A Case-Based Approach to Stroke Prevention in Atrial ... · ©2017 MFMER | 3605687-1 Sarah Benak,...

©2017 MFMER | 3605687-1

Sarah Benak, APRN

March 11, 2017

A Case-Based Approach to Stroke Prevention in Atrial Fibrillation

1st Annual Cardiovascular Team Conference

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwj7y_7tqKLSAhVJ_4MKHeNmCgoQjRwIBw&url=http://history.mayoclinic.org/&psig=AFQjCNFfzCpY8_MC3aXehyBe_7a2CpQpBg&ust=1487805310509799

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No disclosures

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Learning Objectives

• 1. Identify the population at risk for atrial fibrillation-related ischemic stroke.

• 2. Use evidence to select appropriate stroke risk reduction strategies for patients with atrial fibrillation.

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Question # 1 Patients with nonvalvular atrial fibrillation, in general, have a 5-fold increased risk of stroke.

A. True.

B. False

A. B.

0%0%

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Assessing Stroke Risk in AF

• Nonvalvular AF associated with a 5 risk of stroke 1

• Risk close to 20 x with mitral stenosis 1

• Risk close to 24% with advanced age 1

• #5 all cause of death 2

www.watchbp.co.uk

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Question # 2 Ischemic stroke can increase the risk for atrial fibrillation.

A. True

B. False

A. B.

0%0%

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AF Stroke Mechanism

STROKE

Aging

Contractile Dysfunction

Structural Remodeling

Systemic Risk Factors Atrial

Fibrillation

Kamel, Okin, Elkind, & Iadecola, 2016

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AF Stroke Mechanism

• Thrombus in left atrial appendage is correlated with increased thromboembolic risk in AF 4, 5

Romero, Cao, Garcia, & Taub, n.d.

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Question # 3 The risk for stroke only becomes significant when AF is sustained >48 hours.

A. True

B. False

A. B.

0%0%

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AF Stroke Mechanism

• Duration of AF

• ASSERT 7- AT ≥ 6 hours = 2.5 x risk

• Treatment Approach of AF

• AFFIRM 8- Rate vs rhythm control = 1% annual risk

• Cardioversion Guidelines 9

• Risk 0-0.9% with vs 4-7% without OAC 10

• >48 hours = OAC x 3 weeks pre vs TEE (+ min. 4 weeks post)

• HRS Ablation Expert Consensus 11

• OAC minimum of 2 months; then based on stroke risk (not presence or absence of AF)

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Question # 4-CASE 49 year old female patient with paroxysmal atrial fibrillation. History of hypertension and diabetes. Structurally normal heart. What is her CHA2DS2-VASc score?

A. 3

B. 4

C. 5

D. 6

A. B. C. D.

0% 0%0%0%

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De Jong, n.d.

CHA2DS2-VASc Score

0 = No treatment

1 = Consider anticoagulation

2 = Anticoagulation

Risk Factors Score

Congestive heart failure 1

Hypertension 1

Age 75 2

Age 65-74 1

Diabetes mellitus 1

Stroke/TIA/

thromboembolism 2

Vascular disease 1

Sex: Female 1

Your score

NOAC or Warfarin reduce stroke risk by ~2/3

CHA2DS2VASc

Score

Adjusted Stroke

Rate (% year)

0 0 %

1 1.3 %

2 2.2 %

3 3.2 %

4 4.0 %

5 6.7 %

6 9.8 %

7 9.6 %

8 6.7 %

9 15.2 %

Compare

to CHADS2

1.9 %

2.8 %

4.0 %

5.9 %

8.5 %

12.5 %

18.2 %

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ACC/AHA/HRS 2014 Guidelines

• Class Ia

• In nonvalvular AF with CHA2DS2-VASc score 2 or greater, OAC recommended: warfarin (A), dabigatran (B), rivaroxaban (B), apixaban (B).

• Treat atrial flutter the same as atrial fibrillation in regards to the use of antithrombotic therapy. (C).

• Class IIa

• For patients with nonvalvular AF & CHA2DS2-VASc of 0, it is reasonable to omit antithrombotic therapy. (B)

• Class IIb

• For patients with nonvalvular AF & CHA2DS2-VASc of 1, no antithrombotic therapy or treatment with an OAC or aspirin may be considered. (C)

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Question # 5-CASE 50 year old male patient who has maintained sinus rhythm for 10 months after ablation. History of hypertrophic cardiomyopathy. What is his CHA2DS2-VASc score?

A. 2 B. 3 C. 4 D. This is a trick

question A. B. C. D.

0% 0%0%0%

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When CHA2DS2-VASc does not apply

• Valvular atrial fibrillation

• Rheumatic heart disease

• Mitral stenosis

• Prosthetic valves

• Hypertrophic cardiomyopathy

degenerating old obstructive

thrombus (arrows) along

both sides of all three cusps

www.Mayoclinic.org

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Question # 6 Elderly patients with atrial fibrillation and a history of GI bleed should not be anticoagulated.

A. True

B. False

A. B.

0%0%

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HAS-BLED Score

• Bleeding risk harder to assess

• Overlap in risk factors

Clinical Characteristic Points

Awarded

Hypertension 1

Abnormal liver function 1

Abnormal renal function 1

Stroke 1

Bleeding 1

Labile INRs 1

Elderly (Age >65) 1

Drugs 1

Alcohol 1

Your score 0

Has Bled Score

Bleeds/100 Patient Years

0 1.13

1 1.02

2 1.88

3 3.74

4 8.70

5 12.50

6 0

7 ---

8 ---

9 ---

Total 1.13

Lip, Halperin, & Lane, 2011

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Question # 7-CASE 70 year old female patient with paroxysmal atrial fibrillation. CHA2DS2-VASc score of 4 for hypertension, age, coronary disease, and gender. She wants to know her options to reduce the risk of stroke. You tell her…

A. She has no real options, she must take warfarin with a goal INR of 2.0-3.0

B. She should take aspirin 325 mg daily if she doesn’t want a bleeding complication.

C. A conversation about the options, risks, and benefits may help inform her decision.

D. Whatever she does, don’t take a NOAC because she’ll certainly bleed to death.

A. B. C. D.

0% 0%0%0%

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Opportunity for Shared Decision Making

Patient values and preferences

Research evidence

Context

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Shared Decision Making

Keeval, 2015

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Which agent to choose?

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1955

Eisenhower received warfarin for coronary event while in office

1944

Warfarin discovered (Wisconsin Alumni Research Fund)

Dabigatran (2010)

Rivaroxaban (2011)

Apixaban (2012)

Edoxaban (2017)

FDA approval of 1st NOAC

2006

Failure of Ximelogatran (hepatotoxicity)

1st NOAC reversal agent

Warfarin Era NOAC Era 2010 2017 1954

Warfarin approved for OAC

Timeline

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Aspirin versus OAC

Hart, Pearce, & Aguilar, 2007

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Warfarin

• Reduce risk of stroke by 2/3 and mortality by ¼ compared with control (aspirin or no therapy)

• Currently only OAC with established safety in AF patients with rheumatic mitral valve disease and/or a mechanical heart valve prosthesis

Hart, Pearce, & Aguilar, 2007

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Trial Data: Stroke or SE

Dabigatran

Rivaroxaban

Apixaban

Edoxaban

Combined (random effects)

0.66 (0.53-0.82) 0.0001

0.88 (0.75-1.03) 0.12

0.80 (0.67-0.95) 0.012

0.88 (0.75-1.02) 0.10

0.81 (0.73-0.91) <0.0001

1.0 0.5 0.75

Favor NOAC Favor Warfarin

Ruff et al., 2014

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Trial Data: Major Bleeding

0.94 (0.82-1.07) 0.34

1.03 (0.90-1.18) 0.72

0.71 (0.61-0.81) <0.001

0.80 (0.71-0.90) 0.0002

0.86 (0.73-1.0) 0.06

Dabigatran

Rivaroxaban

Apixaban

Edoxaban

Combined (random effects)

1.0 0.5 0.75


Ruff et al., 2014

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Trial Data: Intracranial Bleeding

0.40 (0.27-0.60)

0.67 (0.47-0.93)

0.42 (0.30-0.58)

0.47 (0.41-0.55)

0.48 (0.39-0.59) <0.0001

1.0 0.5 0.75

Dabigatran

Rivaroxaban

Apixaban

Edoxaban

Combined


Ruff et al., 2014

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How do the NOACs compare to each other?

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Apixaban vs Rivaroxaban n=6,565 n=6,565

1.21 1.03 1.05 (0.64, 1.72) 0.85

Apixaban vs Dabigatran n=6,542 n=6,542

1.22 1.17 0.82 (0.51, 1.31) 0.41

Effectiveness Primary Outcome (S/SE)

Rivaroxaban vs Dabigatran n=15,787 n=15,787

1.12 1.03 1.00 (0.75, 1.32) 0.99

Favor Rivaroxaban Favor Apixaban

1.0 1.5 2.0 0.5 0.0

Favor Dabigatran Favor Rivaroxaban

Favor Dabigatran Favor Apixaban

Event rate per 100 person-years Hazard ratio (95% CI) P

Noseworthy et al., 2016

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Safety Major Bleeding


3.77 2.58 1.30 (1.10, 1.53) <0.01

Favor Rivaroxaban



2.01 4.55 0.39 (0.28, 0.54) <0.001


2.06 3.25 0.50 (0.36, 0.70) <0.001


1.0 1.5 2.0 0.5 0.0

Favor Dabigatran



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1.0 1.5 2.0 0.5 0.0 2.5 3.0

Safety Intracranial Bleeding


0.53 0.26 1.79 (1.12, 2.86) 0.02

Favor Rivaroxaban



0.25 0.43 0.56 (0.21, 1.45) 0.23


0.25 0.34 0.65 (0.25, 1.65) 0.36


Favor Dabigatran



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Question # 8 Anticoagulants are renally dosed. It is sufficient to evaluate renal function only with initiation of therapy.

A. True

B. False

A. B.

0%0%

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Dose Reduction in Renal Disease

Dose reduction may be considered in patients with concomitant p-glycoprotein and CYP3A4 inhibitors, particularly in the setting of CKD

Apixaban

Age

80 years

Weight

60 kg

Creatinine

1.5 mg/dL

If 2 features If 1 feature

2.5 mg BID 5 mg BID

Dabigatran

CrCl

<15 mL/min

CrCl

15-30 mL/min

CrCl

>30 mL/min

Not

recommended 75 mg BID 150 mg BID

Rivaroxaban

CrCl

<15 mL/min

CrCl

15-50 mL/min

CrCl

>50 mL/min

Not

recommended 15 mg OD 20 mg OD

Edoxaban

CrCl <15 or >95 mL/min

CrCl

15-50 mL/min

CrCl

>50 mL/min

Not

recommended 30 mg OD 60 mg OD

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Warfarin Remains the Drug of Choice for Some Patients

• Mechanical valves (class I)

• Valvular AF (rheumatic mitral stenosis)

• Advanced CKD or HD (class IIa)

• If monitoring needed

• Patient preference/comfort/cost

Class III Harm

• Dabigatran should not be used in AF patients and a mechanical heart valve (B).

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Alternatives to Oral Anticoagulation

• Surgical excision

• AtriClip

• Percutaneous closure

• Watchman

• Amplatzer

• ASO, VSDO, ACP, Amulet

• LARIAT

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AtriClip® LAA Exclusion System with preloaded Gillinov-Cosgrove Clip

The AtriClip LAA Exclusion System is indicated for the

occlusion of the left atrial appendage, under direct

visualization, in conjunction with other open cardiac surgical

procedures.

Direct visualization, in this context, requires that the

surgeon is able to see the heart directly, without assistance

from a camera, endoscope, etc., or any other viewing

technology. This includes procedures performed by

sternotomy (full or partial as well as thoracotomy (single or

multiple).

"AtriClip Pro Device," 2017

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Reddy, Sievert, & Halperin, 2014

Kaplan-Meier Curves for Ischemic Stroke, Cardiovascular Mortality, and All-Cause MortalityHR indicates hazard ratio; RR, rate ratio.

Figure Legend:

Watchman PROTECT-AF Trial

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Question # 9- CASE 78 year old female with permanent atrial fibrillation. CHA2DS2-VASc score of 3 for age and gender. Recent trip and fall resulting in wrist sprain. Tolerating OAC with NOAC but concerned for bleeding risk. You tell her…

A. She is a perfect candidate for a Watchman LAAC device.

B. A Watchman LAAC device will be more likely to prevent a stroke than her current therapy.

C. She does not meet CMS criteria for a Watchman LAAC device.

D. Watchman implants are not done at your facility so she is not a candidate.

A. B. C. D.

0% 0%0%0%

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CMS Watchman Implant Criteria

• CHA2DS2-VASc of ≥ 3 or CHADS2 ≥

• Formal shared decision utilizing an independent, non-interventional physician.

• Suitability for short-term warfarin, but deemed unable to take long-term anticoagulation.

• Procedure must be performed in a hospital with an established structural heart disease or electrophysiology program. Procedure must be performed by an interventional cardiologist, electrophysiologist or cardiovascular surgeon, who must have received formal training by the manufacturer, have performed ≥ 25 transeptal procedures, and continue to perform ≥ 25 transeptal procedures, including 12 of which are LAA occlusion, over a two year period.

• Patient is enrolled, and physicians and hospital participate in a prospective, national, audited registry for at least four years from the time of implantation.

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Key Points

• Risk of stroke in AF is highly influenced by clinical factors

• Engage patients in decision to anticoagulate

• NOACs offer good stroke reduction at lower risk of intracranial bleeding

• LAAC

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References

1. Wolf, P. A., Abbott, R. D., & Kannel, W. B. (1991). Atrial Fibrillation as an Independent Risk Factor for Stroke: The Framingham Study. Stroke, 22, 983-988. https://doi.org/10.1161/01.STR.22.8.983

2. Mozzafarian, D., Benjamin, E. J., Go, A. S., & Arnett, D. K. (2016). Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation, 133(4), e38-360. http://dx.doi.org/10.1161/CIR.0000000000000350

3. Kamel, H., Okin, P. M., Elkind, M. S.V., & Iadecola, C. (2016). Atrial fibrillation and mechanisms of stroke; Time for a new model. Stroke, 48(3), 1-7. http://dx.doi.org/10.1161/STROKEAHA.115.012004

4. Chimowitz, M. I., DeGeorgia, M. A., Poole, R. M., Hepner, A., & Armstrong, W. M. (1993). Left atrial spontaneous echo contrast is highly associated with previous stroke in patients with atrial fibrillation or mitral stenosis. Stroke, 24, 1015-1019. http://dx.doi.org/10.1161/01.STR.24.7.1015

5. Zabalgoitia, M., Halperin, J., Pearce, L., Blackshear, J., Asinger, R. W., & Hart, R. G. (1998). Trasnesophageal echocardiographic correlates of clinical risk of thromboembolism in nonvalvular atrial fibrillaiton. Journal of the American College of Cardiology, 31, 1622-1666.

6. Romero, J., Cao, J. J., Garcia, M., & Taub, C. (n.d.). Cardiac imaging for assessment of left atrial appendage stasis and thrombosis. Retrieved from Nature Reviews Cardiology website: http://www.nature.com/nrcardio/journal/v11/n8/full/nrcardio.2014.77.html

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References 7. Healey, J. S., Connolly, S. J., Gold, M. R., Israel, C. W., Van Gelder, I. C., Capucci, A., . . . Hohnloser, S. (2012). Subclinical atrial fibrillation and the risk of stroke. The New England Journal of Medicine, 366, 120-129. http://dx.doi.org/10.1056/NEJMoa1105575

8. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. (2002). A comparison of rate control and rhythm control in patients with atrial fibrillation [Advertisement]. The New England Journal of Medicine, 347(23), 1825-1833.

9. Writing Committee Members, & ACC/AHA Task Force Members. (2014). 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Circulation, 130, e199-e267. http://dx.doi.org/10.111/CIRC.0000000000000041

10. Gentile, F., Elhendy, A., Khandheria, B. K., Seward, J. B., Lohse, C. M., Shen, W.-K., . . . Jamil Tajik, A. (2002). Safety of electrical cardioversion in patients with atrial fibrillation. Mayo Clinic Proceedings, 77(9), 897-904. http://dx.doi.org/10.4065/77.9.897

11. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: Recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design (HRS/EHRA/ECAS, Comp.). (2012). Heart Rhythm Society.

12. De Jong, J. (Ed.). (n.d.). Chadsvasc.org/. Retrieved from http://chadsvasc.org/

13. Nishimura, R. A., Otto, C. M., & Writing Committee Members. (2014). 2014 ACC/AHA guideline for the management of patients with valvular heart disease. Circulation. http://dx.doi.org/10.1161/CIR.0000000000000031

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References 14. Lip, G. Y., Halperin, J. L., & Lane, D. A. (2011). Comparitive validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED score. The Journal of the American College of Cardiology, 11(57), 173-180. http://dx.doi.org/10.1016/j.jacc.2010.09.024

15. Keeval, J. (Ed.). (2015). Health Decision. Retrieved March 5, 2017, from https://www.healthdecision.org/tool.html#/tool/afib

16. Hart, R. G., Pearce, L. A., & Aguilar, M. I. (2007). Meta-analysis antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillaiton. Annals of Internal Medicine, 146(12), 857-867.

17. Connolly, S. J., Ezekowitz, M. D., Phil, D., Yusuf, S., Eikelboom, J., & Oldgren, J. (2009). Dabigatran versus warfarin in patients with atrial fibrillation. The New England Journal of Medicine, 361, 1139-1151. http://dx.doi.org/10.1056/NEJMoa0905561

18. Patel, M. R., Mahaffey, K. W., Garg, J., Guohua Pan, M. S., Singer, D. E., & The ROCKET AF Steering Committee. (2011). Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. The New England Journal of Medicine, 365, 883-891. http://dx.doi.org/10.1056NEJMoa1009638

19. Granger, C. B., Alexander, J. H., McMurray, J. J.V., Lopez, R. D., Hylek, E. M., & The ARISTOTLE Committees and Investigators. (2011). Apixaban versus warfarin in patients with atrial fibrillation. The New England Journal of Medicine, 365, 981-992. http://dx.doi.org/10.1056/NEJMoa1107039

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References 20. The ENGAGE AF-TIMI 48 Investigators. (2013). Edoxaban versus warfarin in patients with atrial fibrillation. The New England Journal of Medicine, 369, 2093-2104. http://dx.doi.org/10.1056/NEJMoa1210907

21. Ruff, C. T., Giugliano, R. P., Braunwald, E., Hoffman, E. B., Deenadayalu, N., Ezekowitz, M. D., . . . Antman, E. M. (2014). Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: A meta-analysis of randomised trials. The Lancet, 383(9921), 955-962. http://dx.doi.org/10.1016/S0140-6736(13)62343-0

22. Noseworthy, P. A., Yao, X., Abraham, N. S., Sangaralingham, L. R., McBane, R. D., & Shah, N. D. (2016). Direct comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in nonvalvular atrial fibrillation. Chest, 150(6), 1302-1312. http://dx.doi.org/10.1017/j.chest.2016.07.013

23. AtriClip pro device. (2017). Retrieved March 5, 2017, from https://www.atricure.com/atrial-occlusion/atriclip-pro

24. Reddy, V. Y., Sievert, H., & Halperin, J. (2014). Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: A randomized clinical trial. The Journal of the American Medical Association, 312(19), 1988-1998. http://dx.doi.org/10.1001/jama.2014.15192

25. Holmes, D. R., Doshi, S. K., Kar, S., Price, M. J., Sanchez, J. M., Sievert, H., . . . Reddy, V. Y. (2015). Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation. The Journal of The American College of Cardiology, 65(24), 2614-2623. http://dx.doi.org/10.1016/j.jacc.2015.04.025

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References

26. Holmes, D. R., Kar, S., Price, M. J., Whisenant, B., Sievert, H., Doshi, S. K., . . . Reddy, V. Y. (2014). Prospective randomized evaluation of the Watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: The PREVAIL trial. The Journal of the American College of Cardiology, 64(1), 1-12. http://dx.doi.org/10.1016.jacc.2014.04.029

27. Use of LARIAT Suture Delivery Device for Left Atrial Appendage Closure: FDA Safety Communication. (2015, July 3). Retrieved March 5, 2017, from U.S. Food and Drug Administration website: https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm454501.htm

28. ACC/HRS/SCAI. (2015). 2015 ACC/HRS/SCAI left atrial appendage occlusion device societal overview.

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