The effectiveness of Pharmacist-driven Medication optimization: A Retrospective study on Warfarin and Digoxin
Main Article Content
Keywords
Warfarin, Digoxin, Clinical Pharmacists, Polypharmacy, Chronic Kidney Disease, Medication Adherence, Therapeutic Drug Monitoring, Hospital Readmissions
Abstract
Background: Warfarin and digoxin are essential for managing cardiovascular conditions but carry risks of adverse drug reactions (ADRs) due to their narrow therapeutic indices, particularly in patients on concurrent therapy, with polypharmacy, or chronic kidney disease (CKD). The role of clinical pharmacists in optimizing these therapies remains underexplored. Objective: To evaluate the impact of pharmacist-driven interventions on therapeutic success, ADRs, medication adherence, and hospital readmissions in patients on warfarin, digoxin, or both. Methods: This retrospective cohort study analyzed 270 patients at Farah Medical Complex, Amman, Jordan, from January to December 2023. Outcomes included therapeutic success, time to therapeutic target and stabilization, ADR incidence, adherence, and hospital readmissions. Data were analyzed using Kaplan-Meier survival analysis, Cox proportional hazards models, and multivariate logistic regression. Results: Of 270 patients (162 warfarin-only, 80 digoxin-only, 28 concurrent), pharmacists delivered 277 interventions (1.03/patient), achieving therapeutic success in 83.7% (226/270). Warfarin-only patients reached therapeutic INR in 88.2% within 8.2 ± 11 days, digoxin-only in 86.3% within 11 ± 13 days, and concurrent therapy in 85.7% (INR) and 71.4% (digoxin) within 9.1 ± 9 and 14 ± 11 days, stabilizing at 26–33 days. Frequent interventions (HR=1.61–1.92, p<0.001–0.014) reduced stabilization time by 7–12 days. Interventions tripled success odds (OR=2.87, p<0.001), prevented 18 ADRs (reducing the rate from 20.4% to 13.7%), and improved adherence odds (OR=1.73, p=0.07), increasing PDC by 6–12%. Polypharmacy (OR=1.89, p=0.02), CKD (OR=3.21, p=0.003), and concurrent therapy (OR=2.13, p=0.04) increased ADR risk, while polypharmacy reduced adherence (OR=0.58, p=0.02). Readmissions (38 events, 14.1% event rate) were reduced from 17.0% by preventing 8 events, though the concurrent subgroup had a 35.7% rate. Conclusions: Pharmacist-driven interventions significantly enhance therapeutic success, reduce ADRs, improve adherence, and lower readmissions in warfarin and digoxin therapy, particularly in high-risk patients, supporting their integration into cardiovascular care teams.
References
2. Gheorghiade M, Fonarow GC. Management of digoxin toxicity in the modern era. Circulation. 2013;127(4):469-478. Available from: https://doi.org/10.1161/CIRCULATIONAHA.112.000679
3. Kanji S, MacLean RD. Cardiac glycoside toxicity: more than 200 years and counting. Crit Care Clin. 2012;28(4):527-535. Available from: https://doi.org/10.1016/j.ccc.2012.07.002
4. Ahmed A, Waagstein F, Pitt B, White M, Love TE, Aban IB, et al. Effectiveness of digoxin in reducing one-year mortality in chronic heart failure in the Digitalis Investigation Group trial. Eur Heart J. 2009;30(14):1781-1787. Available from: https://doi.org/10.1093/eurheartj/ehp206
5. Adams KF Jr, Patterson JH, Gattis WA, O’Connor CM, Lee CR, Schwartz TA, et al. Relationship of serum digoxin concentration to mortality and morbidity in women in the Digitalis Investigation Group trial: a retrospective analysis. J Am Coll Cardiol. 2005;46(3):497-504. Available from: https://doi.org/10.1016/j.jacc.2005.03.075
6. Hauptman PJ, Kelly RA. Digitalis. Circulation. 1999;99(9):1265-1270. Available from: https://doi.org/10.1161/01.CIR.99.9.1265
7. Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA. 2003;289(7):871-878. Available from: https://doi.org/10.1001/jama.289.7.871
8. Weber C, Meyer-Massetti C, Schönenberger N. Pharmacist-led interventions at hospital discharge: a scoping review of studies demonstrating reduced readmission rates. Int J Clin Pharm. 2025 Feb;47(1):15-30. https://doi.org/10.1007/s11096-024-01821-y
9. Rattanavipanon W, Chaiyasothi T, Puchsaka P, Mungkornkaew R, Nathisuwan S, Veettil SK, et al. Effects of pharmacist interventions on cardiovascular risk factors and outcomes: an umbrella review of meta-analysis of randomized controlled trials. Br J Clin Pharmacol. 2022 Jul 1;88(7):3064-77. Available from: https://doi.org/10.1111/bcp.15279
10. Alghadeeer S, Alzahrani AA, Alalayet WY, Alkharashi AA, Alarifi MN. Anticoagulation control of warfarin in pharmacist-led clinics versus physician-led clinics: a prospective observational study. Risk Manag Healthc Policy. 2020;13:1175-9. https://doi.org/10.2147/RMHP.S248222
11. Alshaiban A, Alavudeen SS, Alshahrani I, Kardam AM, Alhasan IM, Alasiri SA, et al. Impact of clinical pharmacist running anticoagulation clinic in Saudi Arabia. J Clin Med. 2023;12(12):3887. https://doi.org/10.3390/jcm12123887
12. Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011;123(21):2363-72. https://doi.org/10.1161/CIRCULATIONAHA.110.004747
13. Andrews P, Anseeuw K, Kotecha D, Lapostolle F, Thanacoody R. Diagnosis and practical management of digoxin toxicity: a narrative review and consensus. Eur J Emerg Med. 2023 Dec;30(6):395-401. https://doi.org/10.1097/MEJ.0000000000001065
14. Marcum ZA, Jiang S, Bacci JL, Ruppar TM. Pharmacist-led interventions to improve medication adherence in older adults: a meta-analysis. Am J Geriatr Pharmacother. 2013;11(5):378-388.
