Chronic Care in Cardiology PDF

Chronic Care in Cardiology b.  GLT2 inhibitors can be beneficial for decreasing CV mortality and HF hospitalizations (class 2a S recommendation). E. H  FimpEF: HF with improved LVEF is defined as a documented LVEF of less than 40% at baseline plus a documented LVEF improvement of 10% or greater...

Chronic Care in Cardiology b.  GLT2 inhibitors can be beneficial for decreasing CV mortality and HF hospitalizations (class 2a S recommendation). E. H  FimpEF: HF with improved LVEF is defined as a documented LVEF of less than 40% at baseline plus a documented LVEF improvement of 10% or greater and a second LVEF measurement of greater than 40%. 1. HFimpEF is distinct from both HFrEF and HFpEF because of distinct biology and improved outcomes compared with the other two causes. 2. Guideline-directed medical therapy should not be discontinued in HFimpEF; discontinuation may cause HF recurrence. F.  edications That Cause/Exacerbate HF: An AHA scientific statement addresses medications that can cause M or exacerbate HF. Drugs to avoid or use with caution in HF include: 1. Drugs that promote sodium and water retention a. Nonsteroidal anti-inflammatory drugs (NSAIDs, including selective cyclooxygenase-2 inhibitors) i. Promote Na and water retention ii. Blunt diuretic response iii. Increase morbidity and mortality b. Corticosteroids c. Minoxidil d. Thiazolidinediones 2. Drugs with negative inotropic effects a. Class I and III antiarrhythmic agents (except for amiodarone and dofetilide) i. Also have proarrhythmic effects ii. Amiodarone and dofetilide are safe in patients with HF. iii. Avoid dronedarone; it is contraindicated in patients with symptomatic HF with recent decompensation necessitating hospitalization or NYHA class IV HF. b. CCBs (except for amlodipine and felodipine) i. Also promote neurohormonal activation ii. Amlodipine and felodipine have been proven safe in patients with HF and can be added when additional BP reduction is needed; monitor for edema. c. Cilostazol d. Itraconazole 3. Other a. Metformin: Increased risk of lactic acidosis (black box warning) b. Saxagliptin and alogliptin: Associated with increased risk of hospitalization c. Amphetamines (e.g., methylphenidate) i. α- and β-agonist activity ii. Cause tachycardia iii. Proarrhythmic effects d. Pregabalin i. Inhibits calcium channels ii. Lower-extremity edema, HF exacerbation e. Nutritional supplements i. Lack of evidence ii. Lack of product regulation iii. Potential for drug interactions and/or increased risk of bleeding ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-89 AL GRAWANY Chronic Care in Cardiology II. ATRIAL FIBRILLATION A. Background 1. Prevalence a. Most common arrhythmia: 2.2 million Americans b. Prevalence increases with age. c. Common comorbidity in patients with valvular heart disease or HF 2. Signs and symptoms a. Some patients have no symptoms. b. Potential symptoms that may be present to some degree include the following: i. Palpitations ii. Chest pain iii. Dyspnea iv. Fatigue v. Lightheadedness c. Rare cases of thromboembolic events d. Symptoms vary with ventricular rate, underlying LVEF, AF duration, and individual patient perceptions. 3. Classification a. Paroxysmal: Spontaneous self-termination within 7 days of onset b. Persistent: Lasting more than 7 days c. Long-standing persistent: Continuous duration of more than 12 months d. Permanent: Present all the time, unable to return to SR using pharmacologic or nonpharmacologic options e. Nonvalvular: The absence of moderate-severe mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair Patient Case 4. P.M. is a 52-year-old man (height 70 inches, weight 116 kg) with a history of HTN and a transient ischemic attack 2 years ago. He visits his primary care doctor with the chief concern of several weeks of a “fluttering” feeling in his chest on occasion. He thinks the fluttering is nothing; however, his wife insists he have it checked. His current medications include metoprolol tartrate 50 mg twice daily and aspirin 81 mg/day. He is adherent to this regimen and has health insurance, but he does not like to make the 3-hour trip to his primary care provider. His laboratory data from his past visit were all within normal limits. His vital signs today include BP 130/78 mm Hg and HR 76 beats/minute. All laboratory values are within normal limits. An electrocardiogram (ECG) reveals an irregularly irregular rhythm, with no P waves, and a HR of 74 beats/minute. A diagnosis of AF is made. What is the best approach for managing his AF at this time? A. Begin digoxin 0.25 mg/day. B. Begin diltiazem CD 240 mg/day. C. Begin warfarin 5 mg/day and titrate to a goal INR of 2.5. D. Begin dabigatran 150 mg twice daily. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-90 Chronic Care in Cardiology B. Pathophysiology 1. Cardiac conduction in a normal heart and a heart with atrial fibrillation (Figure 2) His The impulse: 1. Is generated by the SA node. 2. Propagates through atrial tissue. 3. Reaches the AV node. 4. Passes slowly through the AV node. 5. Travels through the bundle of His. 6. Is conducted simultaneously down the three bundle branches. 7. Is distributed to the ventricular tissue by small embedded Purkinje fibers. Figure 2. Cardiac conduction and atrial fibrillation. The impulses: 1. A re generated in atrial tissues; ± focal activation, with reentry pathways 2. Bombard the AV node in a rapid and chaotic fashion. 3. A re propagated by the AV node after it repolarizes from the last impulse. 4. See 5–7 above. Figure 2. Cardiac conduction and atrial fibrillation. (continued) AV = atrioventricular; SA = sinoatrial. 2. ECG findings Figure 3. Electrocardiogram showing atrial fibrillation. 3. AF causes (Table 7). ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-91 Chronic Care in Cardiology Table 7. Potential Causes of AF Atrial Distension Chronic hypertension Mitral valve disease Cardiomyopathy Congenital defects Pulmonary hypertension Acute pulmonary embolus Myocardial ischemia Sleep apnea Emphysema or other lung diseases High Adrenergic Tone Alcohol withdrawal Thyrotoxicosis Sepsis Binge drinking Surgery Sympathomimetics such as cocaine or amphetamines Excessive theophylline, caffeine C. Pharmacologic therapy 1. Ventricular rate control a. If patients have a rapid ventricular rate, AV nodal blockade is necessary. b. Goal HR (resting HR less than 80 beats/minute) is reasonable in symptomatic patients (class IIa recommendation). A more lenient rate control (resting HR less than 110 beats/minute) may be reasonable in patients who are asymptomatic and have preserved ejection fraction (class IIb recommendation). c. The goal is to reduce symptoms and possibly prevent tachycardia-induced cardiomyopathy. d. Select the best agent according to individual clinical response and concomitant disease states. i. β-Blockers (a) Any agent with β-blockade can be used and dosed to the goal HR. (b) Labetalol or carvedilol if additional α1-blockade is desirable (e.g., HTN) (c) β-Blockers may be preferred in patients with a history of MI. (d) Select carvedilol, metoprolol succinate, or bisoprolol in patients with HFrEF (e) Avoid in patients with Wolff-Parkinson-White syndrome (f) Effective for controlling exercise-associated HR increases ii. Non-DHP CCBs: Verapamil or diltiazem (a) Avoid use if there is concomitant left ventricular systolic dysfunction. (b) May be preferred over β-blocker in patients with asthma or severe chronic obstructive pulmonary disease (c) Effective for controlling exercise-associated HR increases (d) Avoid in patients with Wolff-Parkinson-White syndrome iii. Digoxin (a) Often ineffective alone for controlling ventricular rate in AF, especially during exercise or movement (because of minimal effectiveness with sympathetic stimulation) (b) Not usually first-line therapy, especially when rapid rate control is desired (2014 AHA AF guidelines) (c) Can be included in regimen if patient has HFrEF (d) May be effective if additional HR control is needed when a patient is already receiving a β-blocker, diltiazem, or verapamil (e) Avoid in patients with Wolff-Parkinson-White syndrome (f) May be agent of choice if patient has uncontrolled HR and decompensated HF iv. Amiodarone (a) May be used for rate control in patients with HF who do not have an accessory pathway (b) May be used for rate control in patients who are refractory to other therapies such as β-blockers, non-DHP CCBs, and digoxin ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-92 Chronic Care in Cardiology 2. Rhythm control: a. W hen to choose a rhythm-control approach i. Historically, maintaining SR offered no advantage over ventricular rate control and was associated with more hospitalizations (AFFIRM trial). ii. However, specific patients may benefit from a rhythm-control approach: (a) Patients with intractable and intolerable symptoms such as dyspnea, palpitations, and exercise intolerance) despite adequate rate control (b) Patients in whom adequate ventricular rate control cannot be achieved iii. The recent EAST-AFNET 4 trial found rhythm control (with antiarrhythmics, cardioversion, or ablation) superior to rate control in reducing adverse CV outcomes among patients with a recent (less than 12 months prior) diagnosis of AF and concomitant CV conditions. iv. The most recent AF guidelines were published before release of the EAST-AFNET 4 trial. Currently, it is reasonable to select an initial rhythm-control approach in selected patients with a recent (less than 12 months prior) diagnosis of AF and additional CV risk factors. Table 8. Summary of the Pros and Cons of Rate Control vs. Rhythm Control Pros Generally easy to achieve and maintain; out-of-hospital therapy typical Rate control strategy Rhythm control strategy If patient is symptomatic with fatigue and exercise intolerance, these symptoms may improve if SR is attained (especially in patients with HF); minimizes development of structural atrial changes; acceptable for all age groups Cons Electrical and structural remodeling because of continued AF makes future attainment of SR virtually impossible; safety not proven for younger patients Adverse effects of antiarrhythmic medications; cost of medications and monitoring; likelihood of AF recurrence; in-hospital stay may be necessary to initiate therapy AF = atrial fibrillation; HF = heart failure; SR = sinus rhythm. b. Cardioversion in AF i. If cardioversion is attempted (electric or pharmacologic), the absence of atrial thrombi must be ensured. ii. Without anticoagulation (thrombi caused by decreased or stagnant blood flow in the atria) (a) AF for more than 48 hours = 15% rate of atrial thrombus. (b) AF for more than 72 hours = 30% rate of atrial thrombus. iii. Thrombi present plus cardioversion = 91% stroke rate. iv. Ensure safe cardioversion by either: (a) Transesophageal echocardiogram (TEE) to visualize the atria, or (b) Three or more weeks of therapeutic anticoagulation (1) INR 2.0-3.0 if warfarin is selected (2) Direct oral anticoagulants (DOACs) may also be used v. Continue anticoagulation for at least four weeks after cardioversion with either: (a) Warfarin or (b) A DOAC ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-93 Chronic Care in Cardiology vi. Specific recommendations for anticoagulation are described in Table 9. Table 9. Anticoagulation Strategies Surrounding Cardioversion of AFa AF Type Unstable AF Stable AF, duration <48 hrb Stable AF, duration unknown or >48 hr (no TEE) Stable AF, duration unknown or >48 hr (with TEE-guided cardioversion) Anticoagulation Recommendations • Synchronized cardioversion; anticoagulate immediately beforehand with parenteral therapy • A nticoagulate for ≥4 wk after cardioversion with warfarin or a DOAC if AF ≥ 48 hr or if duration is unknown ACCP (CHEST) guidelines: • A nticoagulate at presentation and continue through cardioversion – LMWH or UFH at full treatment doses • A nticoagulate for ≥4 wk afterward, regardless of baseline risk of stroke ACC/AHA/HRS AF guidelines: • A nticoagulation as soon as possible before cardioversion is recommended with a CHA 2DS2-VASc score of ≥2 (men) or ≥3 (women); anticoagulation may be considered with a score of 0-1 (men) or 1-2 (women) – UFH, LMWH, or DOAC • Need for anticoagulation after cardioversion should be based on the patient’s risk of thromboembolism, according to their CHA 2DS2-VASc score ACCP (CHEST) guidelines: • A nticoagulate for 3 wk before cardioversion – Warfarin with INR 2.0–3.0 or a DOAC • A nticoagulate for ≥4 wk afterward, regardless of baseline risk of stroke ACC/AHA/HRS AF guidelines: • A nticoagulate for ≥3 wk before cardioversion – Warfarin with INR 2.0–3.0 2.0-3.0 or DOAC, dabigatran, rivaroxaban, apixaban, or enoxaparin (full treatment doses) • A nticoagulate for 4 wk after cardioversion, regardless of CHA2DS2-VASc score ACCP (CHEST) guidelines: • TEE-guided therapy with abbreviated anticoagulation before cardioversion – LMWH or UFH at full treatment doses should be initiated at the time of TEE, and cardioversion should be performed within 24 hr of TEE if no thrombus is seen • A nticoagulate for ≥4 wk after cardioversion, regardless of baseline risk of stroke ACC/AHA/HRS AF guidelines: • If no identifiable thrombus seen on TEE, cardioversion is reasonable, provided anticoagulation is achieved before TEE • If thrombus identified on TEE, 3 wk of therapeutic anticoagulation is required before cardioversion • A nticoagulation should be maintained after cardioversion for ≥4 wk Potential risk of cardioversion with antiarrhythmic drugs should be considered before treatment initiation. No randomized trials have compared different anticoagulation strategies in patients with AF < 48 hr. ACC = American College of Cardiology; ACCP = American College of Chest Physicians; AF = atrial fibrillation; AHA = American Heart Association; DOAC = direct oral anticoagulant; HRS = Heart Rhythm Society; INR = international normalized ratio; LMWH = low-molecularweight heparin; TEE = transesophageal echocardiography; UFH = unfractionated heparin. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2019;140:e125-151; Lip GY, Banerjee A, Boriani G, et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest 2018;151:1121-201. a b ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-94 Chronic Care in Cardiology c. Oral antiarrhythmic agents to induce or maintain SR (class Ic and class III agents are recommended in atrial fibrillation; choice of agent depends on patient comorbidities) i. Class Ic antiarrhythmics: 80% - 90% efficacy (a) Flecainide and propafenone can be considered first-line therapies for patients without structural heart disease (Figure 4). Propafenone also displays some nonselective β-blocking properties. (b) Concomitant AV nodal blocking agent (e.g., β-blocker or non-DHP CCB) typically required (c) Contraindicated in patients with structural heart disease (including CHD, HF, left ventricular hypertrophy, and valvular heart disease) ii. Class III antiarrhythmics (a) Amiodarone: 85%–95% efficacy (1) Has electrophysiologic properties of classes I–IV (2) Oral loading dose required (e.g., 400 mg 2 or 3 times per day for 2 weeks and then 400 mg/day for 4 weeks, followed by a 200-mg/day maintenance dose). Achieving a loading dose of 10 g is desirable. Many different regimens exist. (3) Long half-life of about 60 days (4) In addition, has AV nodal blocking properties, which may help to control HR if AF recurs (5) May use in patients with HF (6) Hepatically metabolized: Cytochrome P450 (CYP) 3A4 substrate; inhibitor of CYP3A4, CYP1A2, CYP2C9, CYP2D6, and P-glycoprotein (P-gp) (7) Minimal incidence of ventricular arrhythmias (8) Drug interactions (many) (A) Digoxin: Increased digoxin exposure. Lower digoxin dose by 50%. (B) Warfarin: Increased warfarin exposure. Lower warfarin dose by 33%–50%. (C) Simvastatin: Increased simvastatin exposure. Do not exceed dose of 20 mg/day. (D) Lovastatin: Increased lovastatin exposure. Do not exceed dose of 40 mg/day. (E) β-Blockers, non-DHP CCBs, clonidine, ivabradine: Additive bradycardia (9) Extensive monitoring for noncardiac adverse effects (A) Liver function tests (LFTs): Baseline and every 6 months (B) Thyroid function tests: Baseline and every 6 months (C) Chest radiography: Baseline and annually (D) ECG: Periodically (E) Pulmonary function tests (including DLCO [carbon dioxide diffusion in the lungs]): Baseline and for unexplained cough/dyspnea, chest radiographic abnormalities or clinical suspicion. Discontinue if pulmonary fibrosis occurs. (F) Ophthalmologic examination: Baseline (if visual impairment) and if patient has symptoms of visual impairment. Discontinue if optic neuritis occurs. (G) Skin toxicities: “Blue skin” syndrome and sunburn (H) Neurologic toxicity: Tremor, neuropathy (I) Nausea, vomiting (J) Adverse effects may require increased monitoring, dose reduction, or drug discontinuation (b) Sotalol: 50%–60% efficacy (1) Renal excretion. Dose adjustment and vigilant corrected QT (QTc) interval monitoring necessary in renal impairment. Recommended starting dose is 80 mg twice daily (unless creatinine clearance [CrCl] less than 60 mL/minute, then once daily). (2) Should be initiated in the hospital (minimum of 3-day stay), where QTc interval, serum electrolytes (e.g., K and magnesium), and renal function can be monitored ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-95 Chronic Care in Cardiology (3) C  ontraindicated in patients with HF (stable or unstable); CrCl less than 40 mL/minute; QTc interval greater than 450 milliseconds; and second- or third-degree AV block or sick sinus syndrome (in absence of pacemaker) (4) Possesses nonselective β-blocking properties; may result in additive bradycardia with β-blockers, non-DHP CCBs, clonidine, ivabradine, and digoxin (5) Sotalol is ineffective for cardioversion but may be used for maintenance of NSR (normal SR). (c) Dofetilide: 50%–60% efficacy (1) Should be initiated in the hospital (minimum of 3-day stay) so that QTc interval, serum electrolytes (e.g., K and magnesium), and renal function can be monitored (2) Starting dose is selected based on renal function (A) CrCl greater than 60 mL/minute: 500 mcg twice daily (B) CrCl 40–60 mL/minute: 250 mcg twice daily (C) CrCl 20–39 mL/minute: 125 mcg twice daily (D) CrCl less than 20 mL/minute: Contraindicated (3) Modification of subsequent doses is based on QTc interval measured 2–3 hours after initial dose: QTc > 500 milliseconds (or 550 milliseconds in ventricular conduction abnormalities) OR QTc increased greater than 15% above baseline: reduce dose by 50% (4) If QTc is greater than 500 milliseconds (or 550 milliseconds in ventricular conduction abnormalities) at any point after in-hospital doses 2–5, discontinue dofetilide (5) Hepatically metabolized by CYP3A4 (6) Renal elimination through renal cationic secretion; check QTc interval if renal function declines (7) Contraindicated in patients with CrCl less than 20 mL/minute or QTc interval greater than 440 milliseconds (or 500 milliseconds for patients with ventricular conduction abnormalities) (8) May use in patients with HF (9) Drug interactions (A) Avoid concomitant use of the following drugs: cimetidine, verapamil, itraconazole, ketoconazole, hydrochlorothiazide, prochlorperazine, megestrol, dolutegravir, and trimethoprim alone or in combination with sulfamethoxazole (B) Use CYP3A4 inhibitors, triamterene, metformin, and amiloride with caution: increased dofetilide exposure (d) Dronedarone: 21%–25% efficacy (1) Amiodarone analog lacking the iodine moiety that contributes to the thyroid toxicity of amiodarone (2) Has electrophysiologic properties of classes I–IV (3) Dose: 400 mg twice daily with morning and evening meal (4) Hepatically metabolized; CYP3A4 substrate; CYP3A4, CYP2D6, and P-gp inhibitor (5) Half-life is 13–19 hours. (6) Small increase in SCr by 0.1 mg/dL probably a result of inhibition of creatinine’s tubular secretion; rapid onset, will plateau after 7 days, and is reversible. Monitor SCr periodically. (7) Acute kidney injury has also been reported, and it is usually reversible with drug discontinuation. (8) Contraindicated in permanent AF; NYHA class II or III HF with recent decompensation necessitating hospitalization; NYHA class IV HF; second- or third-degree AV block or sick sinus syndrome (in absence of pacemaker); severe liver impairment, HR less than 50 beats/minute; concurrent use of strong CYP3A4 inhibitors or QTc interval–prolonging agents; history of amiodarone-induced hepatotoxicity or pulmonary toxicity; pregnancy; or QTc interval 500 milliseconds or greater ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-96 Chronic Care in Cardiology (9) O  ne trial found dronedarone less effective than amiodarone for the maintenance of SR, but with fewer adverse effects. (10) Drug interactions (A) Digoxin: Increased digoxin exposure; lower digoxin dose by 50% (B) β-Blockers, non-DHP CCBs, and clonidine: Excessive bradycardia; initiate these drugs at lowest dose. Diltiazem and verapamil can increase dronedarone exposure; therefore, monitor ECG. (C) Statins: Increased statin exposure. Limit dose of simvastatin to 10 mg/day and lovastatin to 20 mg/day. (D) Dabigatran: In patients with moderate renal impairment (CrCl 30–50 mL/minute), dronedarone increases dabigatran exposure; decrease dabigatran dose to 75 mg twice daily. (E) Strong CYP3A4 inhibitors and inducers: Avoid. (F) Cyclosporine, tacrolimus, sirolimus: Increased exposure of these agents; monitor serum concentrations closely (11) Other safety issues (A) Liver injury: According to postmarketing surveillance, dronedarone has been associated with rare but severe hepatic liver injury. Hepatic enzymes should be monitored, especially during the first 6 months of treatment. (B) Pulmonary toxicity: In postmarketing surveillance, cases of interstitial lung disease, including pneumonitis and pulmonary fibrosis, have been reported. Patients should report any new signs of dyspnea or nonproductive cough. No Structural Heart Disease Structural Heart Disease a CHD HF a Dofetilideb,c Dronedarone Flecainideb,d Propafenoneb,d Sotalolb,c Amiodarone Catheter ablatione Dofetilideb,c Dronedarone Sotalolb,c Catheter ablatione Amiodarone Dofetilideb,c Amiodarone Figure 4. Options for rhythm control in patients with paroxysmal and persistent atrial fibrillation. Antiarrhythmics are listed in alphabetical order and not order of preference Depends on patient preference when performed in experienced centers. Not recommended with severe left ventricular hypertrophy (wall thickness > 1.5 cm). c Use with caution in patients at risk of torsades de pointes ventricular tachycardia. d Should be combined with atrioventricular nodal blocking agents. e Catheter ablation is only recommended as first-line therapy for patients with paroxysmal atrial fibrillation (class IIa recommendation). CHD = coronary heart disease; HF = heart failure. Adapted with permission from: January CT, Wann SL, Sacco RL, et al. AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and Heart Rhythm Society. Circulation 2014;130:2071. a b ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-97 Chronic Care in Cardiology 3. Antithrombotic therapy a. The average annual stroke rate is 5% per year without anticoagulation. i. A patient’s individual risk can vary from about 1% to 20% per year depending on risk factors. ii. This risk is independent of current cardiac status (i.e., SR or AF). b. Risk stratification and treatment determination is based on the CHA2DS2-VASc score (Tables 10–11). Of note, the 2018 CHEST guidelines for anticoagulation in atrial fibrillation no longer recommend antiplatelet therapy alone for prevention of stroke or systemic embolism. Table 10. Risk Stratification for Antithrombotic Therapy Using the CHA2DS2-VASc Scorea Risk Factor CHF or LVEF ≤ 40% Hypertension Age ≥ 75 yr Diabetes Stroke, TIA, thromboembolism Vascular disease Age 65–74 yr Sex category (female) Score 1 1 2 1 2 1 1 1 For use in patients with nonvalvular atrial fibrillation. Maximum point value is 9. CHF = congestive heart failure; LVEF = left ventricular ejection fraction; TIA = transient ischemic attack. a Table 11. AHA/ACC/HRS Guideline Recommendations for Antithrombotic Therapy in Patients with Nonvalvular Atrial Fibrillation per CHA2DS2-VASc Score CHA2DS2-VASc Score = 0 in Men or 1 in Women Reasonable to omit anticoagulant therapy CHA2DS2-VASc Score = 1 in men or 2 in women May consider oral anticoagulation CHA2DS2-VASc Score = 2 in men or 3 in women Oral anticoagulant therapy is indicated. DOAC over warfarin in patients eligible for DOACsa Exclusions include moderate to severe mitral stenosis or mechanical heart valve. DOAC = direct oral anticoagulant. a Patient Case 5. H.D. is a 67-year-old man with a history of HTN and AF for 4 years. His medications include ramipril 5 mg twice daily, sotalol 120 mg twice daily, digoxin 0.125 mg/day, and warfarin 5 mg/day. He visits his primary care physician today after being discharged from the emergency department with increased fatigue on exertion, palpitations, and lower extremity edema. His vital signs today include BP 115/70 mm Hg and HR 88 beats/minute, and all laboratory results are within normal limits; however, his lower extremity edema has worsened. His INR is 2.8. His ECG shows AF. An echocardiogram reveals an LVEF of 35%–40%. H.D.’s physician would like to continue a rhythm control approach. What is the best treatment option for managing his AF? A. Discontinue sotalol and begin metoprolol succinate 12.5 mg/day. B. Discontinue sotalol and begin dronedarone 400 mg twice daily. C. D  iscontinue sotalol and begin amiodarone 400 mg twice daily, tapering to goal dose of 200 mg/day for the next 6 weeks. D. Continue sotalol and add metoprolol tartrate 25 mg twice daily. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-98 Chronic Care in Cardiology D. Nonpharmacologic therapies (procedures) 1. Electrical cardioversion (low-energy cardioversion; sedation highly desirable) 2. AV nodal ablation: Ablate AV node and chronically pace the ventricles. 3. Pulmonary vein ablation: Ablates the origin of the abnormal atrial foci, which is often near the pulmonary vein–atrial tissue intersection. III. HYPERTENSION Definition: HTN is a persistent, nonphysiologic elevation of BP; it is defined as an SBP of 130 mm Hg or greater and/or a DBP of 80 mm Hg or greater. A. Background 1. Prevalence a. Most common chronic disease in the United States b. Affects 46% of the population c. Prevalence increases with age d. Major modifiable risk factor for CV disease and stroke 2. Etiology a. Essential HTN: 90% (no identifiable cause) i. Obesity is a contributor ii. Evaluate Na intake b. Secondary HTN i. Primary aldosteronism ii. Renal parenchymal disease iii. Renal artery stenosis iv. Obstructive sleep apnea v. Cushing syndrome vi. Thyroid or parathyroid disease vii. Medications (e.g., cyclosporine, NSAIDs, sympathomimetics) viii. Pheochromocytoma 3. Diagnosis a. Periodic screening for all people older than 18 years b. Patient should be seated quietly in chair for at least 5 minutes. c. Use appropriate cuff size (bladder length at least 80% the circumference of the arm). d. Take BP at least twice, separated by at least 2 minutes. e. The average BP on two separate visits is required to diagnose HTN accurately. f. Home blood pressure monitoring (HBPM) and ambulatory blood pressure monitoring (ABPM) are recommended to confirm diagnosis, screen for white-coat HTN, and screen for masked HTN i. White-coat HTN: Office blood pressure is 130/80-160/100 mm Hg after a 3-month trial of lifestyle modification but with daytime ABPM or HBPM blood pressure less than 130/80 mm Hg ii. Masked HTN: Office blood pressure is 120-129/less than 80 mm Hg after a 3-month trial of lifestyle modification; daytime ABPM or HBPM blood pressure of 130/80 or greater 4. Benefits of treating elevated BP a. Decreased risk of stroke (by 35-40%) b. Decreased risk of MI (by 20-25%) c. Decreased risk of HF (by 50%) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-99 Chronic Care in Cardiology 5. Effects of lifestyle modifications on BP (Table 12) Table 12. Recommended Lifestyle Modifications Modification Weight reduction Recommendation Maintain a normal body weight (BMI 18.5–24.9 kg/m 2) Adopt DASH eating plan (includes substantial K intake) Reduce Na intake Consume a diet rich in fruits, vegetables, and low-fat dairy products with a reduced content of saturated and total fat Physical activity Moderation of alcohol consumption Approximate SBP Reduction 5–20 mm Hg per 10-kg weight loss 8–14 mm Hg Reduce Na intake to < 1500 mg/day 2–8 mm Hg Reducing Na intake by at least 1000 mg/day will lower BP if desired daily Na intake goal is not achieved Engage in regular aerobic physical activity such as brisk walking (at least 30 min/day most days of the week) Limit consumption to: 4–9 mm Hg 2–4 mm Hg Men: 2 drinks/day (24 oz of beer, 10 oz of wine, or 3 oz of 80-proof whiskey) Women and those of lower body weight: 1 drink/day BMI = body mass index; BP = blood pressure; DASH = Dietary Approaches to Stop Hypertension; Na = sodium; SBP = systolic blood pressure. B. Therapeutic management 1. Patient classification and management in adults (Table 13) Table 13. Classification of BP and Hypertension and Lifestyle Modification Recommendations BP Classification Normal Elevated SBP (mm Hg) DBP (mm Hg) < 120 < 80 and 120-129 < 80 and Stage 1 hypertension Stage 2 hypertension Hypertensive urgency/ emergency 130-139 ≥140 >180 or or or 80-89 ≥ 90 >120 BP = blood pressure; DBP = diastolic blood pressure; SBP = systolic blood pressure Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018;71:e127-248. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-100 Chronic Care in Cardiology 3. Blood pressure treatment strategies according to BP and ASCVD risk are located in Figure 5. Figure 5. BP treatment strategies according to BP level and ASCVD risk. *I nitiation of antihypertensive drug therapy with two first-line agents of different classes, either as separate agents or in a fixed-dose combination, is recommended in adults with stage 2 HTN and an average blood pressure of greater than 20/10 mm Hg above their blood pressure target. ASCVD = atherosclerotic cardiovascular disease; BP = blood pressure. Adapted from: McConnell KJ. Blood pressure management of adult patients. In: Baker WL, Beavers C, Bolesta S, et al., eds. ACCP/ASHP 2019 Cardiology Pharmacy Preparatory Review and Recertification Course, 2019. Lenexa, KS: American College of Clinical Pharmacy, 2019:95. 4. Select an appropriate drug therapy regimen a. Initiating therapy with a single antihypertensive drug is reasonable in adults with stage 1 HTN and a BP goal of less than 130/80 mm Hg b. Initiating antihypertensive drug therapy with two first-line agents of different classes is recommended in adults with stage 2 HTN and an average BP greater than 20/10 mm Hg above their BP target c. First-line agents include thiazide diuretics, CCBs, and ACE inhibitors or ARBs. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-102 Chronic Care in Cardiology d. First-line agents for patients with comorbidities is described in Figure 6. Initial medication choice based on disease state Diabetes CKD Stroke or TIA ACEI, ARB, CCB, or thiazide; ACEI/ARB preferred in albuminuria ACEI or ARB in patients with albuminuria Thiazide, ACEI, or ARB Coronary disease HFrEF HFpEF BB + ACEI or ARB ACEI, ARB, or ARNI; BB; AA; as needed diuretic Diuretic, ACEI, ARB, or BB Figure 6. Selecting appropriate therapy for hypertension on the basis of disease state. AA = aldosterone antagonist; ACEI = angiotensin-receptor converting enzyme inhibitor; ARB = angiotensin receptor blocker; ARNI = angiotensin receptor–neprilysin inhibitor; BB = β-blocker; CCB = calcium channel blocker; CKD = chronic kidney disease; HFpEF = heart failure with preserved ejection fraction; HFrEF = heart failure with reduced ejection fraction; TIA = transient ischemic attack. 5. Considerations with specific antihypertensive agents a. β-Blockers i. Evidence is insufficient to recommend β-blockers as initial therapy in patients without specific CV comorbidities. ii. Caution with asthma or severe chronic obstructive pulmonary disease (especially higher doses) because of pulmonary β-receptor blockade, especially with nonselective β-blockers or high-dose selective β-blockers. iii. Greater risk of developing DM than with an ACE inhibitor, ARB, and CCB; use caution in patients at high risk of DM (e.g., family history, obesity) iv. Can mask some signs of hypoglycemia in patients with DM v. Can cause depression b. Thiazides i. Can worsen gout by increasing serum uric acid ii. May have reduced efficacy in severely impaired renal function iii. Greater risk of developing DM than with ACE inhibitor, ARB, and CCB; use caution in patients at high risk of DM (e.g., family history, obesity) iv. Can assist in the management of osteoporosis by preventing urine calcium loss v. Monitor for hyponatremia and hypokalemia. c. ACE inhibitors and ARBs i. Contraindicated in pregnancy ii. Contraindicated with bilateral renal artery stenosis iii. Monitor K closely, especially if renal impairment exists or another K-sparing drug or K supplement is used. d. Direct renin antagonist (aliskiren) i. Avoid concurrent use with ACE inhibitors or ARBs in patients with renal impairment (CrCl less than 60 mL/minute). ii. Contraindicated in pregnancy ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-103 Chronic Care in Cardiology 6. 7. iii. C  ontraindicated in patients with DM when used in combination with ACE inhibitors or ARBs because of increased risk of renal impairment, hyperkalemia, and hypotension iv. Avoid use in combination with cyclosporine or itraconazole. e. Calcium channel blockers i. Dihydropyridine CCBs (a) Amlodipine, felodipine, nifedipine (b) Monitor for peripheral edema, reflex tachycardia, and orthostatic hypotension (c) Useful for isolated systolic hypertension or use in African American patients ii. Nondihydropyridine CCBs (a) Diltiazem, verapamil (b) Indicated in hypertensive patients with comorbid conditions which would benefit from HR reduction (e.g., atrial fibrillation, stable angina) (c) Contraindicated in heart block and sick sinus syndrome (d) Potential drug interactions due to CYP450 inhibition Considerations within specific patient populations a. Patients with CHD: Potent vasodilators (hydralazine, minoxidil, and DHP CCBs) may cause reflex tachycardia, thereby increasing myocardial oxygen demand; can attenuate this by also using an AV nodal blocker (β-blocker or non-DHP CCB) b. Older adult patients (65 and older): i. Treatment of HTN with an SBP treatment goal of less than 130 mm Hg is recommended for noninstitutionalized ambulatory community-dwelling adults with an average SBP of 130 mm Hg or greater ii. For older adults with HTN and a high burden of comorbidity and limited life expectancy, clinical judgment, patient preference, and a team-based approach to assess risk-benefit is reasonable for decisions regarding intensity of blood pressure lowering and choice of antihypertensives iii. The SPRINT trial published in late 2015 showed that targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major CV events and death from any cause among patients at high risk of CV events but without DM. Twenty-five percent of the study population was older than 75 years. iv. Caution with antihypertensive agents and orthostatic hypotension c. Black patients: β-Blockers and ACE inhibitors are generally less effective as monotherapy than in non–black patients. In black adults with HTN but without HF or CKD, including those with diabetes mellitus, initial antihypertensive treatment should include a thiazide-type diuretic or CCB. β-blockers and ACE inhibitors should still be used if comorbid conditions dictate. d. Women i. Oral estrogen-containing contraceptives can increase BP, and the risk can increase with the duration of use. ii. HTN increases the risk to mother and fetus in women who are pregnant. Preferred medications include methyldopa, nifedipine, and labetalol. ACE inhibitors, ARBs, and aliskiren should not be used because of the potential for fetal defects. Monitoring a. Have the patient return in 4 weeks to assess efficacy (sooner if clinically indicated). b. If there is an inadequate response with the first agent with optimal dosing (and adherence is verified) and no compelling indication exists, initiate therapy with a drug from a different class while continuing initial therapy. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-104 Chronic Care in Cardiology 8. Resistant HTN a. Confirm diagnosis i. Office BP of 130/80 mm Hg or greater and patient taking at least three antihypertensive medications at optimal doses, including a diuretic (confirmed adherence) OR ii. Office BP of <130/80 mm Hg but patient requires at least four antihypertensive medications b. Exclude pseudoresistance i. Ensure accurate office BP readings ii. Exclude white-coat HTN iii. Ensure adherence c. Identify and reverse contributing factors i. Lifestyle factors (a) Obesity (b) High-salt, low-fiber diet (c) Physical inactivity (d) Excessive alcohol use ii. Interfering medications (a) NSAIDs (b) Sympathomimetics (c) Stimulants (d) Oral contraceptives d. Screen and treat for secondary causes of HTN (described earlier) e. Assess for target organ damage f. Pharmacological treatment i. Maximize diuretic therapy (a) Use thiazide or thiazide-like diuretics if eGFR > 25-30 mL/min/m2 (1) Chlorthalidone and indapamide have the most evidence for reducing cardiovascular outcomes (2) Chlorthalidone is more effective at inducing predictable natriuresis in patients with an eGFR 30-45 mL/min/m 2 (b) Use loop diuretics if eGFR < 30 mL/min/m2 ii. Add ARA (spironolactone or eplerenone) iii. Alter dosing times to include a nocturnal dose or divide doses of drugs with half-lives <12-15 hours iv. Add other agents from different drug classes v. Addition of hydralazine or minoxidil requires concomitant use of a ß-blocker and diuretic g. Follow-up i. Ensure attainment of target BP after six months of therapy ii. If patient not at goal, refer to appropriate specialists IV. DYSLIPIDEMIA A. T  he AHA/ACC released updated Cholesterol Guidelines in 2018 in conjunction with 10 other organizations. Major changes in new guidelines: 1. Emphasis on personalized risk assessment and shared decision making using tools listed in (D) below 2. Re-introduction of LDL-C and non-HDL-C goals 3. Recommendations for statin and nonstatin therapies B. Goals of Therapy 1. Reduce CV morbidity and mortality 2. Achieve LDL-C goals, when appropriate ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-105 Chronic Care in Cardiology C. Nonpharmacologic recommendations 1. Lifestyle modification is cornerstone of initial intervention 2. Heart-healthy diet a. Recommend healthy diets such as the Dietary Approaches to Stop Hypertension (DASH) diet or the Mediterranean Diet b. Emphasize consumption of fruits, vegetables, whole grains, low-fat dairy products, skinless poultry and fish, nuts and legumes, and nontropical vegetable oils c. Limit sweets, sugar-sweetened beverages, and red meats d. Lower intake of saturated fats and replace with unsaturated fats (especially polyunsaturated fats) 3. Regular exercise 4. Engage in moderate-to-vigorous intensity aerobic physical activity 3-4 times per week for an average of 40 minutes per session 5. Smoking cessation D. Pharmacologic recommendations 1. Therapy recommendations are divided into patient management groups: a. Secondary ASCVD prevention b. Severe hypercholesterolemia (LDL-C ≥190 mg/dL) c. Diabetes mellitus (DM) d. Primary prevention 2. Pharmacologic management of dyslipidemia is detailed in Figure 7, and general principles are described below: a. First, initiate statin therapy if indicated. Optimize statin therapy (high intensity or maximally tolerated dose) before adding nonstatin therapy b. Second, consider nonstatin therapy if additional LDL lowering is warranted. c. According to the 2018 ACC/AHA management of blood cholesterol guidelines, ezetimibe should generally be the first nonstatin therapy considered, followed by the addition of a proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) monoclonal antibody (mAb) in selected patient groups (Figure 7). d. Of note, the 2022 ACC expert consensus pathway provides alternative recommendations. i. Either ezetimibe or PCSK9 mAbs may be considered as first-line adjunctive therapy to maximally tolerated statin therapy for patients with known ASCVD or baseline LDL of 190 mg/dL or greater. PCSK9 mAbs may be preferred in patients who require greater than 25% additional LDL lowering. ii. If further LDL lowering is warranted, the addition of the other nonstatin agent (ezetimibe or PCSK9 mAb) may be considered second. iii. If a third nonstatin therapy is warranted, the addition of bempedoic acid or the replacement of a PCSK9 mAb with inclisiran may be considered. 3. Special populations a. Patients age >75 years i. Reasonable to initiate a moderate-intensity statin or continue a moderate- or high-intensity statin if benefits outweigh risks ii. Reasonable to discontinue statin therapy if patients have functional decline, multimorbidity, frailty, or reduced life expectancy limits potential benefits b. Hypertriglyceridemia i. Primary goal is to prevent pancreatitis ii. Evaluate for secondary causes (Table 15) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-106