1. Which NOAC and When for Stroke Prevention in AF?
Elaine M. Hylek MD MPH
Boston University School of Medicine
Professor of Medicine

2. Disclosures Research support Executive Steering Committees:
BMS/Pfizer-ARISTOTLE trial;
Janssen-ORBIT-AF Registry, QUANTUM AF;
Boehringer Ingelheim-REVERSE-AD
Consultant
Bayer, Boehringer Ingelheim, BMS/Pfizer, Janssen, Medtronic, Portola, Roche
Honoraria
Boehringer Ingelheim, BMS/Pfizer
Other
Steering Committee American College of Cardiology/Medscape Center of Excellence on Atrial Fibrillation;
HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation

3. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation.
Published on January 28, 2019, available at: Journal of the American College of Cardiology and Circulation.
The full-text guidelines are also available on the following Web sites: ACC ( and AHA(professional.heart.org)

5. Anticoagulation Regimen – Balancing Risks and Benefits
Recommendations for Selecting an Anticoagulant Regimen—Balancing Risks and Benefits
COR
LOE
Recommendations I A
For patients with AF and an elevated CHA2DS2-VASc score of 2 or greater in men or 3 or greater in women, oral anticoagulants are recommended.
Options include:
Warfarin (LOE: A)
Dabigatran (LOE: B)
Rivaroxaban (LOE: B)
Apixaban (LOE: B) or
Edoxaban (LOE: B-R)
MODIFIED: This recommendation has been updated in response to the approval of edoxaban, a new factor Xa inhibitor. More precision in the use of CHA2DS2-VASc scores is specified in subsequent recommendations. The LOEs for warfarin, dabigatran, rivaroxaban, and apixaban have not been updated for greater granularity as per the new LOE system. (Section 4.1. in the 2014 AF Guideline) The original text can be found in Section 4.1 of the 2014 AF guideline. Additional information about the comparative effectiveness and bleeding risk of NOACs can be found in Section B
B-R

6. Anticoagulation Regimen – Balancing Risks and Benefits
Recommendations for Selecting an Anticoagulant Regimen—Balancing Risks and Benefits
COR
LOE
Recommendations I
B-NR
Renal function and hepatic function should be evaluated before initiation of a NOAC and should be reevaluated at least annually.
MODIFIED: Evaluation of hepatic function was added. LOE was updated from B to B-NR. New evidence was added. (Section 4.1. in the 2014 AF Guideline)

7. Reversal COR LOE Recommendations I B-NR
Idarucizumab is recommended for the reversal of dabigatran in the event of life-threatening bleeding or an urgent procedure.
NEW: New evidence has been published about idarucizumab to support LOE B-NR.
IIa
Andexanet alfa can be useful for the reversal of rivaroxaban and apixaban in the event of life-threatening or uncontrolled bleeding.
NEW: New evidence has been published about andexanet alfa to support LOE B-NR.

9. METHODS
Retrospective new-user cohort study of US Medicare patients with AF using claims data
Warfarin (n=183,318), or a standard dose of dabigatran (150 mg twice-daily; n=86,198), rivaroxaban (20 mg once-daily; n=106,389) or apixaban (5 mg twice-daily; n=73,039)
Anticoagulation exposure: censored with >3-day gap in Rx
Study Period: October 2010 and September 2015
Propensity score adjusted Cox proportional hazards regression to estimate adjusted HR 95% (CI) for TE stroke, ICH, major extracranial bleeding, and all-cause mortality, comparing each NOAC with warfarin, and with each other NOAC

10. >65 years of age

11. Retrospective cohort study of Medicare beneficiaries included in the
U.S. Renal Data System (October 2010 to December 2015).
Eligible patients: ESKD and AF undergoing dialysis who initiated Rx with OAC. (Outcomes were only assessed in patients treated with apixaban or warfarin).

12. 2,351 patients on apixaban: 44% FDA dose 5 mg twice daily
23 ,172 patients on warfarin
In matched cohorts 1:3, there was no difference in the risks of stroke/systemic embolism between apixaban and warfarin (HR, 0.88; 95% CI, 0.69–1.12; P=0.29)
Stroke/SEE Death
Apixaban 5 mg
vs mg HR, 0.61; 95% CI, 0.37–0.98 HR, 0.64; 95% CI, 0.45–0.92
vs warfarin HR, 0.64; 95% CI, 0.42–0.97 HR, 0.63; 95% CI, 0.46–0.85

13. MAJOR BLEEDING NO DIFFERENCE in INTRACRANIAL OR GI BLEEDING
Absolute rates of major bleeding higher than previously reported in this patient population—19.7% for apixaban and 22.9% for warfarin (? related to definition)
High discontinuation rates for both drugs apixaban 105 days, warfarin 157 days
Apixaban was associated with a significantly lower risk of major bleeding (HR, 0.72; 95% CI, 0.59–0.87; P<0.001).
NO DIFFERENCE in INTRACRANIAL OR GI BLEEDING

15. 352 patients, mean age 77 years (apixaban or rivaroxaban)
February 7, 2019.
DOI:
/NEJMoa
352 patients, mean age 77 years (apixaban or rivaroxaban)
ICH [64%] or GI [26%]
Low or High bolus followed by 2 hour infusion:
92% reduction anti–factor Xa activity
Excellent or good hemostasis occurred in 82% who could be evaluated.
Within 30 days, death occurred in 49 patients (14%) and a thrombotic event in 34 (10%).
SURGICAL patients were not studied
Recurrence of activity at end of infusion
Approx cost US $25K-50K

16. CONCLUSIONS NOACs preferred over warfarin for stroke prevention in AF
AC recommended for CHA2DS2-VASc ≧2 for men; ≧3 for women
Warfarin first line Rx for mechanical valves, mod-severe mitral stenosis
To date, limited evidence for use of either VKA or apixaban in ESRD
Sequelae of reversal in clinical practice warrants further study