Adherence and Persistence in the Use of
Warfarin After Hospital Discharge
Among Patients With Heart Failure and
Atrial Fibrillation
Zubin J. Eapen, Xiaojuan Mi, Laura G. Qualls, Bradley G. Hammill, Gregg C.
Fonarow, Mintu P. Turakhia, Paul A. Heidenreich, Eric D. Peterson, Lesley H.
Curtis, Adrian F. Hernandez, Sana M. Al-Khatib
AHA Scientific Sessions
November 7, 2012
Presenter disclosure information
ZJ Eapen: none
X Mi: none
LG Qualls: none
BG Hammill: none
GC Fonarow: consultant for Amgen, Gambro, GlaxoSmithKline, Medtronic, Merck, Novartis, Pfizer, Relypsa,
Scios, St. Jude, Takeda, and the Medicines Company; employment with the Ahmanson Foundation; service
as the Eliot Corday Chair of Cardiovascular Medicine and Science; grants from the Agency for Healthcare
Research and Quality, the National Institutes of Health, and GlaxoSmithKline; speakers fees from Boston
Scientific/Guidant, GlaxoSmithKline, Medtronic, Merck, Novartis, Pfizer, and St. Jude Medical.
MP Turakhia: consultant for Medtronic, Precision Health Economics, and St. Jude Medical; grants from the
American Heart Association, Gilead Sciences, iRhythm, and Medtronic; speakers fees from Boston
Scientific and St. Jude Medical; stock in Zipline Medical; travel/meeting expenses from Medtronic.
PA Heidenreich: none
ED Peterson: grants from Eli Lilly and Janssen Pharmaceuticals.
LH Curtis: grants from GlaxoSmithKline and Johnson & Johnson.
AF Hernandez: grant from Portola Pharmaceuticals.
SM Al-Khatib: travel/meeting expenses from Bristol-Myers Squibb.
DISCLOSURE INFORMATION:
Background
• Practice guidelines recommend warfarin at hospital
discharge for patients with heart failure (HF) and atrial
fibrillation (AF)
• Warfarin prescription at hospital discharge is an
ACC/AHA clinical performance measure for patients
with HF and AF
• More than one-third of eligible patients with HF and AF
are not discharged with a prescription for warfarin
Rationale
Adherence to anticoagulation among these high-risk
patients is not well described
Objective
Describe the transitional and long-term adherence to
anticoagulation therapy among Medicare beneficiaries with
HF and AF
Methods: data sources
• Demographics
• Medical history
• Results of laboratory tests and
examinations
• Discharge medications
• Medicare Part A
• hospitalization claims
• Denominator files
• program eligibility and
enrollment
• date of death
• Medicare Part D
• generic names of prescription
drugs
• days’ supply
• program enrollment and benefit
phases
Methods: data sources
admission date
discharge date
sex
date of birth
Methods: study cohort
Inclusions
Exclusions
Final population
•
Age > 65 years with GWTG-HF hospitalization
linked to Medicare claims
•
Discharged home between January 1, 2006
and December 31, 2009
•
Enrolled in fee-for-service Medicare at
discharge
•
AF in medical history and recorded admission
vital signs
•
> 90 days of Medicare Part D before index
hospitalization (n = 5097)
•
Contraindications to anticoagulation (n=373)
•
Missing documentation (n = 79)
8240 patients
5549 patients
2691 patients
207 sites
Warfarin contraindications
60
52.3
40
33.5
%
20
6.4
5.6
2.1
0
Allergy or
complication
Bleeding or
bleeding risk
Patient or family
refusal
Serious side
effect
Missing
Methods:
measuring adherence and persistence
• Obtained postdischarge prescription claims for
warfarin from Medicare Part D claims during 1 year
after discharge from the index hospitalization
• Defined the initial outpatient dispensing date as the
date of the first prescription claim during 1 year of
follow-up
• Calculated the days to the first outpatient prescription
claim from the index discharge date
Methods:
analyzing adherence and persistence
• Outpatient dispensing rates: cumulative incidence of
the first filled outpatient prescription for warfarin within
90 days or 1 year after discharge from the index
hospitalization.
• Discontinuation of therapy: first 90-day gap in the
days’ supply of warfarin during 1 year of follow-up.
• Medication possession ratio: sum of the days’ supply
of warfarin divided by the number of days alive during
1 year of follow-up.
Baseline characteristics
Eligible for
Warfarin Therapy
(n = 2691)
Did Not Meet the
Inclusion Criteria
(n = 5549)
P Value
80.0 (73.0-85.0)
80.0 (75.0-85.0)
< .01
Male, No. (%)
1168 (43.4)
3137 (56.5)
< .01
White race, No. (%)
2261 (84.0)
4979 (89.7)
< .01
Anemia
463 (17.2)
973 (17.5)
.71
Cerebrovascular accident or TIA
440 (16.4)
886 (16.0)
.66
Diabetes mellitus
1002 (37.2)
1877 (33.8)
< .01
Heart failure with ischemic etiology
1654 (61.5)
3546 (63.9)
.03
Hypertension
2073 (77.0)
4111 (74.1)
< .01
Renal insufficiency
435 (16.2)
992 (17.9)
.05
Characteristic
Age, median (IQR), y
Medical history, No. (%)
Study population by CHADS2 score
60
44.1
40
%
21.9
19.0
20
8.5
3.3
3.2
0
1
2
3
4
5
6
N = 2691
Baseline characteristics
Characteristic
Eligible for
Did Not Meet the
Warfarin Therapy Inclusion Criteria P Value
(n = 2691)
(n = 5549)
Medications at discharge, No. (%)
ACE inhibitor and/or ARB
1722 (64.0)
3459 (62.3)
.15
Aldosterone antagonist
426 (15.8)
908 (16.4)
.54
Antiplatelet agents
1354 (50.3)
2747 (49.5)
.49
Aspirin
1333 (49.5)
2714 (48.9)
.59
Clopidogrel
373 (13.9)
747 (13.5)
.62
Aspirin plus clopidogrel
252 (9.4)
513 (9.2)
.86
β-Blocker
2100 (78.0)
4286 (77.2)
.42
Digoxin
848 (31.5)
1687 (30.4)
.31
Lipid-lowering agent
1432 (53.2)
2906 (52.4)
.47
Diuretic
2129 (79.1)
4334 (78.1)
.30
6.0 (5.0,7.0)
6.0 (5.0, 7.0)
< .01
No. of medications prescribed at discharge, median (IQR)
Postdischarge prescription &
outpatient dispensing
100
80
69
61.8
67.9
60
%
40
20
0
Prescribed warfarin Filled prescription
at discharge
within 90 days
Filled prescription
within 1 year
N = 2691
Outpatient dispensing, persistence, and adherence
Prescription Status
Outpatient Dispensing
Filled
Prescription
Within 90
Days,
No. (Rate)
All patients
Filled
Prescription
Within 1 Year,
No. (Rate)
Persistence
Adherence
Discontinued
Therapy
Within 1 Year,
No. (Rate)
Medication
Possession Ratio,
Median (IQR)
1631 (61.8)
1770 (67.9)
104 (7.1)
0.77 (0.51-0.98)
Prescription at discharge
1530 (84.5)*
1637 (91.6)*
98 (7.2)
0.78 (0.52-0.99)*
No prescription at discharge
101 (12.3)*
133 (16.8)*
—**
0.63 (0.35-0.88)*
Prescription at discharge
162 (86.1)*
169 (91.6)*
19 (12.6)
0.74 (0.38-0.96)
No prescription at discharge
34 (4.9)*
58 (9.0)*
—**
0.54 (0.31-0.82)
Prescription at discharge
1368 (84.2)*
1468 (91.5)*
79 (6.5)
0.78 (0.54-0.99)
No prescription at discharge
67 (51.1)*
75 (58.1)*
—**
0.74 (0.43-0.93)
Previous non-users
Existing users
* P < .001 for the comparison between patients prescribed warfarin at discharge and patients not prescribed warfarin at discharge.
** To protect patient confidentiality, cells with observations < 11 are not shown.
Prespecified subgroup analysis
Prescription Status
All patients
Age group
65-79 y
≥ 80 y
Sex
Female
Male
Race
Black
White
Other/unknown
Outpatient Dispensing
Persistence
Adherence
Filled Prescription Filled Prescription
Within 90 Days,
Within 1 Year,
No. (Rate)
No. (Rate)
1631 (61.8)
1770 (67.9)
Discontinued Therapy
Within 1 Year,
No. (Rate)
104 (7.1)
Medication
Possession Ratio,
Median (IQR)
0.77 (0.51-0.98)
847 (64.8)*
784 (58.8)*
926 (71.7)*
844 (64.1)*
54 (7.1)
50 (7.2)
0.77 (0.52-0.97)
0.77 (0.52-1.00)
923 (61.6)
708 (62.0)
994 (67.1)
776 (69.0)
58 (7.1)
46 (7.1)
0.78 (0.53-0.99)
0.76 (0.49-0.97)
154 (60.3)
1396 (62.9)
81 (49.2)
162 (63.9)
1518 (69.1)
90 (57.0)
10 (7.7)
91 (7.2)
—**
0.79 (0.51-1.03)
0.77 (0.51-0.98)
0.81 (0.57-0.99)
* P < .001
** To protect patient confidentiality, cells with observations < 11 are not shown.
Prespecified subgroup analysis
Prescription Status
All patients
Coverage gap within
90 days of
discharge
Yes
No
Coverage gap
during 1 year of
follow-up
Yes
No
Outpatient Dispensing
Persistence
Adherence
Discontinued Therapy
Within 1 Year,
No. (Rate)
Medication Possession Ratio,
Median (IQR)
104 (7.1)
0.77 (0.51-0.98)
Filled
Prescription
Within 90 Days,
No. (Rate)
1631 (61.8)
Filled
Prescription
Within 1 Year,
No. (Rate)
1770 (67.9)
545 (61.0)
1086 (62.2)
592 (67.2)
1178 (68.2)
26 (5.3)
78 (8.1)
0.79 (0.53-1.01)
0.76 (0.50-0.96)
902 (63.4)
729 (59.9)
979 (69.5)
791 (66.1)
56 (6.7)
48 (7.8)
0.78 (0.52-1.00)
0.75 (0.50-0.96)
Outpatient dispensing, adherence,
and persistence by CHADS2 score
Prescription
Status
Outpatient Dispensing
Persistence
Adherence
Filled
Prescription
Within 90 Days,
No. (Rate)
Filled
Prescription
Within 1 Year,
No. (Rate)
Discontinued
Therapy
Within 1 Year,
No. (Rate)
Medication Possession
Ratio,
Median (IQR)
1631 (61.8)
1770 (67.9)
104 (7.1)
0.77 (0.51-0.98)
<3
422 (63.6)
459 (70.1)
31 (8.1)
0.76 (0.49-0.96)
≥3
1209 (61.2)
1311 (67.2)
73 (6.8)
0.77 (0.52-0.99)
All patients
CHADS2 score
Appendix
Sensitivity analysis
Prescription Status
Outpatient Dispensing
Persistence
Adherence
Discontinued
Therapy
Within 1 Year,
No. (Rate)
Medication Possession Ratio,
Median (IQR)
Filled
Prescription
Within 90 Days,
No. (Rate)
Filled
Prescription
Within 1 Year,
No. (Rate)
937 (82.5)
915 (86.5)*
999 (89.3)
965 (92.3)*
61 (7.2)
59 (7.1)
0.90 (0.64, 1.03)
0.92 (0.67, 1.04)*
22 (28.8)*
34 (48.3)*
—**
0.58 (0.33, 0.73)*
494 (21.1)
573 (25.2)
26 (5.7)
0.76 (0.46, 0.98)
424 (76.3)*
452 (81.9)*
24 (6.2)
0.83 (0.60, 0.99)*
70 (4.0)*
121 (7.5)*
—**
0.60 (0.27, 0.81)*
β-Blockers
All patients
Prescription at discharge
No prescription at
discharge
Angiotensin receptor blockers
All patients
Prescription at discharge
No prescription at
discharge
* P < .001 for the comparison between patients prescribed therapy at discharge and patients not prescribed therapy at discharge.
** To protect patient confidentiality, cells with observations < 11 are not shown.
Limitations
• We restricted the analysis to fee-for-service
Medicare beneficiaries 65 years or older
enrolled in Medicare Part D.
• A proportion of the failure to prescribe may be
due to undocumented physician impressions
• Adherence was assessed by outpatient
dispensing rather than actual monitoring
Conclusions
• One-third of eligible patients with HF and AF were not
prescribed warfarin therapy at discharge from a HF
hospitalization.
• Eligible patients without a discharge prescription seldom
initiated therapy as outpatients.
• In contrast, the majority of patients who were prescribed
warfarin at discharge filled the prescription within 90
days and remained on therapy for 1 year.
• These findings highlight the importance of hospital
discharge and care transitions for enhancing evidencebased prescribing of anticoagulation therapy.
Acknowledgements
• This study was supported by an award from the American Heart
Association Pharmaceutical Roundtable and David and Stevie
Spina.
• Dr Eapen received funding from an American Heart Association
Pharmaceutical Roundtable outcomes training grant
(0875142N).
• The study was also funded under contract
#HHSA29020050032I (Duke University DEcIDE Center) from
the Agency for Healthcare Research and Quality, US
Department of Health and Human Services, as part of the
Developing Evidence to Inform Decisions About Effectiveness
(DEcIDE) program.
Thank you