Acute Care in Cardiology PDF

Acute Care in Cardiology iii. A  AD therapy (amiodarone, flecainide, mexiletine, propafenone, sotalol) may be considered to improve symptoms associated with arrhythmias in patients receiving adequate doses of a β-blocker or CCB (class IIb; LOE C). (a) Flecainide and propafenone are not reco...

Acute Care in Cardiology iii. A  AD therapy (amiodarone, flecainide, mexiletine, propafenone, sotalol) may be considered to improve symptoms associated with arrhythmias in patients receiving adequate doses of a β-blocker or CCB (class IIb; LOE C). (a) Flecainide and propafenone are not recommended to suppress premature ventricular contractions in patients with reduced LV function (class III). (b) Sotalol should be used with caution in patients with chronic kidney disease and should be avoided in patients with a prolonged QT interval at baseline or excessive prolongation of QT interval (500 milliseconds) on therapy initiation (class I; LOE B). (c) Amiodarone appears to have less overall proarrhythmic risk than other AADs in patients with HF and may be preferred to other membrane-active AADs unless a functioning defibrillator has been implanted (class IIb; LOE C). iv. Amiodarone, sotalol, and other β-blockers are useful after defibrillator implantation to reduce shocks and suppress nonsustained VT in patients who are unsuitable for ICD therapy, in addition to optimal medical therapy for patients with HF. 2. Sustained VT a. Immediate fibrillation for pulseless VT b. Synchronized cardioversion for VT with pulse c. Evaluate cardiac structure and function. d. ICD indicated for most patients with SHD G. Implantable Cardioverter-Defibrillators 1. For primary prevention of SCD a. LVEF of 35% or less that is caused by ischemic heart disease who are at least 40 days post-MI and at least 90 days postrevascularization, and with NYHA class II or III HF despite GDMT b. In patients with LVEF of 30% or less that is caused by ischemic heart disease who are at least 40 days post-MI and at least 90 days postrevascularization, and with NYHA class I HF despite GDMT c. Nonischemic cardiomyopathy, HF with NYHA class II–III symptoms, and an LVEF of 35% or less, despite at least 3 months of GDMT d. Syncope with SHD and inducible VT/VF during electrophysiologic study e. High risk of life-threatening VT/VF; congenital long QT syndrome with recurrent symptoms or torsades de pointes while receiving a β-blocker f. Must have reasonable survival expectation for more than 1 year 2. For secondary prevention of SCD a. Previous episode of resuscitated VT/VF, hemodynamically unstable VT with no completely reversible cause, or sustained VT in presence of heart disease b. Should receive optimal chronic medications (β-blockers, ACE inhibitors) unless contraindicated c. Must have reasonable survival expectation for more than 1 year 3. General medication considerations with ICD a. β-Blockers i. Considered mainstay therapy ii. Effective in suppressing ventricular ectopic beats and in reducing SCD in a spectrum of cardiac disorders in patients with and without HF (nonsustained VT) b. Amiodarone i. No better than ICD in reducing SCD as a lone agent; no mortality benefit ii. Can be used to treat symptomatic nonsustained VT if β-blockers not effective when ICD not indicated iii. Can be used in combination with β-blockers to decrease firing of ICD (defibrillator storm) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-48 Acute Care in Cardiology c. Sotalol i. No mortality advantage ii. Can suppress VT and be used to decrease frequency of ICD firing iii. Greater proarrhythmic potential; avoid in patients with severely depressed LVEF or significant HF; renal dosing necessary H. Treatment of Arrhythmias in Special Patient Populations 1. Heart failure a. Avoid class Ia and class Ic agents. b. Amiodarone and dofetilide (used for atrial arrhythmias only) have a neutral effect on mortality in patients with LV dysfunction after an MI. c. Dronedarone (used in atrial arrhythmias only) is contraindicated in patients with symptomatic HF with recent decompensation necessitating hospitalization or NYHA class IV symptoms; risk of death was doubled in these patients. 2. Acute MI a. Avoid class Ia and class Ic agents. b. CAST trial with class Ic agents (encainide, flecainide) showed greater mortality when used to treat post-MI non–life-threatening ventricular arrhythmias; avoid class Ic agents in patients with SHD. c. Class Ia medications: Increased mortality in MI survivors d. Amiodarone and dofetilide (used for atrial arrhythmias only) have a neutral effect on mortality in patients with LV dysfunction after an MI. I. Drug-Induced Arrhythmias: Review all potential drug etiologies and treat appropriately. 1. Drug-induced QT prolongation a. Discontinue offending agent if QT prolongation is significant. b. Ensure proper renal and hepatic dosing adjustments. c. Review electrolyte abnormalities and thyroid function tests. d. Ensure that all electrolytes are maintained at critical concentrations: K+ greater than 4–5 mEq/L and magnesium greater than 2 mg/dL. e. Ensure that all ECG parameters are within normal limits. f. Limitations to QTc calculations include consideration of QRS duration, ventricular conduction delays, ventricular pacemakers, arrhythmias, and QT correction based on ventricular rate. 2. Drug-induced bradycardia or atrioventricular block a. β-Blocker, CCB, digoxin b. Administer antidote, if appropriate (e.g., calcium for CCB toxicity). 3. Review for drug interactions. AADs have drug interactions that may cause significant outcomes. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-49 AL GRAWANY Acute Care in Cardiology IV. HYPERTENSIVE CRISES A. Definitions 1. Hypertensive emergency a. Severe elevations in blood pressure (usually greater than 180/120 mm Hg) with evidence of new or worsening target-organ damage b. Acute target-organ damage can include hypertensive encephalopathy, intracranial hemorrhage, acute ischemic stroke, or other acute neurologic deficit; UA or acute MI; acute LV failure with pulmonary edema; aortic dissection; retinopathy or papilledema; decreased urinary output or acute renal failure; eclampsia c. Actual blood pressure may not be as important as the rate of blood pressure rise. d. Requires immediate blood pressure lowering (not necessarily to normal ranges) to prevent or limit further target-organ damage 2. Hypertensive urgency a. Situations associated with severe blood pressure elevation in otherwise stable patients without acute or impending change in target-organ damage or dysfunction b. Short-term risk is not as high; therefore, blood pressure reduction occurs over several days, not immediately. B. Goals and Treatment 1. Hypertensive emergency a. Goal is to minimize target-organ damage safely by rapid recognition of the problem and early initiation of appropriate antihypertensive treatment. b. Patients are usually admitted for intensive care unit care and close follow-up. c. Lower MAP by no more than 25% in the first hour; then reduce SBP to 160 mm Hg and DBP to 100–110 mm Hg over next 2–6 hours; then to normal over next 24–48 hours d. Exceptions: i. Do not lower blood pressure in acute ischemic stroke unless greater than 220/120 mm Hg or greater than 185/110 mm Hg in thrombolysis candidates. ii. Lower SBP to less than 140 mm Hg in the first hour of treatment in severe preeclampsia or eclampsia and in pheochromocytoma with hypertensive crisis. iii. Lower SBP to less than 120 mm Hg and HR less than 60 beats/minute in the first hour of treatment in aortic dissection. e. Intravenous medications used commonly (Table 21) f. No randomized evidence to suggest one drug of choice because of small trial size, lack of long-term follow-up, and failure to report outcomes g. Two trials have shown that nicardipine is better than labetalol in achieving the short-term blood pressure target. h. Agents are chosen on the basis of drug pharmacology, pathophysiologic factors underlying the patient’s hypertension, degree of progression of target-organ damage, desirable rate of blood pressure decline, and presence of patient characteristics (Tables 21 and 22). i. No randomized evidence exists comparing different strategies to reduce blood pressure, except in patients with intracranial hemorrhage. j. No randomized evidence suggests how rapidly to reduce blood pressure. k. Clinical experience indicates that excessive reductions in blood pressure can cause renal, cerebral, or coronary ischemia and should be avoided. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-51 Acute Care in Cardiology 2. Hypertensive urgency a. Treated by reinstitution or intensification of antihypertensive drug therapy b.  No indication for referral to the ED, immediate reduction in blood pressure in the ED, or hospitalization c. No proven benefit exists from rapid reductions in blood pressure. d. Choice of agent used in this setting varies, and in many cases, adjusting chronic oral therapy (increasing doses), reinitiating therapy in the nonadherent, or adding a new agent (i.e., diuretic) to long-term therapy is appropriate. Use of intravenous agents has been associated with adverse events and prolonged hospitalization e. All patients with hypertensive urgency should be reevaluated within 7 days (preferably after 1–3 days). C. Treatment Options (Table 21) Table 21. Commonly Used IV Drugs for Hypertensive Emergencies Drug (onset, duration) IV Dose Comments/AEs 0.3–0.5 mcg/kg/min, increase in increments of 0.5 mcg/kg/min to achieve BP target; max 10 mcg/kg/ min; for infusion rates ≥ 4–10 mcg/ kg/min or duration > 30 min Intra-arterial BP monitoring recommended to prevent “overshoot”; lower doses required in older adult patients; tachyphylaxis may occur with extended use Vasodilators Sodium nitroprusside (Nipride) (immediate, 2–3 min) AEs: Cyanide or thiocyanate toxicity with prolonged use can result in irreversible neurologic changes and cardiac arrest, nausea, vomiting, methemoglobinemia CIs: Renal, hepatic failure Caution: Elevated ICP, may cause coronary steal in setting of coronary ischemia Nitroglycerin (2–5 min, 5–10 min) 5–10 mcg/min, increase in increments of 5 mcg/min every 3–5 min to a max 200 mcg/min Use only in patients with ACS and/or acute pulmonary edema; do not use in volume-depleted patients or in patients with right ventricular infarction AEs: Headache, nausea, vomiting, tachyphylaxis Hydralazine (Apresoline) (10 min, 1–4 hr) 5–10 mg by slow IV infusion every 4–6 hr (NTE initial 20 mg/dose) BP begins to decrease within 10–30 min, and lasts 2–4 hr; unpredictability of response and prolonged duration of action make hydralazine less desirable first agent AEs: Reflex tachycardia, headache, flushing Caution: Angina or MI, elevated ICP, aortic dissection Enalaprilat (Vasotec) (within 30 min, 12–24 hr) 0.625–1.25 mg over 5 min; doses can be increased up to max 5 mg every 6 hr Should not be used in acute MI; mainly useful in hypertensive emergencies associated with high plasma renin activity; dose not easily adjusted; relatively slow onset (15 min), long half-life, and unpredictability of BP response AEs: Renal insufficiency or failure, hyperkalemia CIs: Pregnancy, bilateral renal artery stenosis, angioedema ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-52 Acute Care in Cardiology Table 21. Commonly Used IV Drugs for Hypertensive Emergencies (Cont’d) Drug (onset, duration) IV Dose Comments/AEs 0.1–0.3 mcg/kg/min, increased by 0.05–0.1 mcg/kg/min every 15 min to a max of 1.6 mcg/kg/min Contraindicated in patients at risk of increased intraocular pressure (glaucoma) or ICP and those with sulfite allergy Vasodilators Fenoldopam (Corlopam) (< 5 min, 30 min) AEs: Headache, flushing, tachycardia, cerebral ischemia Nicardipine (Cardene) (1–5 min, 15–30 min; up to 4 hr if prolonged infusion) 5 mg/hr, increased by 2.5 mg/hr every –15 min to a max 15 mg/hr Contraindicated in advanced aortic stenosis; no dose adjustment needed for older patients AEs: Reflex tachycardia, nausea, vomiting, headache, flushing Caution: Angina or MI, acute HF Clevidipine (Cleviprex) (2–4 min, 5–15 min) 1–2 mg/hr, doubling every 90 s until BP approaches target, then increasing by less than double every 5–10 min; max 32 mg/hr; max duration 72 hr Patients with renal failure and hepatic failure and older adults not specifically studied – use low-end range for older adults; contraindicated in soy or egg product allergy, severe aortic stenosis, defective lipid metabolism (e.g., pathologic hyperlipidemia, lipoid nephrosis, or acute pancreatitis) Caution: HF, concomitant β-blocker use, reflex tachycardia, rebound HTN Adrenergic Inhibitors Esmolol (Brevibloc) (1–2 min, 10–30 min) LD 500–1000 mcg/kg IVB over 1 min, then a 50-mcg/kg/min infusion; titrated every 5 min in 50-mcg/kg/min increments as needed to a max 200 mcg/kg/min Contraindicated in patients with concurrent β-blocker therapy, bradycardia, or decompensated HF AEs: Bronchospasm, HF exacerbation, bradycardia or heart block Caution: May worsen acute HF, asthma (higher doses may block β2-receptors and affect lung function in reactive airway disease), heart block Labetalol (Normodyne, Trandate) (5–10 min, 3–6 hr) 20–80 mg every 15 min or initial 0.3–1 mg/kg dose (max 20 mg) slow IV injection every 10 min or 0.4–1.0 mg/kg/hr infusion up to max 3 mg/ kg/hr Contraindicated in reactive airway disease or chronic obstructive pulmonary disease; especially useful in hyperadrenergic syndromes; may worsen HF and should not be given in patients with secondor third-degree heart block or bradycardia Caution: Prolonged hypotension may occur with overtreatment Phentolamine (2 min, 15–30 min) IVB dose 1–5 mg; additional bolus doses every 10 min as needed Used in hypertensive emergencies induced by catecholamine excess (pheochromocytoma, monamine oxidase inhibitors interactions with food and/or drugs, cocaine toxicity, amphetamine overdose, or clonidine withdrawal) CI = contraindication; ICP = intracranial pressure. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-53 Acute Care in Cardiology Table 22. Agents Preferred for Hypertensive Crises According to Comorbidities Comorbidity Preferred Agents Comments Acute aortic dissection Labetalol, esmolol Requires rapid lowering of SBP to ≤ 120 mm Hg within 20 min; heart rate target <60 bpm β-blocker should be given before vasodilator (nicardipine or NTP) if needed for BP control or to prevent reflex tachycardia or inotropic effect Acute coronary syndromes Esmolol or NTG (preferred), labetalol, nicardipine Nitrates given in the presence of PDE-5 inhibitors may induce profound hypotension; contraindications to β-blockers include moderate to severe LV failure with pulmonary edema, right ventricular infarction, bradycardia (< 60 beats/min), hypotension (SBP < 100 mm Hg), poor peripheral perfusion, second- or thirddegree heart block, and reactive airway disease Acute pulmonary edema Clevidipine, NTG, NTP β-Blockers contraindicated; NTG preferred for ADHF Acute renal failure Clevidipine, fenoldopam, nicardipine Eclampsia or preeclampsia Labetalol, nicardipine, hydralazine (second line) Requires rapid BP lowering to < 140 mm Hg within first hour; ACE inhibitor, ARBs, renin inhibitors, and NTP contraindicated Perioperative HTN (BP ≥ 160/90 mm Hg or SBP elevation > 20% of the preoperative value that persists > 15 min) Clevidipine, esmolol, nicardipine, NTG Intraoperative HTN is most common during anesthesia induction and airway manipulation Acute sympathetic discharge or catecholamine excess states (e.g., pheochromocytoma, post-carotid endarterectomy status) Clevidipine, nicardipine, phentolamine Requires rapid lowering of BP Acute intracranial hemorrhage IV continuous infusion (Note: Avoid unopposed β-blockade) Most studied agents in this setting are nicardipine, clevidipine, labetalol Acute ischemic stroke No preference of agent Lower BP in those who present with SBP > 220 mm Hg with continuous IV infusion and close BP monitoring; immediate lowering of SBP < 140 mm Hg is not of benefit and may be harmful. Avoiding medications that can increase ICP and worsen cerebral ischemia (hydralazine, NTG, and NTP) Early initiation or resumption of antihypertensive treatment indicated only in (1) patients treated with tissue-type plasminogen activator to BP < 185/110 mm Hg and (2) patients with SBP > 220 mm Hg or DBP > 120 mm Hg; cerebral autoregulation in the ischemic penumbra of the stroke is grossly abnormal and rapid reduction of BP can be harmful; reinitiate antihypertensive therapies in those with preexisting HTN after neurologic stability ARB = angiotensin receptor blocker; NTP = nitroprusside. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-54 Chronic Care in Cardiology v. Cardiotoxins (a) Alcohol (b) Cocaine (c) Chemotherapeutic agents (1) Anthracyclines (2) Cyclophosphamide (high dose) (3) Fluorouracil (4) Trastuzumab with or without pertuzumab/hyaluronidase (5) Mitoxantrone vi. Myocarditis vii. Idiopathic viii. Tachycardia ix. Peripartum 3. Heart failure with preserved EF (HFpEF) a. Defined as an LVEF of 50% or greater; borderline HFpEF is LVEF 41%–49% b. Accounts for about 50% (highly variable) of patients with HF c. Impaired ventricular relaxation and filling d. Normal wall motion e. Most common cause is HTN (60%–89%). 4. Primary symptoms a. Dyspnea b. Fatigue c. Edema d. Exercise intolerance 5. Stages and functional class of HF according to the American College of Cardiology/American Heart Association (ACC/AHA) (Table 1) Table 1. HF Stages and Corresponding NYHA Functional Class A B C ACC/AHA Stage At high risk of HF (uncontrolled risk factors) but without structural heart disease, cardiac biomarkers of stretch or injury, or symptoms of HF No signs or symptoms of HF but with structural heart disease, increased filling pressures, and/or risk factors + either increased BNP or persistently elevated troponin Structural heart disease with prior or current symptoms of HF NYHA Functional Class None I Asymptomatic HF; no limitations in physical activity caused by HF symptoms I No limitations in physical activity caused by HF symptoms II Slight limitation of physical activity; asymptomatic at rest, but symptoms of HF with normal level of activity III Marked limitations in physical activity because of HF symptoms; asymptomatic at rest IV Symptoms of HF at rest or unable to carry out any physical activity ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-74 Chronic Care in Cardiology Table 1. HF Stages and Corresponding NYHA Functional Class (Cont’d) D ACC/AHA Stage Marked HF symptoms that interfere with daily life and recurrent hospitalizations despite attempts to optimize guidelinedirected medical therapy IV NYHA Functional Class Symptoms of HF at rest ACC = American College of Cardiology; AHA = American Heart Association; HF = heart failure; NYHA = New York Heart Association. Adapted from: 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. Circulation 2022;79:1757-80. 6. Goals of therapy a. Modify or control risk factors (e.g., HTN, obesity, DM) b. Manage structural heart disease c. Reduce morbidity and mortality d. Prevent or minimize Na and water retention e. Eliminate or minimize HF symptoms f. Block compensatory neurohormonal activation caused by reduced cardiac output (CO) g. Slow progression of worsening cardiac function B. H  FrEF 1. Pharmacologic therapy (Figure 1) a. General approach to therapy i. Initiation and titration of optimal medication therapy in HFrEF should prioritize angiotensin receptor-neprilysin inhibitor (ARNI), β-blocker, mineralocorticoid receptor antagonist (MRA), and sodium-glucose cotransporter 2 (SGLT2) inhibitor use to reduce CV mortality and HF hospitalizations (Figure 1). ii. The order of medication initiation does not necessarily need to follow the sequence of trial publications. Rather, an individualized approach to initiation and sequencing guided by patient symptoms, vital signs, tolerance, renal function, electrolytes, comorbidities, functional status, and ability to follow up is recommended. iii. Titration and optimization can occur as frequently as every 1–2 weeks. iv. After optimizing ARNI, β-blocker, MRA, SGLT2 inhibitor, and diuretic therapy, additional agents can be considered on the basis of patient factors (Figure 1). b. ACE inhibitors i. Place in therapy: (a) Recommended in all patients with HFrEF and current or prior symptoms when use with an ARNI is not feasible, unless contraindicated (class I indication) (b) Often better tolerated than ß-blockers as first-line agents in patients with signs and symptoms of congestion/fluid overload ii. Benefits (a) Decreased mortality (about 25%–50% relative risk reduction compared with placebo depending on severity of HF) (b) Decreased hospitalizations (about 30% relative risk reduction compared with placebo) (c) Symptom improvement (d) Improved clinical status (e) Improved sense of well-being (f) Notable trials: CONSENSUS (enalapril), SOLVD (enalapril), SAVE (captopril), AIRE (ramipril), and TRACE (trandolapril). ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-75 Chronic Care in Cardiology Figure 1. Algorithm for pharmacologic management of heart failure with reduced ejection fraction. HFmrEF is defined as a left ventricular ejection fraction (LVEF) of 41%–49% with evidence of spontaneous or provokable increased LV filling pressures. b HFimpEF is defined as HF with a previous LVEF ≤ 40% and a follow-up measurement of LVEF > 40%. ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; ARNI = angiotensin receptor-neprilysin inhibitor; HF = heart failure; HFimpEF = HF with improved ejection fraction; HFmrEF = HF with mildly reduced EF; HFpEF = HF with preserved EF; HFrEF = HF with reduced EF; LVEF = left ventricular EF; MRA = mineralocorticoid receptor antagonist (e.g., spironolactone, eplerenone); NP = natriuretic peptide; NYHA = New York Heart Association; PUFA = polyunsaturated fatty acid; RAAS = renin-angiotensin-aldosterone system; SGLT2i = sodium-glucose cotransporter 2 inhibitor. a ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-76 Chronic Care in Cardiology iii. Mechanism of action (a) Blocks production of angiotensin II (1) Decreases sympathetic stimulation (2) Decreases production of aldosterone and vasopressin (3) Decreases vasoconstriction (afterload and preload) (b) Increases bradykinins (decreases their metabolism) (1) Increases vasodilatory prostaglandins (2) May attenuate myocardial remodeling iv. Dosing and administration considerations (a) Start low and double the dose every 1–4 weeks to target dose (Table 2). (b) ATLAS trial comparing patients with systolic dysfunction who received low-dose lisinopril (2.5–5 mg/day) and patients who received high-dose lisinopril (32.5–35 mg/day) showed no difference in all-cause mortality or CV mortality; however, the high-dose group did have a significant 12% lower risk of death or hospitalization for any reason and 24% fewer hospitalizations for HF. (c) Patients may notice improvement in symptoms in several weeks. (d) Avoid use in patients who have experienced angioedema as the result of previous ACE inhibitor use or those who are pregnant or plan to become pregnant. (e) Use caution if SBP is less than 80 mm Hg, SCr is greater than 3 mg/dL, K is greater than 5.0 mEq/L, or the patient has bilateral renal artery stenosis. v. Monitoring (a) Monitor SCr and K for 1–2 weeks after initiating therapy or increasing the dose, especially in high-risk patients (preexisting hypotension, DM, K supplements, azotemia). SCr may rise (up to a 30% increase is acceptable) because of renal efferent artery dilation (results in a slightly decreased glomerular filtration rate). Rarely, acute renal failure occurs, especially if the patient is intravascularly depleted. Be careful to avoid overdiuresis. (b) Monitor BP and symptoms of hypotension (e.g., dizziness, lightheadedness). (1) BP may be low to begin with because of low CO. (2) BP = CO × Systemic vascular resistance (SVR). (3) In HF, as CO increases because of decreased SVR, BP may decrease slightly or remain the same. (4) Symptoms of hypotension are often not present with small dose increases. Remember to treat the patient, not the number. (c) Ninety percent of people tolerate ACE inhibitors. (1) A ngioedema (less than 1%): Can switch to angiotensin II receptor blockers (ARBs; cross-reactivity is 2.5%) or hydralazine–isosorbide dinitrate (2) Cough (20%): Can switch to ARBs (less than 1%) Table 2. ACE Inhibitors and Recommended Dosing Drug Captopril Enalapril Lisinopril Perindopril Ramipril Trandolapril Starting Dosage 6.25 mg three times daily 2.5 mg twice daily 2.5–5 mg daily 2 mg daily 1.25–2.5 mg daily 1 mg daily Target Dosage 50 mg three times daily 10 mg twice daily 20 mg daily 8 mg daily 10 mg daily 4 mg daily Note: Fosinopril and quinapril can be used; however, they do not have the same magnitude of mortality-reducing data as listed above. ACE = angiotensin-converting enzyme ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-77 Chronic Care in Cardiology c. Angiotensin receptor blockers i. Place in therapy (a) Recommended in patients with HFrEF with current or prior symptoms who are unable to take an ACE inhibitor or ARNI (class I indication). Have not been proven superior to ACE inhibitors at target HF dosages. (b) Possibly considered if patient has experienced ACE inhibitor–induced angioedema (cross-reactivity 2.5%) (c) Often better tolerated than ß-blockers as first-line agents in patients with signs and symptoms of congestion/fluid overload ii. Benefits (a) Decreased HF-related hospitalizations and decreased death from CV causes. (b) Notable clinical trials: CHARM-Alternative (candesartan), VALIANT (valsartan), VALHEFT (valsartan), and HEAAL (losartan). iii. Mechanism of action (a) Selectively block the binding of angiotensin II to the angiotensin I receptor (b) Deters vasoconstriction and aldosterone-secreting effects (c) Does not affect ACE or inhibit kinin catabolism iv. Dosing and administration (a) Start low and double the dose every 1–4 weeks to target dose (Table 3). (b) Patients may notice improvement in symptoms in several weeks. (d) Avoid use in patients who have angioedema because of previous ARB use or those who are pregnant or plan to become pregnant. (e) Use caution if SBP is less than 80 mm Hg, SCr is greater than 3 mg/dL, K is greater than 5.0 mEq/L, or the patient has bilateral renal artery stenosis. v. Monitoring (a) SCr and K 1–2 weeks after initiating therapy or increasing the dose, especially in highrisk patients (preexisting hypotension, DM, K supplements, azotemia) (1) SCr may rise (up to a 30% increase is acceptable) because of renal efferent artery dilation (results in a slightly decreased glomerular filtration rate). (2) Rarely, acute renal failure occurs, especially if the patient is intravascularly depleted (be careful to avoid overdiuresis). (b) Monitor BP and symptoms of hypotension (e.g., dizziness, lightheadedness). (c) Other adverse reactions (1) Angioedema (rare) (2) Cough (less than 1%) Table 3. ARBs and Recommended Dosing Drug Candesartan Losartan Valsartan Starting Dosage 4–8 mg daily 25–50 mg daily 20–40 mg twice daily Target Dosage 32 mg daily 150 mg daily 160 mg twice daily ARB = angiotensin receptor blocker. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-78 Chronic Care in Cardiology d. Sacubitril/valsartan i. Place in therapy (a) According to the 2022 ACC/AHA/Heart Failure Society of America (HFSA) HF guidelines (1) ARNIs are recommended for patients with chronic HFrEF to reduce morbidity and mortality (class I recommendation) . ARNIs are recommended over ACE inhibitors or ARBs, when feasible (class I recommendation), as part of a direct-to-ARNI approach. (2) In patients with chronic symptomatic NYHA class II or III HFrEF who can tolerate an ACE inhibitor or ARB, replacement by sacubitril/valsartan is recommended to further reduce morbidity and mortality (class I recommendation). ii. Benefits (a) Decreased composite endpoint of death from CV causes or hospitalization for HF (20% relative risk reduction compared with enalapril monotherapy) (b) Decreased all-cause mortality (16% relative risk reduction) and CV death (20% relative risk reduction) compared with enalapril monotherapy (c) Decreased hospitalization for HF (21% relative risk reduction compared with enalapril monotherapy) (d) Notable clinical trial: PARADIGM-HF iii. Mechanism of action (a) Sacubitril—prodrug metabolized to an active metabolite that inhibits neprilysin, increasing levels of natriuretic peptides (b) Valsartan—ARB, selectively blocks the angiotensin I receptor and inhibits angiotensin II–dependent aldosterone release iv. Dosing and administration considerations (a) Initial dose (1) Not currently taking ACE inhibitor or ARB, switching from low dose ACE inhibitor (e.g., total daily dose of enalapril ≤10 mg, lisinopril ≤ 10 mg, ramipril ≤5 mg, or equivalent) or ARB (e.g., total daily dose of valsartan ≤160 mg, losartan ≤50 mg, olmesartan ≤10 mg, or equivalent), or eGFR <30 mL/min/m2: sacubitril 24 mg/ valsartan 26 mg twice daily (2) Switching from a standard dose ACE inhibitor (e.g., total daily dose of enalapril >10 mg, lisinopril >10 mg, ramipril >5 mg, or equivalent) or ARB (e.g., total daily dose of valsartan >160 mg, losartan >50 mg, olmesartan >10 mg, or equivalent): sacubitril 49 mg/valsartan 51 mg twice daily (b) Maintenance dose: Double the dose every 2–4 weeks to a target dose of sacubitril 97 mg/ valsartan 103 mg twice daily, as tolerated. (c) If switching from an ACE inhibitor, allow a 36-hour washout period before initiating sacubitril/valsartan. (d) Because sacubitril is a neprilysin inhibitor, BNP will increase with use. However, NT-proBNP levels will not change. v. Monitoring (a) Observe for signs and symptoms of angioedema and hypotension. (b) Monitor renal function and K 1–2 weeks after initiating therapy or increasing the dose, especially in high-risk patients (e.g., preexisting hypotension, DM, K supplements, azotemia). (c) Monitor fluid status because patients may require a dose reduction in diuretic therapy. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-79 AL GRAWANY Chronic Care in Cardiology e. β-blockers i. Place in therapy: (a) Recommended in all patients with HFrEF with current or prior symptoms unless contraindicated (class I indication) (b) Often better tolerated than than ACE inhibitors/ARBs/angiotensin receptor-neprilysin inhibitors (ARNIs) as first-line agents in patients without signs and symptoms of congestion/fluid overload ii. Benefits (when added to an ACE inhibitor) (a) Decreased mortality (about 35% relative risk reduction compared with placebo) (b) Decreased hospitalizations (about 25% relative risk reduction compared with placebo) (c) Symptom improvement (d) Improved clinical status (e) Notable clinical trials: CIBIS II (bisoprolol), MERIT-HF (metoprolol succinate), COPERNICUS (carvedilol), and COMET (metoprolol tartrate vs. carvedilol). iii. Mechanism of action (a) Blocks the effect of norepinephrine and other sympathetic neurotransmitters on the heart and vascular system (1) Decreases ventricular arrhythmias (sudden cardiac death) (2) Decreases cardiac hypertrophy and cardiac cell death (3) Decreases vasoconstriction and HR (b) Carvedilol also provides α1-blockade. (1) Further decreases SVR (afterload) (2) Results in greater reduction in BP than metoprolol succinate iv. Dosing and administration considerations (a) Only bisoprolol, carvedilol, and metoprolol succinate are recommended in HFrEF. (b) Initiate when HF symptoms are stable and patients are euvolemic. (c) Should not be prescribed without diuretics in patients with current or recent history of fluid retention. (d) Start low and increase (double) the dose every 1– 2 weeks (or slower, if needed) to target dose. Aim to achieve target dose in 8–12 weeks (Table 4). (e) Avoid abrupt discontinuation; can precipitate clinical deterioration (f) Might not notice improvement in symptoms for several months (g) Should be considered even in patients with reactive airway disease or asymptomatic bradycardia Table 4. β-Blockers and Recommended Dosing Agent Bisoprolol Carvedilol Carvedilol CR Metoprolol succinate 50 mg twice daily if weight > 85 kg. CR = controlled release Starting Dosage 1.25 mg daily 3.125 mg twice daily 10 mg daily 12.5–25 mg daily Target Dosage 10 mg daily 25 mg twice dailya 80 mg daily 200 mg daily a ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-80 Chronic Care in Cardiology v. f. Monitoring (a) BP, HR, and symptoms of hypotension or bradycardia (monitor in 1–2 weeks) (1) Significant hypotension, bradycardia, or dizziness occurs in about 1% of patients when the β-blocker is titrated slowly. If these symptoms appear, lower the dose by 50%. (2) Of importance, remember that higher β-blocker doses are associated with greater mortality reduction. Therefore, if hypotension alone is the problem, try reducing the ACE inhibitor (or another antihypertensive) first or scheduling one agent at bedtime and one in the morning. (b) Increased edema or fluid retention (monitor in 1–2 weeks) (1) One percent to 2% more common than with placebo (in euvolemic, stable patients) (2) Responds to diuretic increase (3) Do not increase ß-blocker dose during episodes of fluid retention after therapy initiation or dose titration. (c) Fatigue or weakness (1) One percent to 2% more common than with placebo (2) Usually resolves spontaneously in several weeks (3) May require dosage decrease or discontinuation Mineralocorticoid receptor antagonists (MRAs) i. Place in therapy (a) Recommended in patients with NYHA class II–IV with an LVEF of 35% or less to reduce morbidity and mortality unless a contraindication exists. Patients with NYHA class II should have a history of CV hospitalization or elevated brain natriuretic peptide (BNP) levels (class I indication). (b) Recommended to reduce morbidity and mortality in patients after a myocardial infarction (MI) with an LVEF less than or equal to 40% with symptoms of HF or an LVEF less than 40% and DM (class I indication). ii. Benefits of spironolactone in NYHA class III and IV HF (RALES trial) (a) Decreased mortality (30% relative risk reduction compared with placebo) (b) Decreased hospitalizations for HF (35% relative risk reduction compared with placebo) (c) Improved symptoms iii. Benefits of eplerenone (selective MRA) in NYHA class II HF (EMPHASIS-HF) (a) Decreased composite endpoint of death from CV causes or hospitalization from HF (37% relative risk reduction compared with placebo) (b) Decreased death from CV causes (24% relative risk reduction compared with placebo) (c) Decreased hospitalizations for HF (42% relative risk reduction compared with placebo) (d) Decreased mortality (24% relative risk reduction compared with placebo) iv. Benefits of eplerenone in left ventricular dysfunction after MI (EPHESUS) (a) Decreased mortality (15% relative risk reduction compared with placebo) (b) Decreased composite endpoint of death from CV causes or hospitalization for CV events (13% relative reduction compared with placebo) v. Mechanism of action (a) Blocks effects of aldosterone in the kidneys, heart, and vasculature (b) Decreases K and magnesium loss; decreases ventricular arrhythmias (c) Decreases Na retention; decreases fluid retention (d) Eliminates catecholamine potentiation; decreases BP (e) Blocks direct fibrotic actions on the myocardium ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-81 Chronic Care in Cardiology vi. Dosing and administration considerations (a) SCr should be less than 2.5 mg/dL for men and less than 2.0 mg/dL in women (or estimated glomerular filtration rate greater than 30 mL/minute/1.73 m2), and K should be less than or equal to 5.0 mEq/L (Table 5). (b) In the absence of hypokalemia (K less than 4.0 mEq/L), supplemental K is not recommended when taking an MRA Table 5. MRAs and Recommended Dosing eGFR ≥ 50 mL/min/1.73 m2 Initial dose Maintenance dose Eplerenone 25 mg daily 50 mg daily Spironolactone 12.5–25 mg daily 25 mg daily or BID eGFR 30-49 mL/min/1.73 m2 Initial dose Maintenance dose 25 mg 25 mg daily every other day 12.5 mg daily or 12.5–25 mg daily every other day BID = twice daily; eGFR = estimated glomerular filtration rate; MRA = mineralocorticoid receptor antagonist. g. vii. Monitoring (a) K and SCr within 2–3 days, again at 7 days after starting therapy, monthly for first 3 months, and every 3 months thereafter. If the dose of ACE inhibitor or ARB is increased, restart monitoring. (1) Hyperkalemia was reported in only 2% of the patients in trials; however, in practice, it occurs in about 20% of patients. (2) Decrease dose by 50% or discontinue if K is greater than 5.5 mEq/L. (b) Gynecomastia (1) Spironolactone: Reported at a rate of 10% in clinical trials (2) Eplerenone can be considered as an alternative to spironolactone if gynecomastia is present. SGLT2 inhibitors i. Place in therapy (a) Recommended in symptomatic HFrEF with adequate renal function regardless of DM status (1) Dapagliflozin: Indicated if eGFR is 25 mL/minute/1.73 m 2 or greater (2) Empagliflozin: Indicated if eGFR is 20 mL/minute/1.73 m2 or greater ii. Benefits (a) Dapagliflozin (DAPA-HF) and empagliflozin (EMPEROR-Reduced) have been shown to reduce the risk of CV death or worsening HF. iii. Mechanism of action (a) Inhibit the SGLT2 cotransporter in the renal proximal tubules, reducing reabsorption of filtered glucose and increasing urinary glucose excretion (b) Promote diuresis, reduce arterial pressure, and may reduce cardiac hypertrophy and fibrosis iv. Dosing (a) Dapagliflozin: 10 mg orally daily (b) Empagliflozin: 10 mg orally daily v. Monitoring (a) Monitor SCr, signs and symptoms of volume depletion, and orthostatics. Consider reducing diuretic dose because of diuretic effects. (b) Monitor blood glucose and A1C. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-82 Chronic Care in Cardiology h. i. (c) A  ssess patients presenting with signs or symptoms of metabolic acidosis for ketoacidosis. Patients may experience euglycemic diabetic ketoacidosis. Discontinue SGLT2 inhibitors before surgery to reduce the risk. (d) Monitor for signs and symptoms of mycotic genital infections and UTIs. Hydralazine/isosorbide dinitrate i. Place in therapy (a) Recommended in addition to optimal medical therapy to reduce morbidity and mortality for patients self-described as African American with NYHA class III or IV HFrEF (class I indication) (b) May be useful in patients with current or prior symptoms of HFrEF who are unable to tolerate an ARNI, ACE inhibitor, or an ARB (class IIa indication) ii. Benefits (a) Decreased mortality (43% relative risk reduction compared with placebo in African American patients) (b) Reduced pulmonary congestion and improved exercise tolerance (c) Notable clinical trials: V-HeFT and A-HeFT iii. Mechanism of action (a) Hydralazine (1) Arterial vasodilator (reduces afterload) (2) Increases effect of nitrates through antioxidant mechanisms (b) Isosorbide dinitrate (1) Stimulates nitric acid signaling in the endothelium (2) Venous vasodilator (reduces preload) iv. Dosing and administration considerations (a) Fixed-dose BiDil (hydralazine 37.5 mg plus isosorbide dinitrate 20 mg) starting at 1 tablet three times daily with a goal dose of 2 tablets three times daily (b) Hydralazine 75 to 300 mg daily in 3 or 4 divided doses; isosorbide dinitrate 60–120 mg daily in 3 or 4 divided doses v. Monitoring (a) Headache (b) Hypotension (c) Drug-induced lupus (with hydralazine) Diuretics i. Place in therapy: Indicated in patients with evidence of fluid retention (class I indication) ii. Short-term benefit (days) (a) Decreased jugular venous distension (b) Decreased pulmonary congestion (c) Decreased peripheral edema iii. Intermediate-term benefits (weeks to months) (a) Decreased daily symptoms (b) Increased exercise tolerance iv. Long-term benefits (months to years): No benefit on mortality v. Mechanism of action: Inhibit reabsorption of Na in the ascending limb of the loop of Henle (loops) or in the distal tubule (thiazides) vi. Dosing and administration considerations (Table 6) (a) Should be combined with guideline-directed medical therapy (b) Start with a low initial dose and then double the dose and titrate according to the patient’s weight as needed. Bioavailability differs between oral loop diuretics and must be considered when converting from one agent to another. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-83 Chronic Care in Cardiology (c) I f a patient has fluid overload, initiate and adjust therapy to result in 0.5-1 kg of weight loss per day (may be more aggressive in the inpatient setting). (d) Long-term therapy should be adjusted to maintain a euvolemic state. (e) A loop diuretic can be combined with another diuretic class (e.g., thiazide diuretic) for synergy, if needed. (f) Loop diuretics are preferred because of their greater diuretic capabilities; loop diuretics also retain efficacy with decreased renal function. vii. Monitoring: Monitor and replace K and magnesium as needed, especially with loop diuretics (goal with cardiovascular [CV] disease is K of 4.0 mEq/L or greater and magnesium of 2.0 mEq/L or greater to minimize the risk of arrhythmias). Monitor SCr and BUN to avoid acute kidney injury with overdiureses. Also monitor HCO3 for metabolic alkalosis with overdiuresis. Table 6. Diuretics and Recommended Dosinga Oral Initial Bioavailability (%) Daily Dose Loop Diuretics (inhibit 20%–25% of sodium reabsorption) Maximal Total Daily Dose (mg) Duration of Action (hr) Furosemideb 10–67 20–40 mg daily or BID b Bumetanide 80–100 0.5–1 mg daily or BID Torsemide 80–100 10–20 mg daily b Ethacrynic acid 100 25–50 mg daily or BID Thiazide Diuretics (inhibit 10%–15% of sodium reabsorption) 600 10 200 200 6–8 4–6 12–16 6–8 Hydrochlorothiazide Metolazone Chlorthalidone Chlorothiazideb 200 20 100 1000 6–12 12–24 24–72 6–12 Agent 65–75 40–65 64 30–50 25 mg daily or BID 2.5 mg daily 12.5–25 mg daily 250–500 daily or BID Equivalent doses: furosemide 40 mg = bumetanide 1 mg = torsemide 10–20 mg = ethacrynic acid 50 mg. Available in oral and intravenous formulations. BID = twice daily. a b j. Ivabradine i. Place in therapy (a) Novel therapy approved by the FDA in 2015 (b) According to the 2017 ACC/AHA/Heart Failure Society of America Focused Update of the HF guidelines, ivabradine can be beneficial to reduce HF hospitalizations for patients with symptomatic (NYHA class II and III), stable, chronic HFrEF (LVEF of 35% or less) who are receiving evidence-based therapies, including a β-blocker at maximum tolerated dose, and who are in sinus rhythm (SR) with an HR of 70 beats/minute or greater at rest (class IIa recommendation). ii. Benefits (a) Decreased composite endpoint of CV death or hospitalization for HF (18% relative risk reduction compared with placebo) (b) Decreased hospitalization for HF (26% relative risk reduction compared with placebo) (c) Notable clinical trial: SHIFT iii. Mechanism of action: Selectively inhibits the If current in the sinoatrial node, providing HR reduction ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-84 Chronic Care in Cardiology k. iv. Dosing and administration considerations (a) Given the well-proven mortality benefits of β-blocker therapy, patients should be receiving β-blockers at maximally tolerated or target doses or have a contraindication to β-blocker therapy before assessing the resting HR for consideration of ivabradine initiation. (b) Initial dosing: Age younger than 75: 5 mg twice daily with food; age 75 and older: 2.5 mg twice daily with food (c) After 2–4 weeks, adjust dose according to HR: (1) Resting HR greater than 60 beats/minute: Increase dose by 2.5 mg twice daily until reaching the maximum dose of 7.5 mg twice daily. (2) Resting HR 50–60 beats/minute: Continue current dose. (3) Resting HR less than 50 beats/minute or signs/symptoms of bradycardia: Decrease dose by 2.5 mg twice daily or discontinue if already at 2.5 mg twice daily. (d) Maximum dose: 7.5 mg twice daily (e) Contraindications: ADHF, BP <90/50 mm Hg, resting HR <60 beats/min, sinoatrial block, concomitant use with strong CYP3A4 inhibitors, severe hepatic impairment (Child-Pugh class C) v. Monitoring (a) Assess HR and rhythm for bradycardia (6%–10%) and AF (5%–8%) after 2 weeks of therapy initiation or modification and periodically thereafter (b) Phosphenes (3%): transient rings or spots of light in the visual field Digoxin i. Place in therapy: Can be beneficial in decreasing hospitalizations in patients with HFrEF (class IIa indication); should be added after guideline-directed medical therapy ii. Benefits (a) Improved symptoms (b) Improved exercise tolerance (c) Decreased hospitalizations (28% relative risk reduction compared with placebo) (d) No effect on mortality (e) Notable clinical trial: DIG iii. Mechanism of action (in HF) (a) Inhibits myocardial Na-K adenosine triphosphatase (b) Decreases central sympathetic outflow by sensitizing cardiac baroreceptors (c) Decreases renal reabsorption of Na (d) Minimal increase in cardiac contractility iv. Dosing and administration considerations (a) For most patients, 0.125 mg/day is adequate to achieve the desired serum concentration. (b) Consider dosing 0.125 mg every other day in patients older than 70 years, those with impaired renal function, or those with low lean body mass. (c) No indication to load patients with digoxin in the setting of HF (d) Avoid abrupt discontinuation; can precipitate clinical deterioration (e) Drug interactions: Digoxin concentrations are increased with concomitant: (1) Clarithromycin, erythromycin (2) Amiodarone (reduce digoxin dose by 30%–50% or reduce dosing frequency) (3) Dronedarone (reduce digoxin dose by 50%) (4) Itraconazole, posaconazole (5) Cyclosporine, tacrolimus (6) Verapamil ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-85 Chronic Care in Cardiology v. Monitoring (a) Serum concentrations should be less than 1 ng/mL; in general, concentrations of 0.5–0.9 ng/mL are suggested. Serum concentrations should be obtained as a trough or at least 6–8 hours after the last dose. (1) Minimizes the risk of adverse effects and ventricular arrhythmias associated with increased concentrations. (2) Risk of toxicity increases with age and renal impairment. (3) Risk of toxicity increases in the presence of hypokalemia, hypomagnesemia, or hypercalcemia. (4) Signs of toxicity generally include nausea, vomiting, vision changes. (b) SCr should be monitored because the drug is primarily cleared renally. l. Vericiguat i. Place in therapy: May be considered in addition to optimized HF therapy to reduce HF hospitalizations and CV death in patients at high risk with worsening HFrEF ii. Benefits: Reduced the composite of death from CV causes or first hospitalization for HF compared with placebo in patients with NYHA class II–IV HF with LVEF less than 45% iii. Mechanism of action: Soluble guanylate cyclase stimulator that enhances production of cyclic guanosine monophosphate and enhances sensitivity to endogenous nitric oxide, resulting in smooth muscle relaxation and vasodilation iv. Dosing and administration considerations: (a) Initiate at 2.5 mg orally once daily and titrate to a target of 10 mg orally once daily. (b) Take with food. v. Monitoring: Monitor for hypotension and syncope. m. Polyunsaturated fatty acids (PUFAs) i. Place in therapy: Reasonable adjunctive therapy to reduce mortality and CV hospitalizations (class 2b recommendation). Both icosapent ethyl, a highly purified eicosapentaenoic acid (EPA), and combined EPA/docosahexaenoic acid (DHA) are included in the guidelines. ii. Benefits: In clinical trials, reduced the risk of death or hospital admission for CV event iii. Mechanism of action: Reduce production of very-low-density lipoproteins. The exact mechanisms resulting in CV outcome benefits remain unknown. iv. Dosing and administration considerations (a) Icosapent ethyl: 2 g orally twice daily (b) EPA/DHA formulations: 1000 mg of omega-3 PUFA orally daily (850 mg of EPA and 882 mg of DHA) (c) Take either formulation with food. v. Monitoring (a) Bleeding events (b) A dose-related risk of AF has been reported. n. Potassium binders i. Place in therapy: May be considered to improve outcomes in patients who experience hyperkalemia (K 5.5 mEq/L or greater) while taking a renin-angiotensin-aldosterone inhibitor (class 2b recommendation). Patiromer and sodium zirconium cyclosilicate are the agents included in the 2022 AHA/ACC/HFSA guidelines. ii. Benefits (a) In clinical trials, potassium binders resulted in lower potassium concentrations and less hyperkalemia. (b) Patiromer has been shown to increase the number of patients able to increase spironolactone dose to 50 mg compared with placebo. (c) Clinical benefits have not yet been established. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-86 Chronic Care in Cardiology 2. iii. Mechanism of action (a) Patiromer exchanges calcium for potassium in the GI tract, increasing potassium excretion. (b) Sodium zirconium cyclosilicate exchanges sodium and hydrogen for potassium in the GI tract, increasing potassium excretion. iv. Dosing and administration considerations (a) Patiromer (1) Powder for reconstitution that may be mixed with water, other beverages, or soft foods like applesauce or pudding (2) Administer other oral medications at least 3 hours before or after patiromer. (b) Sodium zirconium cyclosilicate (1) Powder for reconstitution that should be mixed with at least 3 tablespoons of water before administration (2) Administer other oral medications at least 2 hours before or after sodium zirconium cyclosilicate. v. Monitoring (a) Patiromer: Monitor for hypomagnesemia. (b) Sodium zirconium cyclosilicate: Monitor for edema. o. Other medication therapies i. Anticoagulation (a) Recommended for HF with permanent, persistent, or paroxysmal AF with an additional risk factor for stroke (no preference on agent) (b) Reasonable for patients with HF who have permanent, persistent, or paroxysmal AF without an additional risk factor for stroke (c) Not recommended in the absence of AF, prior stroke, or a cardioembolic source ii. Statins: Not recommended solely on the basis of HF diagnosis iii. A ntiarrhythmics: Given the neutral effects on mortality, the preferred antiarrhythmics in patients with HFrEF are dofetilide (AF/atrial flutter) and amiodarone. iv. Nondihydropyridine (DHP) calcium channel blockers (CCBs) with negative inotropic effects can be harmful in patients with a low EF and should be avoided (class III recommendation: harm). v. DHP CCBs: DHP CCBs have no proven benefit on morbidity or mortality in HF. Use of amlodipine can be considered for HTN or ischemic heart disease management in HF patients because of its neutral effects on morbidity and mortality. p. Device therapy i. Implantable cardioverter defibrillator recommended for primary prevention of sudden cardiac death in the following patients with ischemic or nonischemic HFrEF: (a) Patients with ischemic or nonischemic HFrEF (LVEF of 35% of less) and NYHA class II or III symptoms on chronic optimal medical therapy. Life expectancy should be greater than 1 year, and patient must be at least 40 days post-MI (class I indication). (b) Patients with HFrEF (LVEF of 30% or less) resulting from previous MI and NYHA class I symptoms on chronic optimal medical therapy. Life expectancy should be greater than 1 year, and patient should be at least 40 days post-MI (class I indication). ii. Chronic resynchronization therapy recommended for those with an LVEF of 35% or less, in SR, and a left bundle branch block with a QRS of 150 milliseconds or greater on optimal medical therapy with NYHA class II–III symptoms or NYHA class IV with ambulation Nonpharmacologic therapy a. Prevent further cardiac injury. i. Discontinue smoking. ii. Reduce weight if obese. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-87 Chronic Care in Cardiology b. c. d. e. f. g. iii. C  ontrol HTN (goal BP < 130/80 mm Hg per the 2017 ACC/AHA/Heart Failure Society of America Focused Update of the HF guidelines) iv. Control DM. v. Decrease alcohol intake to 2 or fewer drinks per day for men and 1 or fewer drinks per day for women. Eliminate alcohol intake if cardiomyopathy is alcohol induced. vi. Limit Na intake to 1500 mg/day for stages A and B; consider less than 3 g/day for stages C and D. vii. Treat sleep apnea. viii. Educate patient about appropriate self-care. Restricting fluid intake to 1.5–2 L/day is reasonable in stage D if serum Na is low. Modest exercise program benefits i. Possible modest effects on all-cause hospitalization and all-cause mortality, CV death or CV hospitalization, and CV death or HF hospitalization ii. Safe for patients with HF Influenza and pneumococcal vaccines Monitor and appropriately replace electrolytes (to minimize risk of arrhythmias). Monitor for thyroid disease. i. Hypothyroidism can be masked by HF symptoms. ii. Hyperthyroidism will worsen systolic dysfunction. Screen for and treat depression. Patient Case 3. W hich drug that J.T. (from Patient Case 2) is currently taking would be best to discontinue because of his HFrEF? A. Acetaminophen. B. Sertraline. C. Cilostazol. D. Levothyroxine. C. HFpEF: Clinical evidence for efficacious agents for HFpEF has generally been disappointing. Therapies for symptoms, comorbidities, and risk factors that can worsen CV disease are recommended. 1. SBP and diastolic blood pressure (DBP) should be well controlled (class 1 recommendation). HTN impairs myocardial relaxation and promotes cardiac hypertrophy. 2. Diuretics should be used for symptom relief in volume overload. 3. SGLT2 inhibitors can be beneficial to decrease HF hospitalizations and CV mortality (class 2a recommendation). 4. MRAs and ARNIs or ARBs may be considered to decrease HF hospitalizations, particularly among patients with LVEF on the lower end of the spectrum (class 2b recommendations). 5. Management of AF can be useful to improve symptomatic HF (class 2a recommendation). D. HF with Mildly Reduced EF (HFmrEF) 1. Defined as HF with an LVEF of 41%–49% and evidence of spontaneous or provokable increased LV filling pressures (e.g., elevated natriuretic peptides, hemodynamic measurements) 2. Pharmacologic recommendations a. In patients with current or previous symptoms, use of an ARNI, ACE inhibitor, or ARB; MRA; and metoprolol succinate, carvedilol, or bisoprolol may be considered to reduce CV mortality and HF hospitalizations, particularly among patients with LVEF on the lower end of the spectrum (class 2b recommendation). ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-88