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 TypeDefinition Paroxysmal AF AF that terminates spontaneously or with intervention within 7 d of onset. Episodes may recur with variable frequency. Persistent AFContinuous AF that is sustained >7 d. Longstanding persistent AF Continuous AF of >12 mo duration. Permanent AFPermanent 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 AFAF 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 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 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 vs Each Other

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?