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 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

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 population 2691 patients 207 sites

Warfarin contraindications

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 the Inclusion Criteria (n = 5549) P Value Age, median (IQR), y80.0 ( )80.0 ( )<.01 Male, No. (%)1168 (43.4)3137 (56.5)<.01 White race, No. (%)2261 (84.0)4979 (89.7)<.01 Medical history, No. (%) Anemia463 (17.2)973 (17.5).71 Cerebrovascular accident or TIA440 (16.4)886 (16.0).66 Diabetes mellitus1002 (37.2)1877 (33.8)<.01 Heart failure with ischemic etiology1654 (61.5)3546 (63.9).03 Hypertension2073 (77.0)4111 (74.1)<.01 Renal insufficiency435 (16.2)992 (17.9).05

Study population by CHADS 2 score N = 2691

Baseline characteristics Characteristic Eligible for Warfarin Therapy (n = 2691) Did Not Meet the Inclusion Criteria (n = 5549) P Value Medications at discharge, No. (%) ACE inhibitor and/or ARB1722 (64.0)3459 (62.3).15 Aldosterone antagonist426 (15.8)908 (16.4).54 Antiplatelet agents1354 (50.3)2747 (49.5).49 Aspirin1333 (49.5)2714 (48.9).59 Clopidogrel373 (13.9)747 (13.5).62 Aspirin plus clopidogrel252 (9.4)513 (9.2).86 β-Blocker2100 (78.0)4286 (77.2).42 Digoxin848 (31.5)1687 (30.4).31 Lipid-lowering agent1432 (53.2)2906 (52.4).47 Diuretic2129 (79.1)4334 (78.1).30 No. of medications prescribed at discharge, median (IQR)6.0 (5.0,7.0) <.01

Postdischarge prescription & outpatient dispensing N = 2691

Outpatient dispensing, persistence, and adherence Prescription StatusOutpatient DispensingPersistenceAdherence 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 patients1631 (61.8)1770 (67.9)104 (7.1)0.77 ( ) Prescription at discharge1530 (84.5) * 1637 (91.6) * 98 (7.2)0.78 ( ) * No prescription at discharge101 (12.3) * 133 (16.8) * — ** 0.63 ( ) * Previous non-users Prescription at discharge162 (86.1) * 169 (91.6) * 19 (12.6)0.74 ( ) No prescription at discharge34 (4.9) * 58 (9.0) * — ** 0.54 ( ) Existing users Prescription at discharge1368 (84.2) * 1468 (91.5) * 79 (6.5)0.78 ( ) No prescription at discharge67 (51.1) * 75 (58.1) * — ** 0.74 ( ) * 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 StatusOutpatient DispensingPersistenceAdherence 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 patients1631 (61.8)1770 (67.9)104 (7.1)0.77 ( ) Age group y847 (64.8) * 926 (71.7) * 54 (7.1)0.77 ( ) ≥ 80 y784 (58.8) * 844 (64.1) * 50 (7.2)0.77 ( ) Sex Female923 (61.6)994 (67.1)58 (7.1)0.78 ( ) Male708 (62.0)776 (69.0)46 (7.1)0.76 ( ) Race Black154 (60.3)162 (63.9)10 (7.7)0.79 ( ) White1396 (62.9)1518 (69.1)91 (7.2)0.77 ( ) Other/unknown81 (49.2)90 (57.0)— ** 0.81 ( ) * P <.001 ** To protect patient confidentiality, cells with observations < 11 are not shown.

Prespecified subgroup analysis Prescription StatusOutpatient DispensingPersistenceAdherence 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 patients1631 (61.8)1770 (67.9)104 (7.1)0.77 ( ) Coverage gap within 90 days of discharge Yes545 (61.0)592 (67.2)26 (5.3)0.79 ( ) No1086 (62.2)1178 (68.2)78 (8.1)0.76 ( ) Coverage gap during 1 year of follow-up Yes902 (63.4)979 (69.5)56 (6.7)0.78 ( ) No729 (59.9)791 (66.1)48 (7.8)0.75 ( )

Outpatient dispensing, adherence, and persistence by CHADS 2 score Prescription Status Outpatient DispensingPersistenceAdherence 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 patients1631 (61.8)1770 (67.9)104 (7.1)0.77 ( ) CHADS 2 score <3422 (63.6)459 (70.1)31 (8.1)0.76 ( ) ≥31209 (61.2)1311 (67.2)73 (6.8)0.77 ( ) Appendix

Sensitivity analysis Prescription StatusOutpatient DispensingPersistenceAdherence 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 patients937 (82.5)999 (89.3)61 (7.2)0.90 (0.64, 1.03) Prescription at discharge915 (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 patients494 (21.1)573 (25.2)26 (5.7)0.76 (0.46, 0.98) Prescription at discharge424 (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 ( N). The study was also funded under contract #HHSA I (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.

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