ATRIAL FIBRILLATION and FLUTTER - Amazon S3...Atrial Fibrillation with Slow VR Just because the ventricular rate is slow, doesn’t mean that it is NOT atrial fibrillation May be due

ATRIAL FIBRILLATION: FOCUSED UPDATE FOR THE PCP

Kevin Mikielski, DO, FACC

LOMA 2016

OBJECTIVES

Recognize that defining atrial mechanism is extremely important on EKG

Understand how CHADS-VASC score predicts thromboembolism risk

Recognize that ASA is inferior to anticoagulation in patients with high risk

CHADS-VASC score

Recognize that NOACs should NOT be used in patients with mechanical

valves

Understand risks versus benefits when comparing Warfarin vs NOACs

Know how long to hold anticoagulants prior to elective surgery

ATRIAL FIBRILLATION

Definition and Background

Supraventricular tachyarrhythmia with uncoordinated atrial activation and

consequently ineffective atrial contraction

EKG characteristics:

1) irregular R-R intervals

2) absence of distinct repeating P waves

3) irregular atrial activity

Atrial Fibrillation with Slow VR

Just because the ventricular rate is slow, doesn’t mean that it is NOT atrial fibrillation

May be due to:

AV nodal blocking agents

Intrinsic conduction system disease/SSS

Complete heart block-VR will be regular

Conduction system disease due to conditions such as sarcoidosis, amyloidosis, Lyme, etc.

VERY IMPORTANT!!!

Must identify and report the underlying

atrial mechanism/rhythm

Failure to do so may result patient not

receiving anticoagulation and will be at

higher risk for stroke/thromboembolism

Reporting only “Ventricular Pacing” is not

sufficient

EPIDEMIOLOGY

Most common cardiac

arrhythmia

Prevalence: 1.2 million;

expected to increase to 2.6

million by 2030

Significantly increases with

age

By age 85, approximately

12.5% of people will have

been diagnosed with atrial

fibrillation

MAJOR RISK FACTORS FOR

DEVELOPING A FIB

Hypertension

Most prevalent RF-accounts for over 16% of cases

Markedly increases risk further if LVH present on EKG

Age

DM

CHF

Both HFREF and HFPEF

Male gender

Valvular disease

Especially MR and MS

Sleep apnea

Obesity

Tobacco use

All of above factors increase

INFLAMMATION and activation of the

Renin-Angiotension-Aldosterone

system-All cause increased cardiac

irritability.

Mechanisms of Atrial Fibrillation-

Multiple Wavelets vs Foal Trigger

Atrial rate of 400-600 bpm

Ventricular rate of 140-220 bpm

Less than atrial rate because of decrimental/concealed conduction

Protective to prevent ventricular fibrillation

Patients would die if VR was 400-600 bpm

Would result in ventricular fibrillation

Usually conduction occurs fat ratio of 4-2:1

VR may be slower if AV nodal conduction system disease present

CLASSIFICATION OF ATRIAL

FIBRILLATION

SYMPTOMS

Palpitations; rapid heart action

Dyspnea

Chest pain

Especially if rapid ventricular rate results in subendocardial ischemia in setting of

CHF/CAD/aortic stenosis

Fatigue

Edema

ASYMPTOMATIC!!!

Many patients will NOT have palpitations and may only have vague symptoms

TREATMENT GOALS

Modify risk factors

Both to prevent development and reduce recurrences/paroxysms

Control ventricular rate

Restore sinus rhythm if indicated

Prevent stroke/thromboembolism

Most of the Risk Factors are Modifiable!

LEGACY TRIAL: All patients had Paroxysmal or

Persistent A fib and a BMI > or = to 27

Significant reductions in ablation/antiarrhythmic drug therapy and total AF

burden in patients that lost weight and/or improved MET level

VENTRICULAR RATE CONTROL

Old mantra was to keep VR less than 100 bpm

All med classes below can be used acutely and chronically

Medication classes include:

Beta Blockers-Most effective

Calcium Channel Blockers-Nondihydropyradine Class

Dihydropyridines Amlodipine and Nifedipine have no significant effect on AV node

Digoxin

Less effective particularly with exertion but may need to use if BP low/borderline low or if systolic heart failure present (Verapamil and Diltiazem are negative inotropes)

Narrow therapeutic window-don’t rely on “therapeutic range” as shown in DIG TRIAL

Antiarrhythmic drugs such as Amiodarone

If all else fails, can refer to EP for AV node ablation with PPM

RACE II TRIAL

Compared strict (<80 bpm at rest) vs lenient (<110 bpm at rest) VR control in patients with PERMANENT a fib.

Primary outcome was composite of death from cardiovascular causes, hospitalization for CHF, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events.

No significant difference in adverse events and symptoms between groups

CONCLUSION: In patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve.

If patient is doing well clinically, do not be “obsessed” with strict VR

control. Exceptions include symptomatic patients and if HFREF is present-

controlling VR may prevent further deterioration of LV systolic function.

RHYTHM CONTROL

OPTIONS

Electrical cardioversion

Need to document therapeutic INR/anticoagulation for 3-4 weeks before procedure and then at least 3-4 weeks afterward

If INR has been subtherapeutic or if patient not on AC for 3-4 weeks, will need TEE to document absence of left atrial appendage thrombus

My practice: Would not electively cardiovert while only on antiplatelet therapy

Antiarrhythmic drugs

Most commonly used are:

Amiodarone: Most effective but multiple organ system-related side effects

Dronedarone (Multaq): Cannot use if recent CHF exacerbation or permanent a fib

Sotalol: Not indicated for conversion but used to maintain sinus rhythm

Dofetilide (Tikosyn): Usually only prescribed by EP

Very important that electrolytes atnd QT interval be closely monitored, especially with Sotalol and Dofetilide-risk of Torsades de Pointes

Case Study

77 yo white female with pulmonary fibrosis/COPD, diastolic CHF, and

paroxysmal atrial fibrillation

Placed on Tikosyn for symptomatic a fib

Doing well for 6 months but developed URI and placed on antibiotics;

decreased PO intake and then diarrhea

2 syncopal episodes

Called office and told to go to ER (lives 120 miles away)

Labs: K-3.0. and Mag-1.3

In ER

QT-740 msec!!!

Then . . . Near Syncope but spontaneously

converted to sinus rhythm

Antiarrhythmic Drugs: Take Home

Points

They have a place in the treatment armamentarium

But, need to be extremely diligent with regards to electrolytes, bradycardia

(may prolong QT), drug interactions

Ask yourself . . . Does my patient really need to be on this medication?

Refer or defer question to cardiology is unsure.

AFFIRM TRIAL

RATE VS RHYTHM CONTROL

No survival benefit by maintaining sinus rhythm

More hospitalizations with antiarrhythmic drug therapy

Postulated to be secondary to medication-related side effects

TAKE HOME POINTS: Reserve rhythm control for symptomatic patients or those with compelling indications to maintain sinus rhythm. Often times side effects from antiarrhythmic drugs are worsen that symptoms from a fib

ANATOMY OF PULMONARY VEINS

VERY COMPLEX!!!

-Atrial myocardium encircles the ostia of pulmonary veins

-Foci for initiation of atrial fibrillation

-Provides targets for pulmonary vein isolation/ablation

PULMONARY VEIN ISOLATION-RADIOFREQUENCY ABLATION

TREATMENT OPTION FOR ATRIAL FIB

Completely encircle pulmonary veins with intracardiac catheter

“Isolation” of pulmonary veins

Best utilized in patients who are refractory to medical therapy

Should not be considered a “cure”

Do not refer for the sole purpose of not using anticoagulation

Not indicated when patient says “Do the procedure so I don’t have to take Coumadin.”

Patient should remain on anticoagulation after procedure

Rely on cardiologist to decide about continuing anticoagulation

RADIOFREQUENCY VS

ANTIARRHYTHMIC DRUG THERAPY

Efficacy of therapies:

RFA-70%

Antiarrhythmics-19%

However, guidelines still

recommend failure of one

antiarrhythmic drug prior to

referral for ablation

PULMONARY VEIN ISOLATION-

CRYOABLATION

Uses “deep freeze”

catheter to ablate

within ostium of

pulmonary veins

Similar efficacy to

radiofrequency

ablation

STOP AF TRIAL

CRYOABLATION VS AAD THERAPY

Patients needed to have failed one AAD drug prior to randomization

Cryoablation superior to antiarrhythmic drug therapy for preventing atrial fibrillation occurrence

COMPLICATIONS OF ABLATION

Pulmonary vein stenosis

1%

Present with dyspnea, hemoptysis, and chest pain 1-6 months after procedure

Left atrial-esophageal fistula

0.1%-improved with better temperature-monitoring probes

Alerts EP to “heating up” of esophagus during RFA procedure

Odynophagia, fever/systemically ill, stroke

Occurs within 1 month of procedure

Very high mortality

Phrenic nerve injury

More common with cryoablation

Pericardial tamponade

THE MOST FEARED COMPLICATION OF

ATRIAL FIBRILLATION!!!!!

PREVENTION OF

STOKE/THROMBOEMBOLISM

Main goal/target in treatment of atrial fibrillation

Need to evaluate stroke vs bleeding risk on individual basis

CHADS2-VASC risk stratification score has become “gold standard” in assessing stroke risk

Remember: Antiplatelet and anticoagulants are not the same

Antiplatelet agents such as Aspirin and Clopidogrel reduce platelet aggregation and are not “blood thinners”

Anticoagulants inhibit action/synthesis of clotting factors and are classified as “blood thinners”

Stroke/thromboembolism in atrial fibrillation is due to thrombus formation not platelet aggregates

Different from ACS

ANTIPLATELET THERAPY FOR STROKE

AND SYSTEMIC EMBOLISM REDUCTION

Antiplatelet agents do not “thin

the blood”

Ultimately reduce platelet

aggregation

INR and PTT should be normal

when on these agents unless

another process/medication is

present

ASPIRIN VS PLACEBO FOR STROKE

PREVENTION

Only SPAF-1 showed benefit; all

other trials neutral

Aspirin alone of marginal benefit for

reducing stroke based on Meta

Analysis-results driven by SPAF-1

Not effective for those >75 and

much less effective for secondary

prevention; does not protect from

severe stroke

Clopidogrel and Aspirin vs Aspirin Alone

Active A Trial

ACTIVE A Results Significant reduction in primary

composite endpoint (stroke,

myocardial infarction, non–central

nervous system systemic embolism, or

death from vascular causes) with

Clopidogrel and Aspirin vs Aspirin

alone

Significant reduction in stroke with

Clopidogrel and Aspirin vs Aspirin

alone

Higher bleeding risk with combination

therapy

CONCLUSION: Benefit of combination

therapy offset by significantly higher

bleeding risk; therefore, not

recommended in AHA/ACC

guidelines

ANTICOAGULATION FOR STROKE AND

SYSTEMIC EMBOLISM REDUCTION

Tested against placebo, ASA and other antithrombotic agents

WARARIN/VITAMIN K ANTAGONISTS

Inhibit production of clotting

factors II, VII, IX, and X

Levels of protein C and S also

decline

Ultimately reduce thrombin levels

Use PT or INR (more common) to

monitor therapeutic levels

Usually target INR of 2.0-3.0

WARFARIN VS PLACEBO FOR STROKE

PREVENTION

Warfarin superior to Placebo for

stroke reduction

Warfarin associated with

significantly higher bleeding risk

WARFARIN VS ASPIRIN FOR STROKE

PREVENTION

-Warfarin superior to Aspirin for

stroke reduction

-However, Warfarin associated with

significantly higher risk of bleeding

WARFARIN VS COMBINATION OF

CLOPIDOGREL AND ASPIRIN FOR STROKE

PREVENTION-ACTIVE W TRIAL

Warfarin superior to combination

of Clopidorel and Aspirin for

reducing primary composite

endpoint of stroke, systemic

embolism, MI and vascular death

Warfarin superior to combination

of Clopidogrel and Aspirin for

stroke reduction

ACTIVE W: MAJOR BLEEDING

No significant difference in major bleeding between Warfarin

and combination of Aspirin and Clopidogrel

Therapeutic Range for Warfarin

INR Values at Stroke or ICH

Od

ds

Ra

tio

0 5.0 6.0 8.0

INR 1.0 2.0 3.0 4.0 7.0

5.0

15.0

10.0

Stroke

1.0

Fuster et al. J Am Coll Cardiol. 2001;38:1231-1266.

Intracranial

Hemorrhage

Need to be in “Sweet Spot” to reduce stroke while not significantly increasing bleeding

Warfarin excellent when INR therapeutic but

not so good when INR sub- or

supratherapeutic

So, here come the New Kids on the

Block . . . The NOACs.

DABIGATRAN (PRADAXA)

Approved by FDA in 2010

Direct thrombin inhibitor

Half-life of 12-14 hours

BID dosing

No need to monitor INR

No common significant drug interactions

Patients can eat veggies

RELY TRIAL- DABIGATRAN VS WARFARIN

DESIGN

Randomized trial designed to compare two fixed doses of dabigatran (150 mg BID and 110 mg BID), each administered in a blinded manner, with open-label use of warfarin in patients who had atrial fibrillation and were at increased risk for stroke.

Patients were eligible if they had atrial fibrillation documented on electrocardiography performed at screening or within 6 months beforehand and at least one of the following: previous stroke or TIA, LVEF less than 40%, New York Heart Association class II or higher heart-failure symptoms within 6 months before screening, and an age of at least 75 years or an age of 65 to 74 years plus diabetes mellitus, hypertension, or coronary artery disease.

Key exclusion criteria included: presence of a severe heart-valve disorder (i.e., prosthetic valve or hemodynamically relevant valve disease), stroke within 14 days or severe stroke within 6 months before screening, a condition that increased the risk of hemorrhage, a creatinine clearance less than 30 ml per minute, and active liver disease.

RELY TRIAL

OUTCOMES-EFFICACY

Stroke or systemic embolism occurred in 182 patients receiving 110 mg of dabigatran (1.53% per year), 134 patients receiving 150 mg of dabigatran (1.11% per year), and 199 patients receiving warfarin (1.69% per year).

The 150-mg dose of dabigatran was SUPERIOR to warfarin.

The 110-mg dose was noninferior to warfarin.

CONCLUSION: 150 mg dose better than Warfarin in reducing stroke or systemic embolism.

RELY TRIAL

OUTCOMES-SAFETY

The rate of major bleeding was 3.36% per year in the warfarin group, as

compared with 2.71% per year in the group that received 110 mg of

dabigatran and 3.11% per year in the group that received 150 mg of

dabigatran.

Rates of life-threatening bleeding, intracranial bleeding, and major or minor

bleeding were higher with warfarin than with either the 110-mg dose and

150-mg of dabigatran.

There was a significantly higher rate of major gastrointestinal bleeding with

dabigatran at the 150-mg dose than with warfarin.

CONCLUSION: 150 mg dose safer than Warfarin with regards to bleeding,

and in particular, life-threatening and intracranial bleeding; trade-off is

higher GI bleed rate with Dabigatran.

DABIGATRAN

WHAT TO TELL PATIENTS

Don’t know what to say if the patient qualifies for 75 mg per day because this dose was not tested; 110 mg dose not available

Dabigatran better than Warfarin at preventing stroke and systemic embolism

Dabigatran safer than Warfarin with regards to bleeding with the exception of GI bleeding (this rarely kills people)

Can always give blood but cannot give back the brain!

Remember to check the CrCl:

Use 150 mg BID if CrCl more than 30 ml/min

Use 75 mg BID if CrCl between 15-30 ml/min

Don’t use if CrCl less than 15 ml/min

RIVAROXABAN (XARELTO)


Factor Xa inhibitor

Half-life of 6-12 hours; longer in elderly

But Factor Xa levels do not return to normal for 24 hours so drug can be used

qday

QDAY dosing




ROCKET AF- RIVAROXABAN VS WARFARIN

DESIGN

Randomized trial designed to compare fixed-dose rivaroxaban (20 mg daily or 15 mg daily in patients with a CrCl of 30 to 49 ml per minute) with adjusted-dose warfarin (target international normalized ratio [INR], 2.0 to 3.0) in patients with atrial fibrillation and at moderate-to-high risk for stroke.

Elevated risk was indicated by a history of stroke, transient ischemic attack, or systemic embolism or at least two of the following risk factors: CHF or LVEF of 35% or less, hypertension, an age of 75 years or more, or the presence of diabetes mellitus (i.e., a CHADS2 score of 2 or more, on a scale ranging from 1 to 6, with higher scores indicating a greater risk of stroke).

Key exclusion criteria included: hemodynamically significant mitral valve stenosis and prosthetic heart valve (annuloplasty with or without prosthetic ring, commissurotomy and/or valvuloplasty were permitted), a creatinine clearance less than 30 ml/min, and active liver disease.

ROCKET AF TRIAL

OUTCOMES-EFFICACY

Stroke or systemic embolism

occurred in 188 patients in the

rivaroxaban group (1.7% per year)

and in 241 patients in the warfarin

group (2.2% per year).

Rivaroxaban is NONINFERIOR but

not SUPERIOR to Warfarin

CONCLUSION: Rivaroxaban is

equivalent to Warfarin in reducing

stroke and systemic embolism.

ROCKET AF

OUTCOMES-SAFETY

Major and clinically relevant nonmajor bleeding occurred in 1475 patients

in the rivaroxaban group and in 1449 patients in the warfarin group (14.9%

and 14.5% per year, respectively). Events occurred at similar incidence.

Rates of intracranial hemorrhage were significantly lower in the rivaroxaban

group than in the warfarin group.

Major bleeding from a gastrointestinal site was more common in the

rivaroxaban group, with 224 bleeding events (3.2%), as compared with 154

events in the warfarin group (2.2%).

CONCLUSION: Rivaroxaban is similar to Warfarin with regards to total major

and nonmajor bleeding events. However, Rivaroxaban resulted in less

intracranial bleeding but with a higher GI bleeding incidence.

RIVAROXABAN

OH NO!

Legal Ramifications!

Document that you discussed bleeding risks with patient

I tell my patients that the drug’s most common side effect is bleeding-DUH!

But, the bleeding incidence is not higher compared to the GOLD

STANDARD, which is Warfarin

Case Study: My partner’s patient with atrial fib stopped Xarelto after seeing

TV ads and had a major stroke with hemiparesis

Did not call to discuss issue/concerns

Who should be responsible???

You should not be held accountable if you document as above, adjust

dose based on CrCl, and not use drug in off-label indication.

XARELTO


Xarelto equivalent to Warfarin at preventing stroke and systemic embolism

Xarelto equivalent to Warfarin with regards to bleeding events; less ICH but

higher GI bleeding incidence

Remember to check the CrCl:

Use 20 mg qday if CrCl more than 50 ml/min

Use 15 mg qday if CrCl between 15-50 ml/min

Don’t use if CrCl less than 15 ml/min

APIXABAN (ELIQUIS)


Factor Xa inhibitor

Half-life 9-14 hours

BID dosing




AVERROES TRIAL- APIXOBAN VS ASPIRIN

DESIGN

Patients were eligible if they were 50 years of age or older and had atrial fibrillation documented in the 6 months before enrollment or by 12-lead electrocardiography on the day of screening.

Patients also had to have at least one of the following risk factors for stroke: prior stroke or transient ischemic attack, an age of 75 years or older, HTN (receiving treatment), diabetes, CHF (New York Heart Association class 2 or higher at the time of enrollment), an LVEF of 35% or less, or documented PAD. In addition, patients could not be receiving vitamin K antagonist therapy, either because it had already been demonstrated to be unsuitable for them or because it was expected to be unsuitable. The reasons that vitamin K antagonist therapy was unsuitable for the patient had to be documented on the study case-report forms.

Patients were deemed to be Warfarin-ineligible!?!?

Patients were randomly assigned to receive apixaban (5 mg twice daily or 2.5 mg BID if 2.5 mg twice daily if two of the following criteria were met: an age of 80 years or older, body weight of 60 kg or less, or serum creatinine level of > 1.5 mg/dl).

AVERROES TRIAL

OUTCOMES-EFFICACY

Stroke or systemic embolism occurred in 51 patients assigned to apixaban and 113 (3.7% per year) assigned to aspirin. Trial terminated early.

CONCLUSION: Apixaban is SUPERIOR to Aspirin in reducing stroke and systemic embolism.

Tells us what we already knew!!!-Systemic anticoagulation is superior to antiplatelet therapy in reducing stroke and systemic embolism.

AVERROES TRIAL

OUTCOMES-SAFETY

There were 44 major bleeding

events (1.4% per year) among

patients taking apixaban and 39

(1.2% per year) among those

taking aspirin.

No significant difference in

intracranial bleeding with

Apixaban compared to Aspirin.

CONCLUSION: Apixaban did not

increase bleeding (incuding ICH)

compared to Aspirin.

ARTISTOTLE TRIAL- APIXABAN VS WARFARIN

DESIGN

Randomized trial designed to compare fixed-dose Apixaban (5 mg BID or 2.5 mg BID in patients with two or more of the following: age >80, weight < 60 kg, and creatinine >1.5 mg/dl) with adjusted-dose warfarin (target international normalized ratio [INR], 2.0 to 3.0) in patients with atrial fibrillation and at least one additional risk factor for stroke.

Eligible patients had atrial fibrillation or flutter at enrollment or two or more episodes of atrial fibrillation or flutter, as documented by electrocardiography, at least 2 weeks apart in the 12 months before enrollment. In addition, at least one of the following risk factors for stroke was required: an age of at least 75 years; previous stroke, transient ischemic attack, or systemic embolism; symptomatic heart failure within the previous 3 months or LVEF < 40%; diabetes; or HTN requiring treatment.

Key exclusion criteria included: moderate or severe mitral stenosis, conditions other than atrial fibrillation that required anticoagulation (e.g., a prosthetic heart valve), and severe renal insufficiency (serum creatinine level of >2.5 mg per deciliter [221 μmol per liter] or calculated creatinine clearance of <25 ml per minute).

ARISTOTLE TRIAL

OUTCOMES-EFFICACY

Stroke or systemic embolism occurred in 212 patients in the apixaban group (1.27% per year) as compared with 265 patients in the warfarin group (1.60% per year).

Apixaban superior to Warfarin in reducing stroke/systemic embolism.

The rate of death from any cause was also significantly lower in the apixaban group than in the warfarin group

Largely attributable to reduction in ICH

CONCLUSION: Apixaban superior to Warfarin in reducing stroke and systemic embolism as well as death.

ARISTOTLE TRIAL

OUTCOMES-SAFETY

Major bleeding occurred in 327 patients in the apixaban group (2.13% per year), as compared with 462 patients in the warfarin group.

The rate of intracranial hemorrhage was 0.33% per year in the apixaban group and 0.80% per year in the warfarin group.

The rate of any bleeding was 18.1% per year in the apixaban group and 25.8% per year in the warfarin group.

GI bleeding rate was similar between groups.

CONCLUSION: Apixaban safer compared to Warfarin.

APIXABAN


Apixaban better than Warfarin and Aspirin at preventing stroke and systemic embolism

Apixaban prevents death better than Warfarin

Largely due to reduction in intracranial hemorrhage

Apixaban better than Warfarin with regards to bleeding

Apixaban does not increase bleeding more than Aspirin

Remember to reduce the dose from 5 mg BID to 2.5 mg BID if 2 or more of the following are present:

Age 80 or over

Weight 60 kg or less

Creatinine 1.5 mg/dl or more

“ May be able to use” in patients with end stage renal disease based on extrapolated data but ACC/AHA guidelines still favor Warfarin in this setting

EDOXABAN (SAVAYSA)


Factor Xa inhibitor

Half-life of 10-14 hours

QDAY dosing




ENGAGE AF-TIMI 48 TRIAL-

EDOXABAN VS WARFARIN

DESIGN

Randomized, double-blind, trial comparing two once-daily regimens of edoxaban

(60 mg and 30 mg) with warfarin in 21,105 patients with moderate-to-high-risk atrial

fibrillation.

Eligible patients were 21 years of age or older and had atrial fibrillation

documented by means of an EKG within the 12 months preceding randomization,

a score of 2 or higher on the CHADS2 risk assessment, and anticoagulation therapy

planned for the duration of the trial.

Key exclusion criteria were an estimated CrCl of less than 30 ml/min, moderate-to-

severe mitral stenosis and other indications for anticoagulation therapy (including

mechanical valves).

ENGAGE TRIAL

OUTCOMES-EFFICACY

Stroke or systemic embolic occurred in 232 patients in the warfarin group (representing a rate of 1.50% per year), as compared with 182 patients in the high-dose edoxaban group (rate of 1.18% per year) and 253 patients in the low-dose edoxaban group (rate of 1.61% per year).

Both doses of Edoxaban resulted in lower incidence of cardiovascular death compared to Warfarin.

CONCLUSION: Both doses of Edoxaban are equivalent to Warfarin in reducing stroke and systemic embolism. Both doses reduce cardiovascular death more than Warfarin.

ENGAGE TRIAL

OUTCOMES-SAFETY

The annualized rate of major bleeding events was 3.43% with warfarin, as compared with 2.75% with high-dose edoxaban and 1.61% with low-dose edoxaban

Both doses of Edoxaban were associated with lower intracranial hemorrhage compared to Warfarin

High-dose Edoxaban increased GI bleeding compared to Warfarin and low-dose Edoxaban resulted in lower GI bleeding compared to Warfarin

CONCLUSION: Both doses of Edoxaban are safer than Warfarin with regards to major bleeding and intracranial hemorrhage. High-dose Edoxaban had a higher GI bleeding rate while low-dose had a lower GI bleeding rate compared to Warfarin.

EDOXABAN


Both doses of Edoxaban are similar to Warfarin at reducing stroke and systemic embolism.

Both doses of Edoxaban are better than Warfarin at reducing cardiovascular death.

Both doses of Edoxaban are safer than Warfarin with regards to major bleeding and intracranial hemorrhage.

Low-dose Edoxaban is safer than Warfarin with regards to GI bleeding

Warfarin is safer than high-dose Edoxaban with regards to GI bleeding

Remember to adjust dose:

–60 mg daily for CrCl 51-95 mL/min

–30 mg daily for CrCl 15-50 mL/min

–Not recommended if CrCl<15 or >95 mL/min

Usually CrCl results as >60 mL/min on BMP results. May complicate use of drug because high-dose was less effective in patients with high CrCl (postulated to be secondary to higher drug clearance and subsequent lower concentration).

SUMMARY-NOACS vs WARFARIN

Dabigatran

110

Dagibatran

150

Rivaroxaban

15

Rivaroxaban

20

Apixaban

2.5

Apixaban

5

Edoxaban 30 Edoxaban 60

CHADS2 2.1 2.1 3.5 3.5 2.1 2.1 2.8 2.8

Stroke and

systemic

embolism

EQUAL BETTER EQUAL EQUAL BETTER BETTER EQUAL EQUAL

Major bleeding BETTER EQUAL EQUAL EQUAL BETTER BETTER BETTER EQUAL

Intracranial

hemorrhage BETTER BETTER BETTER BETTER BETTER BETTER BETTER BETTER

GI Bleeding EQUAL WORSE WORSE WORSE EQUAL EQUAL BETTER WORSE

BALANCING ACT BETWEEN STROKE RISK

AND BLEEDING RISK

CHADS2-VASC SCORE: STRATIFICATION

OF STROKE RISK

Need to calculate for every patient because the score should

determine your therapy for stroke/systemic embolism reduction.

CHA2DS2-VASc SCORE

0 - No anti-thrombotic therapy

1 - No therapy, ASA, or oral anticoagulation

2 or more - oral anticoagulation

The median practice rate for oral anticoagulant prescription for CHA2DS2-

VASC score ≥2 patient cohort is only 63.3%.

So, up to 2/5 HIGH-RISK patients that SHOULD be receiving anticoagulation

are receiving either antiplatelet agents or nothing

Sometimes patients refuse anticoagulation or have an absolute

contraindication but these situations are uncommon

Usually it is the PROVIDER’S decision to not anticoagulate rather than the

patient’s

Recommend that you refer for a second opinion if you are uncomfortable

with anticoagulating a particular patient

Can always give blood but can’t give back the brain!!

BLEEDING RISK

Both CHADS2-VASC and HAS-BLED

scores predict risk of bleeding

Higher scores=higher bleeding risk

Need to consider patient benefit vs

risk when prescribing anticoagulation

Inform patient of their individual risk

Once again, recommend erring on

side of protecting the brain!!

LEFT ATRIAL OCCLUSION DEVICE

WATCHMAN device

Positioned to occlude the left atrial appendage so that thrombus cannot exit the appendage and enter the left atrium

Left atrial appendage will thrombose

Effective method to reduce stroke risk in patients that are NOT candidates for anticoagulation

Cannot refer patients just because they “don’t want to take Coumadin”

Several devices and surgical procedures have been and are currently being tested

COMMON QUESTIONS REGARDING

NOACs

What if my patient bleeds?

What is nonvalvular atrial fibrillation?

What do I do if my patient is having

surgery?

NOACS AND REVERSAL AGENTS

Only Dabigatran has a reversal agent

Praxbind ® (idarucizumab) approved October 2015

Achieves complete reversal by 4 hours for 90% of patients

The average wholesale price for a 5 g dose of Praxbind is $3500

Better make sure patient really needs it or you will be answering to the CEO/CFO

Reversal agent (andexanet alfa) for Factor Xa inhibitors is in development

Remember, it will also take several hours to “reverse” Warfarin

If a patient has an ICH, the outcome will likely be catastrophic regardless of

whether a reversal agent is available

People rarely die from a GI bleed or severe epistaxis

Just hold the NOAC because the ½ lives are short and provide supportive care

Does not affect my decision regarding use of NOAC-remember bleeding

safety of agents compared to Warfarin

NOACS and NONVALVULAR ATRIAL

FIBRILLATION

Based on AHA/ACC guidelines, currently refers to atrial fibrillation that

occurs in the absence of:

Mitral stenosis

Mechanical valve replacement

Bioprosthetic valve replacement

Valve repair

Therefore, should NOT use NOACs in these settings

Warfarin recommended

RE-ALIGN TRIAL

DABIGATRAN VS WARFARIN IN SETTING OF

MECHANICAL VALVE

252 patients with mechanical

AVR and/or MVR

Warfarin vs Dabigatran 150-300

mg BID

Trial terminated early due to

significantly higher incidence of

thromboembolism and bleeding

with Dabigatran

AVOID NOACS IN PATIENTS WITH

MECHANICAL HEART VALVES!!!

NOACS and SURGERY

Unlike Warfarin, do not need to hold NOACs for 5-7 before procedure

Much shorter ½ life than Warfarin

Hold NOACS 1-2 days before most surgical procedures

Exception: Hold for up to 5 days if epidural injection is planned

Do not need to bridge with Lovenox/IV Heparin in most circumstances

If any questions, please have conversation with surgeon

Sometimes challenging because the surgeon does not want a bleeding

complication and you don’t want the patient to have a stroke

THANK YOU!

Documents

ATRIAL FIBRILLATION and FLUTTER - Amazon S3...Atrial Fibrillation with Slow VR Just because the ventricular rate is slow, doesn’t mean that it is NOT atrial fibrillation May be due