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

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.

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

Adherence to anticoagulation among these high-risk patients is not well described

Rationale

ObjectiveDescribe 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

admission date

sex

discharge date

date of birth

Methods: data sources

Methods: study cohort

Inclusions • Age > 65 years with GWTG-HF hospitalization linked to Medicare claims

8240 patients

• 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

Exclusions • > 90 days of Medicare Part D before index hospitalization (n = 5097)

5549 patients• Contraindications to anticoagulation (n=373)

• Missing documentation (n = 79)

Final population2691 patients

207 sites

Warfarin contraindications

Allerg

y or

com

plica

tion

Bleed

ing

or b

leed

ing

risk

Patie

nt o

r fam

ily re

fusa

l

Serio

us s

ide

effe

ct

Miss

ing

0102030405060

5.6

52.3

6.4 2.1

33.5

%

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

• 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.

Methods:analyzing adherence and persistence

Baseline characteristics

Characteristic Eligible for

Warfarin Therapy(n = 2691)

Did Not Meet theInclusion Criteria

(n = 5549)P Value

Age, median (IQR), y 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

Medical history, No. (%)      

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

Study population by CHADS2 score

1 2 3 4 5 60

10

20

30

40

50

60

3.2

21.9

44.1

19

8.53.3

%

N = 2691

Baseline characteristics

Characteristic Eligible for

Warfarin Therapy(n = 2691)

Did Not Meet theInclusion Criteria

(n = 5549)P Value

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

No. of medications prescribed at discharge, median (IQR)

6.0 (5.0,7.0) 6.0 (5.0, 7.0) < .01

Postdischarge prescription & outpatient dispensing

0

30

60

90

%

N = 2691

Outpatient dispensing, persistence, and adherence

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)

All patients 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)*

Previous non-users        

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)

Existing users        

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)

* 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 analysisPrescription Status Outpatient Dispensing Persistence Adherence

  Filled PrescriptionWithin 90 Days,

No. (Rate)

Filled PrescriptionWithin 1 Year,

No. (Rate)

Discontinued TherapyWithin 1 Year,

No. (Rate)

Medication Possession Ratio,

Median (IQR)All patients 1631 (61.8) 1770 (67.9) 104 (7.1) 0.77 (0.51-0.98)Age group        

65-79 y 847 (64.8)* 926 (71.7)* 54 (7.1) 0.77 (0.52-0.97)≥ 80 y 784 (58.8)* 844 (64.1)* 50 (7.2) 0.77 (0.52-1.00)

Sex        Female 923 (61.6) 994 (67.1) 58 (7.1) 0.78 (0.53-0.99)Male 708 (62.0) 776 (69.0) 46 (7.1) 0.76 (0.49-0.97)

Race        Black 154 (60.3) 162 (63.9) 10 (7.7) 0.79 (0.51-1.03)White 1396 (62.9) 1518 (69.1) 91 (7.2) 0.77 (0.51-0.98)Other/unknown 81 (49.2) 90 (57.0) —** 0.81 (0.57-0.99)

* P < .001 ** To protect patient confidentiality, cells with observations < 11 are not shown.

Prespecified subgroup analysisPrescription Status Outpatient Dispensing Persistence Adherence

 

Filled Prescription

Within 90 Days,No. (Rate)

Filled Prescription

Within 1 Year,No. (Rate)

Discontinued TherapyWithin 1 Year,

No. (Rate)

Medication Possession Ratio,Median (IQR)

All patients 1631 (61.8) 1770 (67.9) 104 (7.1) 0.77 (0.51-0.98)

Coverage gap within 90 days of discharge

       

Yes 545 (61.0) 592 (67.2) 26 (5.3) 0.79 (0.53-1.01)No 1086 (62.2) 1178 (68.2) 78 (8.1) 0.76 (0.50-0.96)

Coverage gap during 1 year of follow-up

       

Yes 902 (63.4) 979 (69.5) 56 (6.7) 0.78 (0.52-1.00)No 729 (59.9) 791 (66.1) 48 (7.8) 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)

All patients 1631 (61.8) 1770 (67.9) 104 (7.1) 0.77 (0.51-0.98)

CHADS2 score        

<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)

Appendix

Sensitivity analysisPrescription 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)

β-Blockers

All patients 937 (82.5) 999 (89.3) 61 (7.2) 0.90 (0.64, 1.03)Prescription at discharge 915 (86.5)* 965 (92.3)* 59 (7.1) 0.92 (0.67, 1.04)*

No prescription at discharge

22 (28.8)* 34 (48.3)* —** 0.58 (0.33, 0.73)*

Angiotensin receptor blockers

All patients 494 (21.1) 573 (25.2) 26 (5.7) 0.76 (0.46, 0.98)

Prescription at discharge 424 (76.3)* 452 (81.9)* 24 (6.2) 0.83 (0.60, 0.99)*

No prescription at discharge

70 (4.0)* 121 (7.5)* —** 0.60 (0.27, 0.81)*

* 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 evidence-based 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