1. The Effect of CMS Criteria on the Patient Population Selected to Receive the WATCHMAN™ Procedure
Cara Coffelt, PharmD
PGY-1 Pharmacy Resident
St. Joseph’s/Candler Health System
Co-Investigators:
Ashley Woodhouse, PharmD, BCACP, CACP, CDTM
Hannah Brockman, PharmD Candidate

2. Disclosure Statement
Disclosure statement: these individuals have the following to disclose concerning possible personal or financial relationships with commercial entities (or their competitors) that may be referenced in this presentation
Cara Coffelt, PharmD: nothing to disclose
Ashley Woodhouse, PharmD, BCACP, CACP, CDTM: nothing to disclose
Hannah Brockman, PharmD Candidate: nothing to disclose

3. Background WATCHMAN™ Procedure
Performed in patients with atrial fibrillation
Provides closure of the atrial appendage
Also called left atrial appendage closure (LAAC)
Reddy VY, et al. JAMA ;312(19):
Reddy VY, et al. Circulation. 2013; 127:
WatchmanDevice.com

4. Background
Removes the need for long-term anticoagulation for stroke prevention in atrial fibrillation patients
~45 days post operatively
Reddy VY, et al. JAMA ;312(19):
Reddy VY, et al. Circulation. 2013; 127:

5. Background
PROTECT AF
Efficacy and safety of the device in comparison to warfarin treated patients
Evaluated rates of strokes/TIAs
Evaluated cardiovascular (CV) and overall mortality
Mean follow up 3.8 years
Reddy VY, et al. JAMA ;312(19):
Reddy VY, et al. Circulation. 2013; 127:

6. Background
PROTECT AF
Composite efficacy endpoint: stroke, systemic embolism, and cardiovascular/unexplained death
Primary event rate 8.4% in the device group vs. 13.9% in the warfarin group
Meeting criteria for both noninferiority (posterior probability >99.9%) and superiority (posterior probability 96.0%)
Lower CV mortality rates in the device group (3.7% vs. 9.0%) [HR 0.40; 95% CI, ;(P = 0.005)]
Lower all-cause mortality in the device group (12.3% vs. 18.0%) [HR 0.66; 95%CI, ;(P = 0.04)]
In Bayesian statistics, the posterior probability of a random event or an uncertain proposition is the conditional probability that is assigned after the relevant evidence or background is taken into account.
Ischemic strokes did not differ between the two groups (5.2% vs 4.21%; RR 1.26; CI ), but hemorrhagic and disabling strokes favored the device group
Mortality outcome driven by death by hemorrhagic stroke
No difference in mortality by ischemic strokes
Reddy VY, et al. JAMA ;312(19):
Reddy VY, et al. Circulation. 2013; 127:

7. Background Stroke Risk Stratification in Atrial Fibrillation
CHADS2 or CHA2DS2-VASc score
Determines annual stroke risk
Score ≥ 2: anticoagulation therapy warranted
Cage BF, et al. JAMA 2001;285(22):

8. Background Patient Population
PROTECT AF trial: 34% of patients in the device group had a CHADS2 of 1 (or CHA2DS2-VASc of 2)
CHADS2 of 1 represents ~2.8% risk
CHADS2 of 2 represents ~4% risk .
Cage BF, et al. JAMA 2001;285(22):

9. Background CMS Criteria Additional CMS Criteria
Restricts the patient population that would be eligible for reimbursement of the WATCHMAN™ procedure
CHADS2 ≥ 2 or CHA2DS2-VASc ≥ 3
Those at a lower risk of stroke excluded from eligibility
Additional CMS Criteria
Suitability for short-term warfarin
but deemed unable to take long term oral anticoagulation
. CMM. Final Decision Memorandum for Percutaneous Left Atrial Appendage Closure (LAAC).
Cage BF, et al. JAMA 2001;285(22): .

10. Study Objectives Primary objectives Secondary objectives
To determine if the selected patient population, based on their CHADS2 or CHA2DS2-VASc score, differs from the population originally studied for safety and efficacy in the PROTECT AF trial
Secondary objectives
To evaluate the effect of the WATCHMAN™ procedure on rates of thromboembolism and major bleeding within the follow-up period

11. Study Center St. Joseph’s/Candler Health System
Community health system with 714 beds divided between two anchor hospitals
WATCHMAN™ procedure is performed at St. Joseph’s Hospital

12. Methods Study design Population
Retrospective, observational investigation
Approved by the St. Joseph’s/Candler Institutional Review Board
Population
Adult patients with atrial fibrillation who have undergone the WATCHMAN™ procedure at St. Joseph’s Hospital
Adult patients included in the WATCHMAN™ device group in the PROTECT AF trial

13. Methods: Inclusion Exclusion None
Prior history of the WATCHMAN™ procedure
None
Reddy VY, et al. JAMA ;312(19):
Reddy VY, et al. Circulation. 2013; 127:

14. Methods Data Collection: Patient demographics
CHADS2/CHA2DS2-VASc score
HAS-BLED score
INRs prior to and after procedure on warfarin therapy
Duration of anticoagulant therapy before and after procedure
Thromboembolisms (ischemic stroke/TIA)
Major Bleeds
Insurance Provider
HAS-BLED is a scoring system developed to assess 1-year risk of major bleeding in patients with atrial fibrillation
The HAS-BLED mnemonic stands for:
Hypertension
Abnormal renal and liver function (1 pt each)
Stroke
Bleeding
Labile INRs
Elderly
Drugs or alcohol (1 pt each)
The new ESC guidelines on atrial fibrillation recommend assessment of bleeding risk in AF using the HAS-BLED bleeding risk schema as a simple, easy calculation,[1][3] whereby a score of ≥3 indicates "high risk" and some caution and regular review of the patient is needed.[4] The HAS-BLED score has also been validated in an anticoagulated trial cohort of 7329 patients with AF - in this study, the HAS-BLED score offered some improvement in predictive capability for bleeding risk over previously published bleeding risk assessment schemas and was simpler to apply

15. Methods Outcome variables Primary Secondary CHADS2 score (0-6)
CHA2DS2-VASc (0-9)
Thromboembolism (Ischemic stroke and TIA)
Major bleed (intracranial, GI, or any bleed requiring transfusion)

16. Methods Treatment groups
Patients with atrial fibrillation who have undergone the WATCHMAN™ procedure at St. Joseph’s Hospital
PROTECT AF trial participants included in the WATCHMAN™ device arm
463 patients
Reddy VY, et al. JAMA ;312(19):
Reddy VY, et al. Circulation. 2013; 127:

17. Methods Data analysis Chi-square test for categorical data
CHADS2/CHA2DS2-VASc
Thromboembolisms
Major Bleeds
P-value <0.05 was considered significant

18. Results: Demographics and Clinical Characteristics
SJC Patients (n=32)
PROTECT AF (n=463)
P-value
Age, years ± SD
73.9 ± 5.8
71.7 ± 8.8 -
Females, no. (%)
15 (46.9)
137 (29.6)
0.04
Age ≥ 75y, no. (%)
20 (62.5)
190 (41)
0.017
Paroxysmal, no. (%)
19 (59.4)
200 (43.2)
0.075
Persistent, no. (%)
8 (25)
97 (21)
0.59
Permanent, no. (%)
2 (6.3)
160 (34.6)
0.001
Unknown, no. (%)
3 (9.4)
6 (1.3)
0.003
SD = standard deviation
SJC = St. Joseph’s/Candler

19. Results: Descriptive Data
SJC (n=32)
CHA2DS2-VASc Score ± SD
3.78 ± 1.4
HAS-BLED ± SD
1.75 ± 0.9
*Not reported in PROTECT AF

20. Results: Primary Outcome
Percent
34%
32%
CHADS2 Score

21. Results: Secondary Outcomes6% 5%
4.8% 3%
1 stroke, 2 GI bleeds
Stroke- implant 1/12, stroke on 1/21
On coumadin at the time of stroke INR 2.1
Bleed- watchman 7/14, bleed on 7/19 and again on 7/27 INR 3.2 and 1.5 respectively. Still on coumadin. HAS-BLED 1
Bleed #2- watchman 11/17, coumadin on board 11/24 bleed INR had 2 GI bleeds HAS-BLED 4

22. Discussion
Number of patients who had a CHADS2 score of 1 were lower in the SJC group in comparison to the PROTECT AF device group
The risk factor of age ≥ 75 years old, which represented a larger amount of the SJC population, may have contributed to higher CHADS2 scores observed

23. Discussion Safety and Efficacy:
One stroke observed in a patient still on warfarin therapy (INR 2.1)
Two GI bleeds observed in patients with supratherapeutic INRs

24. Discussion Strength Limitations
Study to evaluate CMS influence on clinically important outcomes
Ability to collect additional data beyond the information provided in PROTECT AF, including CHA2DS2-VASc scores
Limitations
Small, retrospective study limits generalizability
Patient follow-up was limited
Limitation of comparison: PROTECT AF intention to treat

25. Conclusions
CMS criteria appears to have an impact on the patient population selected for the WATCHMAN™ procedure, by excluding those atrial fibrillation patients who are at a lower risk of having a stroke according to CHADS2
Even though there is a shift in population, there appears to be no difference in the rates of thromboembolisms or major bleeding
Extended follow-up is needed to determine the effect on mortality

26. Acknowledgements Ashley Woodhouse, PharmD, BCACP, CACP, CDTM
Hannah Brockman, PharmD Candidate

27. Self-assessment Question
Purpose
Define CHADS2 and CHA2DS2-VASc scores and their associated pharmacological intervention appropriate for stroke prevention in atrial fibrillation.
Self-assessment Question
At what CHADS2 or CHA2DS2-VASc score is anticoagulation warranted for stroke prevention in atrial fibrillation?
≥ 2

28. References
1. Cage BF, Waterman AD, Shannon W, et al. Validation of Clinical Classification Schemes for Predicting Stroke: Results from the National Registry of Atrial Fibrillation. JAMA ;285(22):  
2. Centers for Medicare & Medicaid Services. Final Decision Memorandum for Percutaneous Left Atrial Appendage Closure (LAAC). memo.aspx?NCAId=281&ExpandComments =n&DocID=CAG N&bc=gAAAAAgAAgAAAA%3d%3d&.
3. Reddy VY, Doshi SK, Sievert H, et al. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-year follow-up of the PROTECT AF (watchman left atrial appendage system for embolic protection in patients with atrial fibrillation) trial. Circulation. 2013; 127:
4. Reddy VY, Doshi SK, Sievert H, et al. Percutaneous Left Atrial Appendage Closure for Stroke Prophylaxis in Patients with Atrial Fibrillation. A Randomized Clinical Trial. JAMA. 2014;312(19): doi: /jama

29. The Effect of CMS Criteria on the Patient Population Selected to Receive the WATCHMAN™ Procedure
Cara Coffelt, PharmD
PGY-1 Pharmacy Resident
St. Joseph’s/Candler Health System
Co-Investigators:
Ashley Woodhouse, PharmD, BCACP, CACP, CDTM
Hannah Brockman, PharmD Candidate