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A Review of Atrial Fibrillation and Current Therapeutic Strategies: Part 2

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December 1, 2019

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Table of Contents

A Review of Atrial Fibrillation and Current Therapeutic Strategies: Part 2

Financial Disclosure: To reveal any potential bias in this publication, and in accordance with Accreditation Council for Continuing Medical Education guidelines, Dr. Wise (editor) reports he is involved with sales for CNS Vital Signs and Clean Sweep. Dr. Mwansa (author), Dr. Mazimba (author), Dr. Solomon (peer reviewer), Mr. Schneider (editor), Ms. Mark (executive editor), Ms. Coplin (editorial group manager), and Ms. Johnson (accreditations manager) report no financial relationships with companies related to the field of study covered by this CME activity.

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Table 1. Antiarrhythmic Drugs (AADs) Commonly Used for Rhythm Management of AF
Drug	Class	Contraindications and Potential Adverse Effects
Amiodarone*	IB, III	Contraindicated in severe sinus node dysfunction, second and third degree AV block, and cardiogenic shock Proarrhythmic with potential for torsades de pointes; caution with a prolonged QT, concomitant use of QT-prolonging medications (e.g., macrolides, TCAs, thiazides), and SA node and AV node dysfunction Reduce doses of digoxin and VKAs if administered concurrently with amiodarone (reduces hepatic and renal clearance) Increased risk of statin myopathy (inhibits hepatic P450, leading to increases in serum concentration of statins) Associated with thyroid, hepatic, and pulmonary toxicity
Dronedarone	IB	Contraindicated in patients with recently decompensated NYHA class II-III HF, NYHA class IV HF, and/or permanent AF (increased mortality),¹⁷ concomitant use of strong CYP3A4 inhibitors (e.g., azole antifungals, macrolides, etc.), bradycardia < 50 bpm, second and third AV block, SSS, QTc > 500 msec or PR interval > 280 msec, concomitant use of other QT-prolonging drugs given its potential for TdP, liver injury related to amiodarone, and severe hepatic impairment (Child-Pugh Class C)
Flecainide*	IC	Contraindicated in IHD (increased mortality observed post MI¹⁸ and HF with significant LV dysfunction, second and third degree AV block) Caution in liver disease, renal dysfunction with CrCl < 50 mg/mL; concurrent use with CYP2D6 inhibitors (e.g., SSRIs and TCAs) increases plasma concentration and elevates risk for adverse effects
Propafenone	IC	Contraindicated in significant IHD, HF with LV dysfunction (has negative inotropic and chronotropic effects), significant hypotension, bradycardia, SA node and/or AV node disease, severe bronchospastic disease (e.g., asthma), known Brugada syndrome (can unmask disease) and co-administration with ritonavir Proarrhythmic effects may include sudden cardiac death via ventricular fibrillation, Tdp, asystole, etc. Predominantly metabolized via the liver and caution is warranted in liver disease
Ibutilide*	III	Contraindicated with QTc > 440 msec, concurrent QT-prolonging drugs and/or congenital QTc syndrome due to potential for polymorphic ventricular tachycardia and TdP Caution in patients with bradycardia, congestive HF, severe LVH, recent MI, and electrolyte abnormalities (hypokalemia and hypomagnesemia)
Procainamide*	IA	Contraindicated in second and third degree AV block, TdP, and SLE Caution in IHD, cardiomyopathy, HF, blood dyscrasias (cytopenias), and liver, and renal dysfunction
d, I Sotalol	II, III	Contraindicated in sinus bradycardia < 50 bpm, SSS, second and third degree AV block, baseline QT interval > 450 msec, acquired and congenital long QT syndromes, significant LV dysfunction, cardiogenic shock, hypokalemia < 4 mEq, CrCl < 40 mL/min, asthma Caution with renal insufficiency and concomitant use of QT-prolonging drugs
*AADs also used for pharmacologic cardioversion AV = atrioventricular; TCAs = tricyclic antidepressants; SA = sinoatrial; VKAs = vitamin K antagonists; NYHA = New York Heart Association; HF = heart failure; SSS = sick sinus syndrome; QTc = corrected QT interval; TdP = torsades de pointes; msec = milliseconds; IHD = ischemic heart disease; MI = myocardial infarction; LV = left ventricular; CrCl = creatinine clearance; SSRIs = selective serotonin reuptake inhibitors; TdP = torsades de pointes; LVH = left ventricular hypertrophy; SLE = systemic lupus erythematosus; mEq = milliequivalents

Table 2. CHA₂DS₂-VASc Score for Stratification of Thromboembolism Risk in Nonvalvular AF
CHA₂DS₂-VASc risk factor⁷⁹	Score
Congestive heart failure Symptoms/signs of congestive HF or objective evidence of reduced LVEF	1
Hypertension (confirmed diagnosis or presence of antihypertensive drug therapy)	1
Age ≥ 75 years	2
Diabetes mellitus (confirmed diagnosis or active pharmacotherapy for the disease)	1
Prior stroke/TIA/Thromboembolism	2
Vascular disease (prior MI, PAD, or aortic plaque)	1
Age 65-74 years	1
Sex category (female)	1
CHA₂DS₂-VASc = Congestive HF, HTN, Age ≥ 75 (doubled), Diabetes, Stroke/TIA/Thromboembolism (doubled), Vascular disease (CAD, PAD, and aortic plaque), Age 65–74, and Sex (female); LVEF = left ventricular ejection fraction

Table 3. Current FDA-approved NOACs
	Dabigatran	Rivaroxaban	Apixaban	Edoxaban
Peak time (hours)	1-3	1-4	1-3	1-2
Protein binding	35%	92-95%	87%	55%
Half-life (hours)	12-17	5-13	9-14	10-14
Clearance	80% renal	66% hepatic; 33% renal	25% renal	50% renal
Drug interactions and dosage considerations	Renal dysfunction: CrCl > 30 mL/min: 150 mg bid CrCl 15-30 mL/min: 75 mg bid Consider dose adjustment with concomitant P-gp inducer (e.g. rifampin) and inhibitor (e.g. dronedarone & ketoconazole) use	Renal dysfunction: CrCl > 50 mL/min: 20 mg qd with evening meal CrCl 15-50 mL/min: 15 mg qd with evening meal Caution with moderate to severe hepatic impairment Avoid concomitant use with dual P-gp and strong CYP3A4 inhibitors (e.g. azole antifungals) and dual P-gp and strong CYP3A4 inducers (e.g. carbamazepine)	Usually 5 mg bid Presence of ≥ 2 of the following: age 80 years, body weight 60 kg, or serum creatinine 1.5 mg/dL, the recommended dose is 2.5 mg bid Strong dual inhibitors of CYP3A4 and P-gp increase serum levels of apixaban: give 2.5 mg bid if not possible to avoid concomitant use Strong inducers of CYP3A4 and P-gp reduce serum levels of apixaban; avoid use	60 mg qd if CrCl > 50 to ≤ 95 mL/min 30 mg qd if CrCl 15-50mL/min Contraindicated if CrCl > 95 mL/min
Antidote	Idarucizumab	Andexanet alfa	Andexanet alfa
FDA = U.S. Food and Drug Administration; CrCl = creatinine clearance; qd = once daily; bid = twice daily

Table 1. Antiarrhythmic Drugs (AADs) Commonly Used for Rhythm Management of AF

Figure 1. Pharmacologic Conversion

Table 2. CHA₂DS₂-VASc Score for Stratification of Thromboembolism Risk in Nonvalvular AF

Table 3. Current FDA-approved NOACs

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A Review of Atrial Fibrillation and Current Therapeutic Strategies: Part 2

AUTHORS

PEER REVIEWER

EXECUTIVE SUMMARY

Long-Term Management of Atrial Fibrillation

Rate Control Strategy

Nonpharmacologic Rate Control

Rhythm Control Strategy

Table 1. Antiarrhythmic Drugs (AADs) Commonly Used for Rhythm Management of AF

Figure 1. Pharmacologic Conversion

Catheter Ablation for AF

Ablation of AF in HF Patients

AF Surgery

Prevention of Stroke and Systemic Thromboembolism in AF

Table 2. CHA2DS2-VASc Score for Stratification of Thromboembolism Risk in Nonvalvular AF

Thromboembolism Prevention in AF

Thromboembolism Prevention in Valvular AF

Table 3. Current FDA-approved NOACs

Nonpharmacological Thromboembolism Prevention in AF

Postoperative AF Management

Summary

REFERENCES

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Table 2. CHA₂DS₂-VASc Score for Stratification of Thromboembolism Risk in Nonvalvular AF