ATRIAL FIBRILLATION and FLUTTER - Amazon S3...Atrial Fibrillation with Slow VR Just because the...
Transcript of ATRIAL FIBRILLATION and FLUTTER - Amazon S3...Atrial Fibrillation with Slow VR Just because the...
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)
Approved by FDA in 2011
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
No need to monitor INR
No common significant drug interactions
Patients can eat veggies
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
WHAT TO TELL PATIENTS
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)
Approved by FDA in 2012
Factor Xa inhibitor
Half-life 9-14 hours
BID dosing
No need to monitor INR
No common significant drug interactions
Patients can eat veggies
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
WHAT TO TELL PATIENTS
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)
Approved by FDA in 2015
Factor Xa inhibitor
Half-life of 10-14 hours
QDAY dosing
No need to monitor INR
No common significant drug interactions
Patients can eat veggies
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
WHAT TO TELL PATIENTS
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!