Clinical pharmacist led hospital-wide direct oral anticoagulant stewardship program

Amichai Perlman, Ehud Horwitz, Bruria Hirsh-Raccah, Gefen Aldouby-Bier, Tamar Fisher Negev, Sarit Hochberg-Klein, Yosef Kalish, Mordechai Muszkat, Amichai Perlman, Ehud Horwitz, Bruria Hirsh-Raccah, Gefen Aldouby-Bier, Tamar Fisher Negev, Sarit Hochberg-Klein, Yosef Kalish, Mordechai Muszkat

Abstract

Introduction: In the past decade, direct-acting oral anticoagulants (DOAC) have been introduced to medical practice for several indications, with a wide range of dosing regimens. As both over- and under-dosing might lead to life-threatening events, development of methods promoting safe and effective utilization of these agents is imperative. The Hadassah Clinical Pharmacy team initiated a hospital-wide program, for monitoring and promoting safe and effective prescription of DOAC during hospitalization. This study describes the types of drug related problems addressed and the program's performance in terms of consultation rates and physician acceptance.

Methods: Electronic medical records throughout the hospital were screened for DOAC orders. All DOAC orders were assessed by a clinical pharmacist for potentially-inappropriate prescribing. When potentially-inappropriate prescribing or a drug-related problem was identified, the clinical pharmacist provided consultation on management options. In specific cases, additional guidance was provided by coagulation and pharmacology specialists. Data on patient characteristics, clinical pharmacist consultations, and physician response was retrospectively retrieved for the first six months of 2017. Characteristics of patients with and without consultations were compared, consultations were categorized by the recommended management of the drug related problem, and physician acceptance rates were evaluated by category.

Results: During the evaluated period, 585 patients with DOAC orders were identified. Patients were evenly distributed by gender, and age averaged 78 years. Most patients received apixaban (75%) followed by rivaroxaban (14%) and dabigatran (11%), and most (63%) received "reduced dose" regimens. Clinical pharmacists provided 258 consultations for 210 patients, regarding anticoagulation management, such that more than one in three patients on DOAC had potentially inappropriate prescribing or drug related problems. Consultations included alerts regarding potentially inappropriate DOAC doses and recommendations to increase (29%) or decrease (5%) the dose, potentially inappropriate concomitant antiplatelet agents (20%), need for DOAC level monitoring (23%), and alerts regarding other drug related problems (23%). More than 70% of recommendations were accepted by the attending physician.

Conclusion: Due to the complexity of DOAC management, potentially-inappropriate prescribing and drug related problems are common. Multidisciplinary collaborative projects including review and consultation by clinical pharmacists are an effective method of improving management of patients on DOAC.

Trial registration: Retrospectively registered at clinicaltrials.gov, NCT03527615 .

Keywords: Clinical pharmacist; Direct oral anticoagulants; Drug related problems; Drug safety; Potentially inappropriate prescribing.

Conflict of interest statement

Ethics approval and consent to participate

The Hadassah institutional Helsinki committee approved retrospective evaluation and retrieval of data from patient records reviewed in this program and waived informed consent (365–15-HMO).

Consent for publication

Not applicable.

Competing interests

The authors declare they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Figure presents number of recommendations made by clinical pharmacists, and number of recommendations accepted by the attending physician, during the study period according to five categories: recommendations to consider discontinuing concomitant antiplatelet therapy, decrease dose, increase dose, monitoring the plasma level of the anticoagulant (TDM), and “other” recommendations

References

    1. Almutairi AR, Zhou L, Gellad WF, Lee JK, Slack MK, Martin JR, et al. Effectiveness and Safety of Non–vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism: A Systematic Review and Meta-analyses. Clin Ther. 2017;39(7):1456–1478. doi: 10.1016/j.clinthera.2017.05.358.
    1. López-López JA, Sterne JAC, Thom HHZ, Higgins JPT, Hingorani AD, Okoli GN, et al. Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ. 2017;359:j5058. doi: 10.1136/bmj.j5058.
    1. Yu AYX, Malo S, Svenson LW, Wilton SB, Hill MD. Temporal trends in the use and comparative effectiveness of direct Oral anticoagulant agents versus warfarin for Nonvalvular atrial fibrillation: a Canadian population-based study. J Am Heart Assoc. 2017;6(11):e007129. doi: 10.1161/JAHA.117.007129.
    1. Kjerpeseth LJ, Ellekjær H, Selmer R, Ariansen I, Furu K, Skovlund E. Trends in use of warfarin and direct oral anticoagulants in atrial fibrillation in Norway, 2010 to 2015. Eur J Clin Pharmacol. 2017;73(11):1417–1425. doi: 10.1007/s00228-017-2296-1.
    1. Shehab N, Lovegrove MC, Geller AI, Rose KO, Weidle NJ, Budnitz DS. US emergency department visits for outpatient adverse drug events, 2013-2014. JAMA. 2016;316(20):2115. doi: 10.1001/jama.2016.16201.
    1. Nielsen PB, Skjøth F, Søgaard M, Kjældgaard JN, Lip GYH, Larsen TB. Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ. 2017;10:j510. doi: 10.1136/bmj.j510.
    1. Chisholm-Burns MA, Kim Lee J, Spivey CA, Slack M, Herrier RN, Hall-Lipsy E, et al. US Pharmacistsʼ effect as team members on patient care. Med Care. 2010;48(10):923–933. doi: 10.1097/MLR.0b013e3181e57962.
    1. Kaboli PJ, Hoth AB, McClimon BJ, Schnipper JL. Clinical pharmacists and inpatient medical care. Arch Intern Med. 2006;166(9):955. doi: 10.1001/archinte.166.9.955.
    1. Schwartzberg E, Livny S, Sterenberg A, Troitsa A, Oren M, Shani S. Evaluation of the impact of a clinical pharmacist on the quality and cost of pharmacotherapy in a general surgical department, the Hillel-Yaffe medical center. Harefuah. 2003;142(1):5–9.
    1. Hammerman A, Rotem R, Meidan N, Porath A. The clinical pharmacist in internal medicine--impact on the quality of therapeutic care. Harefuah. 1999;136(11):862–864.
    1. Schwartz V, Kravitz MS. A new joint approach to drug management: clinical pharmacy services and risk management unit. Harefuah. 2015;154(4):228–232.
    1. Shekelle PG, Pronovost PJ, Wachter RM, McDonald KM, Schoelles K, Dy SM, et al. The top patient safety strategies that can be encouraged for adoption now. Ann Intern Med. 2013;158(5 Pt 2):365–368. doi: 10.7326/0003-4819-158-5-201303051-00001.
    1. Manzoor BS, Cheng W-H, Lee JC, Uppuluri EM, Nutescu EA. Quality of pharmacist-managed anticoagulation therapy in long-term ambulatory settings: a systematic review. Ann Pharmacother. 2017;51(12):1122–1137. doi: 10.1177/1060028017721241.
    1. Raccah BH, Perlman A, Danenberg HD, Pollak A, Muszkat M, Matok I. Major Bleeding and Hemorrhagic Stroke with Direct Oral Anticoagulants in Patients with Renal Failure Systematic Review and Meta-Analysis of Randomized Trials. Chest. 2016;149(6):1516-24.
    1. Raccah BH, Perlman A, Zwas DR, Hochberg-Klein S, Masarwa R, Muszkat M, et al. Gender differences in efficacy and safety of direct Oral anticoagulants in atrial fibrillation: systematic review and network meta-analysis. Ann Pharmacother. 2018;52(11):1135-42. 10.1177/1060028018771264.
    1. Health M of. Prescribing Information Leaflet - Pradaxa [Internet]. [cited 2018 Sep 18]. Available from:
    1. Health M of. Prescribing Information Leaflet - Xarelto [Internet]. [cited 2018 Sep 18]. Available from:
    1. Health M of. Prescribing Information Leaflet - Eliquis [Internet]. [cited 2018 Sep 18]. Available from:
    1. Heidbuchel H, Verhamme P, Alings M, Antz M, Diener H-C, Hacke W, et al. Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: Executive summary. Eur Heart J. 2016;38(27):ehw058. doi: 10.1093/eurheartj/ehw058.
    1. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace. 2016;18(11):1609–1678. doi: 10.1093/europace/euw295.
    1. Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, et al. The 2018 European heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: executive summary. EP Europace 2018;20(8):1231–42. 10.1093/europace/euy054.
    1. R Core Team. R Core Team (2017). R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. .
    1. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279(15):1200–1205. doi: 10.1001/jama.279.15.1200.
    1. van der Sijs H, Aarts J, Vulto A, Berg M. Overriding of drug safety alerts in computerized physician order entry. J Am Med Informatics Assoc. 2006;13(2):138–147. doi: 10.1197/jamia.M1809.
    1. Zenziper Straichman Y, Kurnik D, Matok I, Halkin H, Markovits N, Ziv A, et al. Prescriber response to computerized drug alerts for electronic prescriptions among hospitalized patients. Int J Med Inform. 2017;107:70–75. doi: 10.1016/j.ijmedinf.2017.08.008.
    1. Somers A, Robays H, De Paepe P, Van Maele G, Perehudoff K, Petrovic M. Evaluation of clinical pharmacist recommendations in the geriatric ward of a Belgian university hospital. Clin Interv Aging. 2013;8:703–709. doi: 10.2147/CIA.S42162.
    1. Selcuk A, Sancar M, Okuyan B, Demirtunc R, Izzettin FV. The potential role of clinical pharmacists in elderly patients during hospital admission. Pharmazie. 2015;70(8):559–562.
    1. Saokaew S, Sapoo U, Nathisuwan S, Chaiyakunapruk N, Permsuwan U. Anticoagulation control of pharmacist-managed collaborative care versus usual care in Thailand. Int J Clin Pharm. 2012;34(1):105–112. doi: 10.1007/s11096-011-9597-8.
    1. Steinberg BA, Shrader P, Pieper K, Thomas L, Allen LA, Ansell J, et al. Frequency and outcomes of reduced dose non–vitamin K antagonist anticoagulants: results from ORBIT-AF II (the outcomes registry for better informed treatment of atrial fibrillation II) J Am Heart Assoc. 2018;7(4):e007633. doi: 10.1161/JAHA.117.007633.
    1. Yao X, Shah ND, Sangaralingham LR, Gersh BJ, Noseworthy PA. Non–vitamin K antagonist Oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. J Am Coll Cardiol. 2017;69(23):2779–2790. doi: 10.1016/j.jacc.2017.03.600.
    1. Carlin S, Pickering J, Schulman S. Appropriateness of Apixaban dosing to prevent stroke in patients with atrial fibrillation: a pilot study. Can J Hosp Pharm. 2016;69(6):449–453.
    1. Nguyen E, White CM, Patel MR, Fields LE, Peacock WF, Crivera C, et al. Doses of apixaban and rivaroxaban prescribed in real-world United States cardiology practices compared to registration trials. Curr Med Res Opin. 2016;32(7):1277–1279. doi: 10.1185/03007995.2016.1170672.
    1. Steinberg BA, Kim S, Piccini JP, Fonarow GC, Lopes RD, Thomas L, et al. Use and associated risks of concomitant aspirin therapy with Oral anticoagulation in patients with atrial fibrillation: insights from the outcomes registry for better informed treatment of atrial fibrillation (ORBIT-AF) registry. Circulation. 2013;128(7):721–728. doi: 10.1161/CIRCULATIONAHA.113.002927.
    1. Shah R, Hellkamp A, Lokhnygina Y, Becker RC, Berkowitz SD, Breithardt G, et al. Use of concomitant aspirin in patients with atrial fibrillation: findings from the ROCKET AF trial. Am Heart J. 2016;179:77–86. doi: 10.1016/j.ahj.2016.05.019.
    1. Hylek EM, Held C, Alexander JH, Lopes RD, De Caterina R, Wojdyla DM, et al. Major bleeding in patients with atrial fibrillation receiving Apixaban or warfarin. J Am Coll Cardiol. 2014;63(20):2141–2147. doi: 10.1016/j.jacc.2014.02.549.
    1. Favaloro EJ, Pasalic L, Curnow J, Lippi G. Laboratory monitoring or measurement of direct Oral anticoagulants (DOACs): advantages, limitations and future challenges. Curr Drug Metab. 2017;18(7):598–608. doi: 10.2174/1389200218666170417124035.
    1. Lock J, Patel RK, Brookes C, Patel JP. Clinical experience of prescribing dabigatran Etexilate with Dronedarone. Ther Drug Monit. 2016;38(6):813–814. doi: 10.1097/FTD.0000000000000328.
    1. Douxfils J, Ageno W, Samama C-M, Lessire S, ten Cate H, Verhamme P, et al. Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians. J Thromb Haemost. 2018;16(2):209–219. doi: 10.1111/jth.13912.
    1. Breuer L, Ringwald J, Schwab S, Köhrmann M. Ischemic Stroke in an Obese Patient Receiving Dabigatran. N Engl J Med. 2013;368(25):2440–2442. doi: 10.1056/NEJMc1215900.
    1. De Caterina R, Lip GYH. The non-vitamin K antagonist oral anticoagulants (NOACs) and extremes of body weight—a systematic literature review. Clin Res Cardiol. 2017;106(8):565–572. doi: 10.1007/s00392-017-1102-5.
    1. Rottenstreich A, Barkai A, Arad A, Raccah BH, Kalish Y. The effect of bariatric surgery on direct-acting oral anticoagulant drug levels. Thromb Res. 2017.
    1. American Society of Hospital Pharmacists. ASHP guidelines: minimum standard for pharmacies in hospitals. Am J Health-Syst Pharm. 2013;70:1619–30.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する