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Afternoon Report
PETER VAYALIL
Case Presentation
•63 y/o female with history of DM2, morbid obesity, COPD,
and likely sleep apnea presented with significant tissue
necrosis/gangrene with crepitus on the right foot extending
up the right lower extremity
•She was taken to the OR emergently for an AKA of the right
lower extremity
•Intraoperatively, she developed hypotension and
tachycardia requiring pressors
Case Presentation
•Was stabilized after surgery and weaned off pressors
over the next few days
•IV abx for bacteremia
•She went on to have an extensive ICU stay requiring
multiple days on the ventilator
•Her condition slowly improved
TEE
•Normal LVEF
•A large vegetation was noted on the posterior mitral leaflet.
•There is trace MR and TR.
•There is aortic sclerosis with mild stenosis.
•There was no left atrial appendage thrombus.
Valvular atrial fibrillation
Nonvalvular vs valvular atrial fibrillation
Types of A Fib
Type
Definition
Paroxysmal AF
• AF that terminates spontaneously or with intervention within
7 d of onset. • Episodes may recur with variable frequency.
Persistent AF
Continuous AF that is sustained >7 d.
Longstanding persistent AF
• Continuous AF of >12 mo duration.
Permanent AF
Permanent AF is used when there has been a joint decision by
the patient and clinician to cease further attempts to restore
and/or maintain sinus rhythm. • Acceptance of AF represents a
therapeutic attitude on the part of the patient and clinician
rather than an inherent pathophysiological attribute of the AF. •
Acceptance of AF may change as symptoms, the efficacy of
therapeutic interventions, and patient and clinician preferences
evolve.
Nonvalvular AF
AF in the absence of rheumatic mitral stenosis, a mechanical or
bioprosthetic heart valve, or mitral valve repair.
Valvular A Fib
•Mitral regurgitation
•Mitral stenosis
•Mitral valve prolapse
•Hypertrophic cardiomyopathy
•Mechanical Prosthetic valves
Not Valvular A Fib
•Aortic stenosis
•Tricuspid regurgitation
•Bioprosthetic heart valve
•Valve repair
Anticouglation
Different Guidelines
•Higher risk and different mechanism of thrombosis
•Lack of sufficient data on the efficacy of NOACs for valvular A Fib
•Mitral stenosis, essentially on a rheumatic basis, is the form of AF
with native valves with the highest risk of thromboembolism
• Probably related to the low-flow patterns occurring in the left
atrium in such a condition
• Nonvalvular AF increases the risk of stroke 5 times and AF in the
setting of mitral stenosis increases the risk of stroke 20 times
Studies
RE-LY trial testing two doses of dabigatran etexilate vs warfarin, “history of heart valve disorders (i.e.
prosthetic valve or hemodynamically relevant valve disease) were exclusion criteria
ROCKET-AF trial, testing rivaroxaban against warfarin, excluded only hemodynamically significant mitral
valve stenosis, and prosthetic heart valves, but permitted the inclusion of patients with diseases in native
valves other than the mitral valve, as well as of patients treated with annuloplasty, commisurotomy or
other valvuloplasty
AVERROES trial, testing apixaban vs warfarin in patients considered “unsuitable” to VKAs, the exclusion
criterion was “valvular disease requiring surgery”
ARISTOTLE, testing apixaban vs warfarin, the study design 67, 68 only excluded “clinically significant
(moderate or severe) mitral stenosis”, as well as “conditions other than AF that require chronic
anticoagulation (e.g., prosthetic mechanical heart valve)”
ENGAGE-AF study, which tested two exposure strategies of edoxaban vs warfarin, patients with “moderate
or severe mitral stenosis, unresected atrial myxoma, or a mechanical heart valve” were excluded and
subjects with bioprosthetic heart valves and/or valve repair were allowed
2014 AHA/ACC/HRS Atrial Fibrillation
Guideline
In patients with AF, antithrombotic therapy should be individualized based on shared
decisionmaking after discussion of the absolute and RRs of stroke and bleeding, and the
patient’s values and preferences.
Selection of antithrombotic therapy should be based on the risk of thromboembolism
irrespective of whether the AF pattern is paroxysmal, persistent, or permanent
For patients with nonvalvular AF with prior stroke, transient ischemic attack (TIA), or a
CHA2DS2-VASc score of 2 or greater, oral anticoagulants are recommended. Options include:
warfarin (INR 2.0 to 3.0) (Level of Evidence: A), dabigatran (Level of Evidence: B), rivaroxaban
(Level of Evidence: B), or apixaban
For patients with AF who have mechanical heart valves, warfarin is recommended and the target
international normalized ratio (INR) intensity (2.0 to 3.0 or 2.5 to 3.5) should be based on the
type and location of the prosthesis
Which NOAC to Choose???
Comparison of NOACs
Safety outcomes of NOACs vs. warfarin
Direct Comparison vs Warfarin - retrospective
analysis using insurance database
•Stroke or systemic embolism
• apixaban was associated with lower risk (hazard ratio [HR] 0.67, 95% CI 0.46–0.98, P=0.04)
• dabigatran and rivaroxaban were associated with a similar risk (dabigatran: HR 0.98, 95% CI 0.76–
1.26, P=0.98; rivaroxaban: HR 0.93, 95% CI 0.72–1.19,P=0.56).
•For major bleeding, apixaban and dabigatran were associated with lower risk
(apixaban: HR 0.45, 95% CI 0.34–0.59, P<0.001; dabigatran: HR 0.79, 95% CI 0.67–0.94,P<0.01),
and rivaroxaban was associated with a similar risk (HR 1.04, 95% CI 0.90–1.20],P=0.60).
•All non–vitamin K antagonist oral anticoagulants were associated with a lower risk of intracranial
bleeding.
Direct Comparison vs Each Other
•No differences between the three NOACs in the risk of stroke or systemic embolism
• (hazard ratio [HR]: 1.00 [0.75, 1.32] for rivaroxaban versus dabigatran; 0.82 [0.51, 1.31] for apixaban
versus dabigatran; and 1.05 [0.64, 1.72] for apixaban versus rivaroxaban)
•Apixaban was associated with lower major bleeding risk (HR 0.50 [0.36, 0.70], p<0.001 versus
dabigatran; and 0.39 [0.28, 0.54], p<0.001 versus rivaroxaban).
•Rivaroxaban was associated with increased risk of major bleeding (HR 1.30 [1.10, 1.53], p<0.01)
and intracranial bleeding (HR 1.79 [1.12, 2.86], p<0.05) compared to dabigatran
Direct comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in non-valvular atrial fibrillation
Peter A. Noseworthy, MD; Xiaoxi Yao, PhD; Neena S. Abraham, MD, MSCE; Lindsey R. Sangaralingham, MPH; Robert D. McBane, MD; Nilay D. Shah, PhD
A= Apixaban, D=dabigatran, E= edoxaban, R=rivaroxaban
NOAC Reversal
October, 2016
◦ Idarucizumab – antidote for direct thrombin inhibitors
Andexanet alfa - Factor Xa inhibitors
A 75-year-old woman is evaluated during a follow-up visit for recently diagnosed
atrial fibrillation that is adequately rate controlled on medication. Medical history
is significant for hypertension and end-stage kidney disease; she is on
hemodialysis. Medications are metoprolol, digoxin, lisinopril, and amlodipine.
She has not yet been started on stroke prevention therapy.
On physical examination, temperature is 36.8 °C (98.2 °F), blood pressure is
120/65 mm Hg, pulse rate is 72/min, and respiration rate is 16/min. BMI is 29.
The precordial cadence is irregularly irregular. There is no evidence of pulmonary
or peripheral congestion.
Which of the following is the most appropriate treatment?
•Apixaban
•Aspirin and clopidogrel
•Dabigatran
•Dose-adjusted warfarin
•Rivaroxaban
•More than one choice is appropriate
85 -year-old-woman with hypertension and diabetes is admitted for upper GI bleed.
She has had a long history of severe GERD refractory to treatment. During the course
of admission, she is found to be in Atrial Fibrillation. An echocardiogram performed
showed moderate stenosis of her bio prosthetic aortic valve with otherwise normal
functioning. She is started on metoprolol to help control her heart rates. Her GI bleed
was appropriately treated.
Which of the following is the most appropriate treatment choice in terms of anticoagulation for
her?
•Apixaban
•Aspirin
•Dabigatran
•Dose-adjusted warfarin
•Rivaroxaban
•More than one choice is appropriate
•No anticoagulation
Any Questions?