A Case-Based Approach to Stroke Prevention in Atrial ... · ©2017 MFMER | 3605687-1 Sarah Benak,...
Transcript of 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
©2017 MFMER | 3605687-3
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.
©2017 MFMER | 3605687-4
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%
©2017 MFMER | 3605687-5
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
©2017 MFMER | 3605687-6
Question # 2 Ischemic stroke can increase the risk for atrial fibrillation.
A. True
B. False
A. B.
0%0%
©2017 MFMER | 3605687-7
AF Stroke Mechanism
STROKE
Aging
Contractile Dysfunction
Structural Remodeling
Systemic Risk Factors Atrial
Fibrillation
Kamel, Okin, Elkind, & Iadecola, 2016
©2017 MFMER | 3605687-8
AF Stroke Mechanism
• Thrombus in left atrial appendage is correlated with increased thromboembolic risk in AF 4, 5
Romero, Cao, Garcia, & Taub, n.d.
©2017 MFMER | 3605687-9
Question # 3 The risk for stroke only becomes significant when AF is sustained >48 hours.
A. True
B. False
A. B.
0%0%
©2017 MFMER | 3605687-10
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)
©2017 MFMER | 3605687-11
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%
©2017 MFMER | 3605687-12
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 %
©2017 MFMER | 3605687-13
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)
©2017 MFMER | 3605687-14
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%
©2017 MFMER | 3605687-15
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
©2017 MFMER | 3605687-16
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%
©2017 MFMER | 3605687-17
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
©2017 MFMER | 3605687-18
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%
©2017 MFMER | 3605687-19
Opportunity for Shared Decision Making
Patient values and preferences
Research evidence
Context
©2017 MFMER | 3605687-22
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
©2017 MFMER | 3605687-24
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
©2017 MFMER | 3605687-26
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
©2017 MFMER | 3605687-27
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
Favor NOAC Favor Warfarin
Ruff et al., 2014
©2017 MFMER | 3605687-28
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
Favor NOAC Favor Warfarin
Ruff et al., 2014
©2017 MFMER | 3605687-30
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
©2017 MFMER | 3605687-31
Safety Major Bleeding
Rivaroxaban vs Dabigatran n=15,787 n=15,787
3.77 2.58 1.30 (1.10, 1.53) <0.01
Favor Rivaroxaban
Event rate per 100 person-years Hazard ratio (95% CI) P
Apixaban vs Rivaroxaban n=6,565 n=6,565
2.01 4.55 0.39 (0.28, 0.54) <0.001
Apixaban vs Dabigatran n=6,542 n=6,542
2.06 3.25 0.50 (0.36, 0.70) <0.001
Favor Rivaroxaban Favor Apixaban
1.0 1.5 2.0 0.5 0.0
Favor Dabigatran
Favor Dabigatran Favor Apixaban
Noseworthy et al., 2016
©2017 MFMER | 3605687-32
1.0 1.5 2.0 0.5 0.0 2.5 3.0
Safety Intracranial Bleeding
Rivaroxaban vs Dabigatran n=15,787 n=15,787
0.53 0.26 1.79 (1.12, 2.86) 0.02
Favor Rivaroxaban
Event rate per 100 person-years Hazard ratio (95% CI) P
Apixaban vs Rivaroxaban n=6,565 n=6,565
0.25 0.43 0.56 (0.21, 1.45) 0.23
Apixaban vs Dabigatran n=6,542 n=6,542
0.25 0.34 0.65 (0.25, 1.65) 0.36
Favor Rivaroxaban Favor Apixaban
Favor Dabigatran
Favor Dabigatran Favor Apixaban
Noseworthy et al., 2016
©2017 MFMER | 3605687-33
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%
©2017 MFMER | 3605687-34
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
©2017 MFMER | 3605687-35
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).
©2017 MFMER | 3605687-36
Alternatives to Oral Anticoagulation
• Surgical excision
• AtriClip
• Percutaneous closure
• Watchman
• Amplatzer
• ASO, VSDO, ACP, Amulet
• LARIAT
©2017 MFMER | 3605687-37
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
©2017 MFMER | 3605687-38
Alternatives to OAC
• Surgical excision
• AtriClip
• Percutaneous closure
• Watchman
• Amplatzer
• ASO, VSDO, ACP, Amulet
• LARIAT
©2017 MFMER | 3605687-40
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
©2017 MFMER | 3605687-43
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%
©2017 MFMER | 3605687-44
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.
©2017 MFMER | 3605687-45
Alternatives to OAC
• Surgical excision
• AtriClip
• Percutaneous closure
• Watchman
• Amplatzer
• ASO, VSDO, ACP, Amulet
• LARIAT
©2017 MFMER | 3605687-46
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
©2017 MFMER | 3605687-48
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
©2017 MFMER | 3605687-49
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
©2017 MFMER | 3605687-50
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
©2017 MFMER | 3605687-51
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
©2017 MFMER | 3605687-52
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.