

due to its higher selectivity and less propensity to cause adverse effects such as gynecomastia (breast tissue enlargement in men and boys) and vaginal bleeding.1 Patients who develop diarrhea causing dehydration or loop diuretic therapy interruption because of worsening renal function or hyperkalemia should temporarily hold MRA therapy. They should also discontinue MRA therapy indefinitely if they cannot maintain a serum potassium level of 5.5 mEq/dL or less to avoid life-threatening hyperkalemia, so close monitoring of potassium levels is vital.1

SGLT2 Inhibitors

Initially, researchers developed SGLT2 inhibitors for patients with diabetes.17 These drugs inhibit SGLT2 in the proximal tubule of the kidney to lower blood glucose levels. Studies went on to establish whether these drugs were safe for use in patients with cardiovascular conditions and risk factors for CVD. Results found unexpected beneficial effects on the rates of major adverse cardiovascular events (MACE)—including cardiovascular events, cardiovascular death, and all-cause mortality—in patients with atherosclerotic CVD. This reduction in MACE was primarily driven by the prevention of HF- related hospitalization, leading researchers to evaluate the utility of these drugs for patients with HF who were not diabetic.17

Research shows that patients with T2D and either established CVD or high risk for CVD who take an SGLT2 inhibitor have a lower risk for HF hospitalization compared to placebo.1 Guidelines recommend that patients with symptomatic chronic HFrEF, regardless of the presence or absence of T2D, take an SGLT2 inhibitor to reduce the risk of HF hospitalization and cardiovascular mortality. Importantly, this will not lead to hypoglycemia in patients without T2D. Three SGLT2 inhibitors are currently FDA-approved for use in HF: dapagliflozin, empagliflozin, and sotagliflozin.12-14

Dapagliflozin is FDA-approved to reduce the risk of cardiovascular death, HF hospitalization, and urgent HF visits in adults with heart failure.12 The drug is also indicated to reduce the risk of disease worsening, cardiovascular death, and hospitalization in adults with chronic kidney disease (CKD) at risk of

progression; to reduce the risk of HF hospitalization in adults with T2D and either established CVD or multiple cardiovascular risk factors; and as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged ten years and older with T2D. Patients take dapagliflozin in the morning with or without food. The drug’s most common adverse effects (occurring in at least 5% of patients) are female genital mycotic infections, nasopharyngitis, and urinary tract infections.12 Dapagliflozin also carries warnings for ketoacidosis (acid buildup in the blood), volume depletion, and hypoglycemia.

Empagliflozin is FDA-approved to reduce the risk of cardiovascular death and HF hospitalization in adults with heart failure.13 The drug is also indicated to reduce the risk of disease worsening, cardiovascular death, and hospitalization in adults with CKD at risk of progression; to reduce the risk of cardiovascular death in adults with T2D and established CVD; and as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged ten years and older with T2D. Patients using empagliflozin should take the drug in the morning with or without food. Empagliflozin’s most common adverse effects (occurring in at least 5% of patients) are urinary tract infections and female genital mycotic infections. The drug also carries warnings for ketoacidosis, volume depletion, hypoglycemia, lower limb amputation, and serious hypersensitivity reactions.13

Sotagliflozin, the newest SGLT2 inhibitor, is approved to reduce the risk of cardiovascular death, HF hospitalization, and urgent HF visits in adults with heart failure, as well as patients with type 2 diabetes, CKD, or other cardiovascular risk factors.14 Patients take sotagliflozin in the morning, not more than one hour before the first meal of the day, and should swallow the tablet whole. They should also wait two weeks before titrating up to the maintenance dose of 400 mg daily. If patients miss a dose of sotagliflozin by more than 6 hours, they should skip that dose entirely and resume therapy as prescribed the following day. Sotagliflozin’s most common adverse effects (occurring in at least 5% of patients) are urinary tract infection, volume depletion, diarrhea, and hypoglycemia. The drug also increases the risk of ketoacidosis and various bacterial and mycotic infections.14

Patients should withhold SGLT2 inhibitor use for three days prior to major surgery or procedures associated with extended periods of fasting and resume when clinically stable and back to typical oral intake.12-14

Diuretics

Diuretics are not shown to reduce mortality or hospitalization rates for patients with HF, but they are the only agents that can adequately control fluid retention in patients with HFrEF.11 All patients with fluid retention should use diuretics to improve symptoms unless otherwise contraindicated.

Two types of diuretics are used in HF: loop diuretics and thiazide (or thiazide-like) diuretics.1,11 Loop diuretics—bumetanide, ethacrynic acid, furosemide, and torsemide—work in the Loop of Henle in the nephrons of the kidneys to inhibit sodium and chloride reabsorption. Thiazide diuretics— chlorthalidone, hydrochlorothiazide, and metolazone—work at the distal convoluted tubule of the kidney to inhibit the sodium chloride cotransporter. Loop diuretics are preferred for most patients with HFrEF, as they are more potent than thiazides and have a more significant effect on fluid retention and edema. For some, maximal loop diuretic therapy is not sufficient to resolve volume overload. These patients may require intravenous loop diuretics or the addition of chlorthalidone or metolazone.1,11 Other patients who benefit from thiazides include those with concurrent hypertension and mild fluid retention; for these individuals, prescribers should consider chlorthalidone or hydrochlorothiazide.1,11

Common adverse effects of diuretics include fluid depletion, hypotension, azotemia (high levels of nitrogen-containing compounds in the blood), and depletion of sodium, potassium, magnesium, chloride, and calcium.11 Patients using these agents must monitor their weight and blood pressure daily. They should also undergo periodic renal function and uric acid monitoring. Despite recommended maintenance doses, diuretic therapy is best initiated at low doses and titrated slowly based on patient response. Optimal dosing is determined by increased urine output and a decrease in daily weight from 0.5 kg to 1.0 kg.11

Vasodilators

Evidence shows that vasodilators—hydralazine and isosorbide dinitrate—improve outcomes in some patients with HF:1,11

reduced mortality in patients self-described as African American with NYHA class III-IV HFrEF who remain symptomatic despite concomitant use of an ACE inhibitor/ARB, a beta blocker, and an MRA

reduced morbidity and mortality in patients with current or prior symptomatic HFrEF who cannot take an ACE inhibitor or ARB because of drug intolerance, hypotension, or renal insufficiency

Hydralazine selectively relaxes the smooth muscle in the arteries, while isosorbide dinitrate causes a release of nitric oxide that relaxes the vascular smooth muscle in both arteries and veins.11 Both of these mechanisms produce vasodilatory effects. Studies show that African American patients who use these vasodilators experience a 43% reduction in relative risk of death and a 33% reduction in the risk of first HF hospitalization.11 Evidence suggests that vasodilators’ selective utility in African American patients is due to this population’s increased incidence of hypertension and decreased levels of plasma norepinephrine and renin.

Hydralazine and isosorbide dinitrate can be administered separately or in a combination tablet.11 Combination tablets reduce patients’ pill burden, which could improve adherence. Patients who tolerate the starting dose for two weeks without major adverse effects can double the dose for maintenance therapy. Adverse effects of hydralazine and isosorbide dinitrate include nausea, fatigue, palpitations, joint pain, and rash.11 Patients should never use phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil) in combination with isosorbide dinitrate due to an increased risk of dangerously low blood pressure that could be fatal.

Other Therapies

After optimizing other guideline-directed medication therapies, clinicians can consider additional medical therapies on a patient-specific basis for the following scenarios.

Symptomatic HFrEF: Digoxin—a cardiac glycoside—has been shown to decrease the rate of HF-associated hospitalizations when used in addition to standard of care.11 In patients with HF, digoxin slows the heart rate down and improves the ventricles’ ability to fill with blood. Despite being used for this indication extensively, this drug’s role and utility in chronic HF are still controversial due to its narrow therapeutic index and increased risk of adverse effects.1,11 Common adverse effects of digoxin, which are generally dose- dependent (increased doses lead to increased adverse effects), include central nervous system effects (e.g., visual changes, anxiety, dizziness) or gastrointestinal effects (e.g., anorexia, nausea, vomiting, abdominal pain). Cardiac toxicity is also possible.11 These effects are less common when patients are treated within the therapeutic dose range, and serum concentrations of the drug remain between 0.5 to less than 0.9 ng/mL.1,11

NYHA Class II–III HFrEF with normal sinus rhythm: Ivabradine is an I(f) channel (“funny current”) inhibitor used to reduce the heart rate in patients with HFrEF.11 The I(f) channel controls the heart rate by modulating neurotransmitters like epinephrine. Inhibiting this channel slows the heart rate. Ivabradine is indicated in patients with stable, symptomatic, chronic HF with an LVEF of 35% or less and a resting heart rate greater than 70 beats per minute (bpm).11 However, given the proven benefits of beta-blocker therapy in HF, patients should initiate and titrate beta blockers to maximally tolerated doses before adding ivabradine.1 Clinicians should adjust ivabradine doses based on heart rate two weeks after therapy initiation.11,18 The target heart rate for patients taking this drug is 50 to 60 bpm. Common adverse effects of ivabradine include bradycardia (slower than normal heart rate), hypertension, atrial fibrillation (irregular/rapid heart rhythm), and luminous phenomena (“seeing stars” or “fuzzy” vision changes).18 Ivabradine also has many contraindications, including the following:

acute decompensated heart failure

clinically significant hypotension

sick sinus syndrome, sinoatrial block, or 3rd-degree AV block, unless a functioning demand pacemaker is present

clinically significant bradycardia

severe hepatic impairment

pacemaker dependence (heart rate maintained exclusively by the pacemaker)

concomitant use of strong cytochrome P450 (CYP) 3A4 inhibitors, including azole antifungals (e.g., itraconazole), macrolide antibiotics (e.g., clarithromycin, telithromycin), protease inhibitors (e.g., nelfinavir), and nefazodone

NHYA Class II-IV with LVEF less than 45%, recent HF hospitalization or intravenous diuretics, and elevated natriuretic peptide levels: Vericiguat is an oral soluble guanylyl cyclase (sGC) stimulator that directly binds to and stimulates sGC to increase cyclic guanosine monophosphate (cGMP) production.1,19 cGMP has several potentially beneficial effects in patients with HF, including vasodilation, improved endothelial function, and decreased fibrosis and heart remodeling. In select high-risk patients with HFrEF and recent worsening of HF despite guideline-directed medical therapy, vericiguat has been shown to reduce the risk of HF hospitalization and cardiovascular death.1 Patients should take vericiguat with food. If a patient cannot swallow the tablets, vericiguat tablets can be crushed and mixed with water immediately before being administered.19 Concomitant use of vericiguat with PDE-5 inhibitors is not recommended due to increased risk of serious hypotension.

NYHA Class II-IV: HF guidelines suggest that omega-3 polyunsaturated fatty acid (PUFA) supplementation may be a reasonable adjunctive therapy to reduce mortality and cardiovascular hospitalizations.1 Clinical trial data shows that PUFA supplementation can reduce the risk of fatal and nonfatal cardiovascular events by up to 20% when used alongside other evidence- based therapies. Guidelines do not suggest a specific dose of this therapy, but

1 gram daily of omega-3 PUFA has been shown to be effective and well tolerated in clinical trials.1

Patients with hyperkalemia while taking RAAS inhibiting therapy: Hyperkalemia (serum potassium level 5.5 mEq/L or greater) is common in HF and can lead to arrhythmias and underuse of RAAS inhibiting therapies. Potassium binders—including patiromer or sodium zirconium cyclosilicate (SZC)—may be helpful in patients with HF who experience hyperkalemia while taking a RAAS inhibitor.1 Clinical trials show that these agents reduce potassium levels, but whether patiromer or SZC improves clinical outcomes in patients with HF is still under investigation. Adverse effects of potassium binders include hypomagnesemia (for patiromer) and edema (for SZC).1

Improving Care for Patients with Heart Failure

Pharmacists and pharmacy technicians play crucial roles in the comprehensive management of HF, ensuring that patients receive optimal care and support. Pharmacists are responsible for providing clinical expertise, managing medication therapy, and counseling patients on proper medication use, while pharmacy technicians assist with medication dispensing and serve as the main point of contact for patients with HF visiting the pharmacy. Together, they form an integral part of the healthcare team, working collaboratively to improve patient outcomes and quality of life for those with heart failure.

Improving Patient Self-Care

Patient self-care is critical to outpatient HF management and essential to minimizing disease impacts and progression.20 This includes a range of behaviors, including medication adherence, symptom recognition, lifestyle factors (e.g., daily weighing, exercise, smoking cessation, healthy diet), and the ability to seek prompt medical attention when appropriate. Failure to adhere to healthcare providers’ instructions for self-care is a common cause of HF exacerbation and subsequent hospital readmission.21 Pharmacists should assess patients’ existing routines and lifestyle habits to individualize recommendations and integrate new behaviors for self-care maintenance.

Patients with HF have notoriously poor self-efficacy and self-care habits, especially those with multiple comorbidities.20 Research shows that pharmacist involvement improves care and outcomes for patients with HF, including reduction of all-cause and HF-related hospitalizations, appropriate medication prescribing and evidence-based medication use, reduction of medication discrepancies and prescription errors, and reduction of clinically relevant drug-drug interactions.20

Optimizing Transitions of Care

Pharmacists can aid in transitioning patients from hospital to home to ensure the continuation of optimal care. Pharmacists should be directly involved in medication reconciliation as part of the transitional care team, as many studies show medication reconciliation decreases 30-day hospital readmission rates for patients with HF.20

The American College of Clinical Pharmacy’s Cardiology Practice and Research Network developed best practices for discharge counseling following hospitalization for HF.21 Following hospital admission for an acute decompensated HF episode or frequent hospitalizations for HF, patients should receive frequent and comprehensive education. Pharmacists should tailor counseling to the patient's baseline knowledge and whether the admission is their first or a recurrent cardiac event. Counseling should start upon hospital admission and continue daily throughout the stay—typically at least 2 to 3 days long for HF admissions—to reinforce and add new information. The duration of each counseling session depends on the patient's and caregivers' understanding levels. It is crucial to introduce core concepts during the initial admission to establish a foundation for adherence and self-care, acknowledging that patients may not retain all information in one visit.

Upon returning to their community pharmacies, patients with HF still need ongoing pharmacist involvement in care to reinforce core concepts and facilitate ongoing education. Studies show that patients welcome the opportunity for open discussion with a community pharmacist to supplement the care and information they receive from prescribing clinicians.20

Additionally, data shows that patients generally have an increased understanding of HF and its treatment following participation in pharmacist- led counseling.

The major principles of counseling in any care setting for HF should include the following:21

Addressing    existing  barriers: Educational sessions should be individualized, beginning with an assessment of the patient's clinical status, baseline knowledge, and specific learning needs to tailor the approach accordingly. Identifying and addressing barriers to learning, such as low literacy, financial hardship, depression, and language barriers, are crucial for optimizing disease management and treatment adherence.

Assessing readiness to learn: Effective education requires assessing a patient’s readiness to learn, considering their physical, psychological, cultural, social, and financial status, and adjusting educational efforts accordingly. Comorbidities such as hyperlipidemia, diabetes mellitus, atrial fibrillation, sleep apnea, cognitive impairment, and depression must be routinely screened and managed, as they can significantly impact a patient's ability to process and retain new information.

Thorough medication review: Ample time should be dedicated to reviewing HF medications in detail with patients and caregivers, addressing medication names, doses, schedules, storage, and actions for missed doses. It is essential to explain the medication's role in the disease process, anticipated benefits, potential adverse effects, and drug interactions and to assess literacy and adherence through patient demonstrations and medication list reviews.

Using variable teaching methods: Various teaching methods, such as videos, group discussions, and written materials, can improve HF education. Patients benefit significantly from education delivered through multiple formats, and motivational interviewing can enhance their readiness to learn by addressing ambivalence and promoting commitment to change.

Supplementing verbal education with appropriate written materials and using the "teach back" method to confirm understanding ensures that patients grasp key concepts.

Caregiver  and  care  team  engagement: Involving caregivers in the educational process for patients with HF, especially those with cognitive impairment or depression, ensures better understanding and adherence to recommendations. Additionally, a multidisciplinary approach involving various healthcare professionals and utilizing group sessions provides comprehensive education and support.

Emphasizing self-care: Emphasizing the importance of self-care in HF education is crucial, as it involves patients actively managing their disease with support from caregivers. This includes making healthy lifestyle choices, recognizing signs of disease progression, and practicing necessary skills such as reading food labels and tracking medication use.

Assessing patient resources: Medication adherence is heavily influenced by patients’ access to medication resources, with drug costs being a significant barrier. Increased medication costs lead to decreased adherence, especially among lower economic subgroups. To enhance adherence, it is crucial to identify cost-saving initiatives, such as patient assistance programs and fixed generic drug copays, alongside cognitive counseling to emphasize the importance of disease-altering therapies.

Identifying Medications that May Exacerbate HF

An important role for pharmacists and technicians is to identify medications that may exacerbate HF. Non-steroidal anti-inflammatory drugs (NSAIDs; e.g., celecoxib, diclofenac, ibuprofen, indomethacin, meloxicam, naproxen) inhibit prostaglandins, which leads to sodium and water retention, increased systemic vascular resistance, and blunted response to diuretics.1 It is especially important that pharmacy teams stress this point to patients, as many NSAIDs are available over the counter. Thiazolidinediones—including pioglitazone and rosiglitazone—can worsen HF symptoms through possible calcium channel blockade.1

Some drugs are considered negative inotropes, meaning they decrease the force or strength of heart muscle contractions, which can be detrimental for patients with HF. Examples include flecainide, dronedarone, diltiazem, verapamil, and nifedipine.1 Another important medication to avoid is sotalol, a beta-blocker. This can be confusing, as beta blockers are recommended for HF treatment, but sotalol has proarrhythmic properties (i.e., it can cause or exacerbate abnormal heart rhythms) that can worsen HF. Alogliptin and saxagliptin—dipeptidyl peptidase-4 inhibitors used to treat diabetes—can also exacerbate HF through unknown mechanisms.1

Summary

Effective outpatient management of HF requires collaboration across the healthcare team. As part of the team, pharmacy staff plays a critical role. Patients visit the pharmacy more often than they see other clinicians, providing ample opportunities to optimize medication therapy for HF and provide comprehensive education to promote adherence to prescribed therapies and lifestyle changes. Optimal, guideline-directed, evidence-based care for patients with HF is vital to improve outcomes and quality of life for patients with this debilitating disease.

Course Test

What happens in the human body when it senses a lack of blood flow?

The RAAS releases more angiotensinogen

The RAAS releases more angiotensin II

The RAAS restricts the release of renin

The RAAS causes urinary calcium increases

When blood volume diminishes, patients may experience

dyspnea (shortness of breath).

trouble breathing only when standing.

equally distributed weight gain.

a general feeling of jittery energy.

A patient says he has hypertension and is newly diagnosed with HF. He says, “Thank goodness, the doctor says my heart doesn’t have structure or function changes or abnormal biomarkers.” What stage of HF is he in?

a. A

b. B

c. C

d. D

A patient has been treated for several years and looks like he is struggling for air when he picks up his prescriptions. When you ask him how he is, he says, “Eh, not so good. I have been in the hospital three times in the last three months, and I can’t breathe very well when walking or getting dressed. I should have ridden one of those motorized shopping carts when I came in.” What stage of HF is he in?

a. A

b. B

c. C

d. D

Which drug is paired correctly with its mechanism of action in HF?

Lisinopril inhibits the breakdown of natriuretic peptides and promotes sodium and water excretion

Carvedilol blocks ACE to prevent the synthesis of angiotensin II

Dapagliflozin directly blocks the effects of angiotensin II at its receptor

Spironolactone decreases sodium retention and facilitates magnesium and potassium excretion

Which medication is indicated as add-on therapy in a patient who has maximal loop diuretic therapy that is not sufficient to resolve volume overload?

Budesonide

Chlorpromazine

Metolazone

Temazepam

Alan is a 76-year-old male who has stage 3 HF. He presents at the pharmacy to pick up refills of six drugs indicated in guideline- directed care, including a diuretic, an ARB, a beta blocker, digoxin, an MRA, and a vasodilator. As he presents his insurance card, he asks if the pharmacist can recommend something for diarrhea because it’s been frequent, and he is constantly thirsty. Which medication might be a red flag leading you to ask more questions?

The ARB

The beta blocker

The digoxin

The MRA

Richard is an 83-year-old male who has had HF for 15 years. His prescriptions are on auto refill, and every 90 days, the system calls and reminds him to pick them up. And he always does. The system autodialed him five days ago to say his prescriptions were ready. Today, he presents to pick up a prescription for sacubitril- valsartan that the cardiologist sent yesterday. Which of the following medications should you remove from the auto-refill bag?

Atenolol

Lisinopril

Metolazone

Metoprolol

Richard asks for counseling on his new medication. Which question could a pharmacist ask to tailor counseling for Richard?

Why do you think you need more counseling?

Can you tell me what you already know about your medications?

Would it be OK if I just print the medication information sheets?

Have you ever had two hospital admissions within 30 days?

Eloise, an 85-year-old woman who has had HF for quite some time, asks the technician to help her find cough drops and cough medicine. She's been coughing for several months. It is a dry cough, and she periodically coughs so much that she can hardly talk. Her medications are unknown. The technician asks the pharmacist what to do. What is a likely option?

Ask the technician to show Eloise where the cough medicines are and recommend guaifenesin

Ask the technician to show Eloise to the counseling room so you can review her profile

Ask the technician to tell Eloise that the best approach is to increase hydration

Ask the technician to tell Eloise to call her physician because she's on lisinopril

References

Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2022 May 3;145(18):e1033. doi: 10.1161/CIR.0000000000001073] [published correction appears in Circulation. 2022 Sep 27;146(13):e185. doi: 10.1161/CIR.0000000000001097] [published correction appears in Circulation. 2023 Apr 4;147(14):e674. doi: 10.1161/CIR.0000000000001142]. Circulation. 2022;145(18):e895- e1032. doi:10.1161/CIR.0000000000001063

Centers for Disease Control and Prevention. About Heart Failure. May 15, 2024. https://www.cdc.gov/heart-disease/about/heart-failure.html.

Accessed October 19, 2024.

Virani SS, Alonso A, Benjamin EJ, et al. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020;141(9):e139-e596. doi:10.1161/CIR.0000000000000757

National Heart, Lung, and Blood Institute. How Blood Flows through the Heart. Updated March 24, 2022. https://www.nhlbi.nih.gov/health/heart/blood-flow. Accessed October 19, 2024.

American Lung Association. Your Heart and Lungs: The Ultimate Relationship. February 13, 2023. https://www.lung.org/blog/heart-lung-

relationship. Accessed October 19, 2024.

Orsborne C, Chaggar PS, Shaw SM, Williams SG. The renin-angiotensin- aldosterone system in heart failure for the non-specialist: the past, the present and the future. Postgrad Med J. 2017;93(1095):29-37. doi:10.1136/postgradmedj-2016-134045

Cleveland Clinic. Renin-Angiotensin-Aldosterone System (RAAS). Updated September 13, 2022. https://my.clevelandclinic.org/health/articles/24175-renin-angiotensin- aldosterone-system-raas. Accessed October 19, 2024.

American Heart Association. Classes and Stages of Heart Failure. Updated June 7, 2023. https://www.heart.org/en/health-topics/heart- failure/what-is-heart-failure/classes-of-heart-failure. Accessed October 19, 2024.

Lee MMY, Sattar N, McMurray JJV, Packard CJ. Statins in the Prevention and Treatment of Heart Failure: a Review of the Evidence. Curr Atheroscler Rep. 2019;21(10):41. Published 2019 Jul 27. doi:10.1007/s11883-019-0800-z

Entresto (prescribing information). Novartis; 2024. https://www.novartis.com/us-en/sites/novartis_us/files/entresto.pdf. Accessed October 19, 2024.

Shah A, Gandhi D, Srivastava S, Shah KJ, Mansukhani R. Heart Failure: A Class Review of Pharmacotherapy. P T. 2017;42(7):464-472.

Farxiga (prescribing information). AstraZeneca; 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/202293s0 31lbl.pdf. Accessed October 19, 2024.

Jardiance (prescribing information). Boehringer Ingelheim; 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/204629s0 40lbl.pdf. Accessed October 19, 2024.

Inpefa (prescribing information). Lexicon Pharmaceuticals; 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216203s0 00lbl.pdf. Accessed October 19, 2024.

Mascolo A, di Mauro G, Cappetta D, et al. Current and future therapeutic perspective in chronic heart failure. Pharmacol Res. 2022;175:106035. doi:10.1016/j.phrs.2021.106035

Rubin S, Tomaszewski M. Prediction and prevention of ACE-inhibitor- induced angioedema-an unmet clinical need in management of hypertension. Hypertens Res. 2024;47(2):257-260. doi:10.1038/s41440-023-01491-9

Pabel S, Hamdani N, Luedde M, Sossalla S. SGLT2 Inhibitors and Their Mode of Action in Heart Failure-Has the Mystery Been Unravelled?. Curr Heart Fail Rep. 2021;18(5):315-328. doi:10.1007/s11897-021-00529-8

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Wiggins BS, Rodgers JE, DiDomenico RJ, Cook AM, Page RL 2nd. Discharge counseling for patients with heart failure or myocardial infarction: a best practices model developed by members of the American College of Clinical Pharmacy's Cardiology Practice and Research Network based on the Hospital to Home (H2H) Initiative. Pharmacotherapy. 2013;33(5):558-580. doi:10.1002/phar.1231

DISCLAIMER

The information provided in this course is general in nature, and it is solely designed to provide participants with continuing education credit(s). This course and materials are not meant to substitute for the independent, professional judgment of any participant regarding that participant’s professional practice, including but not limited to patient assessment, diagnosis, treatment, and/or health management. Medical and pharmacy practices, rules, and laws vary from state to state, and this course does not cover the laws of each state; therefore, participants must consult the laws of their state as they relate to their professional practice.

Healthcare professionals, including pharmacists and pharmacy technicians, must consult with their employer, healthcare facility, hospital, or other organization, for guidelines, protocols, and procedures they are to follow. The information provided in this course does not replace those guidelines, protocols, and procedures but is for academic purposes only, and this course’s limited purpose is for the completion of continuing education credits.

Participants are advised and acknowledge that information related to medications, their administration, dosing, contraindications, adverse reactions, interactions, warnings, precautions, or accepted uses are constantly changing, and any person taking this course understands that such person must make an independent review of medication information prior to any patient assessment, diagnosis, treatment and/or health management. Any discussion of off-label use of any medication, device, or procedure is informational only, and such uses are not endorsed hereby.

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