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