MANAGEMENT OF ATRIAL FIBRILLATION

Mary N. Healy, MS, ARNP-BC

Heart & Vascular Center of Sarasota

OBJECTIVES

1. Define the difference between paroxysmal and persistent Atrial Fibrillation

2. State the CVA risk per year of a 68 yr old female with hypertension that presents with new onset paroxysmal atrial fibrillation

3. Discuss two reasons to pursue rhythm control over rate control

4. Name 2 patient conditions in which warfarin is the only safe consideration for thromboembolic events in AF

5. Idenitify one drug that can be used for pharmacologic cardioversion to restore normal sinus rhythm

Pearls of AF Management• Address underlying triggers

• Hyperthyroidism, hypertension, obesity, alcohol, OSA, U/LRI

• Everyone needs rate control (to improve symptoms & prevent tachycardia related cardiomyopathy)• <80 at rest and <110 most simple activity-assess with Holter

monitor• Use beta blocker if pt has CHF or CAD• Use non-dihydropyridine CCB in those with COPD or asthma• If more rate control needed, add digoxin

• Rate vs Rhythm control• AFFIRM and RACE trials showed that mortality rates were slightly

better with rate control. However the exceptions are: <65, those with CHF, those with persistent symptoms despite rate control

Pearls of AF Management• Drugs or Ablation for Rhythm Control

• Opportunity for shared decision-making. Ablation more successful, but is associated with more risk. If drugs not successful, follow with ablation.

• Amiodarone has benefit of both rate and rhythm control, but has serious potential side effects

• When to Anticoagulate and What Drug to Use • Make life easy, download an app to your phone to figure

CHA2DS2VASc & HAS-BLED score https://itunes.apple.com/us/app/cardio-calculator/id955390696?mt=8

• CHA2DS2VASc of 2 or more and HAS-BLED score of < or = 3 warrant anticoagulation with warfarin or a novel oral anticoagulant

APP for Thromboembolic Risk

Pearls of AF Management• Use warfarin in those with valve replacement, mitral stenosis, end-

stage kidney disease or on dialysis• If you use a novel anti-coagulant with chronic kidney disease, the

dose needs to be reduced• In the elderly with the novel agents, periodically re-evaluate renal

function do determine if dosage changes should be made• Dual antiplatelet therapy (aspirin + clopidogrel) is no longer

recommended due to risk of bleeding

INTRODUCTION TO AF

Incidence/Scope of the Problem

• Mechanisms causing AF are multi-factoral, making it a complex and many times difficult for practitioners to manage.

• Symptoms range from non-existent to severe. • Frequent hospitalizations, thromboembolic events, hemodynamic disruptions result in significant morbidity and mortality.

Scope of Problem Stroke/CHF/Dementia Risk

• 5 fold increase risk of stroke, and stroke risk increases with age

• AF related stroke is likely to be more severe than non-AF stroke

• 3 fold risk of CHF• 2 fold increased risk of dementia as well as death

Scope of ProblemCosts

• Hospitalizations with AF as the primary diagnosis accounts for >467K admits in the US.

• >100K deaths/year• Pts. with AF are twice as likely to be hospitalized & 3 times more likely to have multiple hospitalizations

• Treating pts. with AF adds ~$26 billion to the US healthcare bill annually.

• Affects 6.1 million American adults and is expected to double in the next 25 years.

Definition of Atrial Fibrillation• AF is a supraventricular tachyarrhythmia with

uncoordinated and ineffective atrial contraction• Characterized by;

• Irregular R-R intervals• Absence of P waves• Irregular atrial activity (fibrillation waves)

Mechanisms of Atrial Fibrillation

Patient Assessment

Triggers of AF

• Hyperthyroid• ETOH use• Recent Pulm. Infection• OSA• Smoking• Immediate post-surgery• Inordinate Stress• Electrolyte Imbalance

Risk Factors

• Increasing Age• European ancestry• FH/Genetics• LVH/LAE/Mitral Valve Dis.• CHF• DM• MI• HTN• Obesity

Patient Assessment

Chief Complaint

• May be asymptomatic especially if >65 yr.

• Fatigue• Palpitations• SOB• Dizziness• Syncope• Frequent urination

Physical Findings

• Irregular pulse• Irregular JVP• Variation of intensity of S1• May also find:

• CHF symptoms• Valvular murmur of MR or

MS

Suggested Treatment Algorithm

REDUCING THROMBOTIC RISK

Priority #1 in AF/Reduce Embolic Risk

• Therapy based on shared decision making

• Base on risk of TE risk regardless of pattern (paroxysmal, permanent, etc)

• In non-valvular AF, CHA2DS2-VASc is recommended assessment of CVA risk

• For pts with artificial heart valves, warfarin is recommended.

• Balancing the Risks and Benefits• Non-valvular AF

increases CVA risk x5.• AF in presence of mitral

stenosis, increases CVA risk x 20 over those in NSR

90% of strokes from AF are caused by a clot in the left atrial appendage

Antithrombotic Options• Prevent strokes and systemic emboli in part by reducing

the formation of platelet rich or thrombotic clots in the LA or LA appendage

• Clinical Trials have looked at Warfarin vs aspirin; aspirin with warfarin or clopidogrel (Plavix®) and aspirin; warfarin vs. aspirin and clopidogrel; warfarin vs. direct thrombin inhibitors (dabigatran-Pradaxa®); warfarin vs. Xa inhibitors (Apixaban-Eliquis® & rivaroxaban-Xarelto®)

Coag Cascade and Antithrombotics

Warfarin• Vitamin K antagonist (VKA) in use since the 1950’s.• Works on multiple sites of the coagulation cascade-

Factor IX, VII, X, II

Pros• Inexpensive, available as generic• When INR therapeutic, significant risk reduction in stroke risk

Cons• Narrow therapeutic window • Increased risk of serious bleeding, including brain• Interaction with other drugs• Effects of alterations in diet• Freq. blood tests- therapeutic range achieved only ~55% of time

Dabigatran• Direct Thrombin Inhibitor• 150mg BID superior to warfarin in stroke, systemic

embolism. Hemorrhagic strokes, less, but major bleeds-non inferior to warfarin. Average CHADS score 2.1

• Also available 75mg BID for CrCl 15-30 mL/min-this dose never studied.

Pros• No blood testing• No drug or dietary interaction

Cons• BID dosing• High price

Rivaroxaban• Direct factor Xa inhibitor (excreted by kidneys)• Studied older pts and mean CHADS score was 3.47• Non-inferior to warfarin in stroke risk and major bleeding,

but did have less fatal bleeding and less brain bleeds. • Dose is 20mg daily with evening meal for CrCl>50mL/min

or 15mg for CrCl 30-49mL/min

Pros• No blood testing• Once daily dosing (though is with evening meal)• Minimal drug and no dietary interactions

Cons• Expensive

Apixaban• Direct factor Xa inhibitor (eliminated hepatically and highly

protein bound)• Significantly better than warfarin in reducing strokes (both

ischemic and hemorrhagic), systemic emboli and major bleed events. Fewer deaths than warfarin

• Average CHADS 2.1, mean age 70• Dosing-5mg bid unless meet two of the following: age > or

= to 80, weight < or = to 60Kg, serum creatinine >=1.5mg/dL, then 2.5mg bid

Pros and Cons• Similar to the other novel anticoagulants

General considerations in choosing anticoagulants

• If stable on warfarin and pt is happy with blood testing, etc, no need to change

• Medicare pts are covered if they wish, to do home monitoring checks-may increase the time in therapeutic range

• Reversing warfarin:

Aquamephyton (Vitamin K) usually po, is available IV, takes several hours to reverse

FFP infusion, time to reverse

Anticoag Considerations, cont’d

• If warfarin chosen as anticoagulant, it will take AT LEAST 5 days, and probably longer to achieve therapeutic INR, strongly consider using subq heparin, or enoxaparin to bridge until therapeutic

• Pt education required to counsel on testing, drug & food interactions

• Novel anticoagulants are approved in AF for “non-valvular” AF. Also approved for other indications, DVT, PE, but NOT FOR METAL VALVES

• Rapid onset and offset of action so bridging is usually not needed.

• Strict compliance with new agents is critical

Role of Antiplatelets• Limited data on the benefit of aspirin

• In primary prevention of stroke in AF, may reduce risk by 0.8%/yr (# needed to treat-125)

• For secondary prevention in those with TIA or strokes aspirin associated with risk reduction of 2.5%/year (# needed to treat-40)

• These data based on meta analysis. In the study that showed the most benefit, 325mg dose was used

• Aspirin ineffective in preventing strokes in those >75 and did not prevent severe strokes

• Clopidogrel + aspirin• Better than aspirin alone, but benefits are tempered by a significant

increase in major bleeding events• Studies show clear benefit of warfarin over C+A and Eliquis over

C+A

HAS-BLED score for bleeding risk on oral anticoagulation in atrial fibrillation

Feature Score if present• HTN (Systolic ≥ 160mmHg) 1• Abnormal renal function 1• Abnormal liver function 1• Stroke in past 1• Bleeding 1• Elderly 1 • Labile INRs 1• Drugs

• NSAIDS, antiplatelets 1

• ETOH 1

NON-PHARMACOLOGIC STROKE PREVENTION

Left Atrial Appendage (LAA) Occlusion By:WATCHMAN Device (Boston Scientific)Amplatzer cardiac plug (St. Jude)

LAA Occlusion by using LARIAT (SentreHEART) device that ties off the LAA “epicardial snare”

Requires subxiphoid pericardial approach

Surgical excision of the LAA for pts undergoing cardiac surgery

Yields inconsistent results

Masoudi FA, Calkins H, Kavinsky C; 2015 ACC/HRS/SCAI Left atrial Appendage Occlusion Device Societal Overview, JACC 2015;Jun 29

RATE CONTROL Resting rate < or = to 80, or average awake rate <100

Exercise rate should not exceed >100% of maximum predicted exercise rate

Rationale for Rate Control• This is an important strategy as it

• Impacts QOL• Reduces morbidity• Decreases potential for developing tachycardia induced

cardiomyopathy

• When selecting which agent(s) to use, must consider symptoms, hemodynamic status, presence of HF• Beta blockers, non-dihydropyridine CCB’s, digoxin, amiodarone,

sotalol are the main considerations

• When rapid control of ventricular rate during AF required, IV meds or electrical CV may be used. • May increase TE risk in those inadequately anticoagulated

AV Node Ablation as Rate Control Strategy

• Permanent Pacemaker implantation with subsequent AV node ablation effectively controls and regularizes ventricular heart rate and in select patients, improves symptoms

• Those most likely to benefit are those with symptomatic AF with RVR that is either non responsive to medications or the pt is intolerant to the meds

• Usually reserved for the elderly, as it makes one pacemaker dependent• Rate control meds no longer needed, but still require

anticoagulation

RHYTHM CONTROL

Rationale for Rhythm Control • This is a chance for shared decision making with the pt. • Always treat precipitating or reversible causes first• All rhythm control options should be considered only

under optimal TE prevention strategies.• If symptoms not controlled with rate regulation, or pt less

than 65 yrs old, it is reasonable to pursue restoration of NSR

• Choices include Pharmacologic, Ablation, Electrical Cardioversion alone or in combination

• Drugs that can convert: Amiodarone (IV/PO), Dofetilide (PO), Flecainide (PO), Propafenone (PO), Ibutilide (IV)

Drug Selection for Rhythm Control

AF Ablation• Invasive procedure to isolate the atrial impulses causing

AF and ablating those electrical pathways. Most common way is using radio frequency ablation, but cryo-ablation is now also being used.

• Associated with higher risk than antiarrhythmic drugs, but is generally more effective over the long term.

• Usually recommended for pts with symptomatic paroxysmal or persistent AF who are refractory or intolerant to at least 1 antiarrhythmic drug

Electrical Cardioversion• Recommended for symptomatic AF with RVR that does

not respond promptly to pharmacologic therapies and contributes to ongoing ischemia, hypotension or CHF

• Ideally, should be anticoagulated for 3 weeks prior, placed on an antiarrhythmic med, with a TEE to rule out intra-atrial clot, cardioversion then performed immediately following TEE. If clot is seen, CV is not performed.

• If AF is clearly less than 48 hours in duration, CV can be performed without TEE. Pt. should be anticoagulated ASAP.

• TE is most likely to occur within 72 hours after CV, can be as long as 10 days.

References• Cairns JA, Connolly S, McMurtry S, Stephenson M, Talajic M; CCS

Atrial Fibrillation Guidelines Committee. Canadian cardiovascular society atrial fibrillation guidelines 2010: prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter. Can J Cardiol. 2011 Jan-Feb;27(1):74-90.

• Prystowsky EN, Padanilam BJ, Fogel, RI. Treatment of Atrial Fibrillation. JAMA. 2015;314(3):278-288.

• Moss JD, Cifu, AS. Management of Anticoagulation in Patients with Atrial Fibrillation. JAMA. 2015;314(3):291-292.

• Chugh, A, Masoudi FA, Calkins H, Davisnsky, C. 2015 ACC/HRS/SCAI Left Atrial Appendage Occlusion Device Societal Overview. JACC. 2015: June 29.

• January, CT, Wann, LS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. JACC. Vol 64, No 21. e1-79.