Old age, high risk medication, polypharmacy: a trilogy of risks in older patients with atrial fibrillation

Keywords: Polypharmacy, Atrial Fibrillation, Drug-Related Side Effects and Adverse Reactions, Aged, Inappropriate Prescribing, Australia


Background: The safety of pharmacotherapy in atrial fibrillation (AF) is compounded by a trilogy of risks old age, high-risk medications (e.g., antithrombotics, antiarrhythmics), polypharmacy due to multiple patient comorbidities. However, to date, scarce study has investigated the use of polypharmacy (including potentially inappropriate medication (PIM)) in AF patients, and how this may contribute to their overall risk of medication misadventure.

Objectives: To review the extent of polypharmacy and PIM use in older patients (65 years or older) with AF.

Methods: Information was extracted from a database characterising a cohort of older AF patients treated in general practice in New South Wales, Australia. Patient characteristics, number and types of drugs, the degree of PIM use were recorded. The predictors for the use of polypharmacy in older AF patients were identified.

Results: Overall, 367 patients (mean age 77.8 years) were reviewed, among which 94.8% used 5 medications or more and over half used 10 medications or more. Cardiovascular agents were most commonly used (98.9%), followed by antithrombotics (90.7%). Among agents deemed PIMs, digoxin (30.2%) was the most frequently used, followed by benzodiazepines (19.6%), and sotalol (9.8%). AF patients using polypharmacy were more likely to have low bleeding risk (OR=10.97), representing those patients in whom high-risk antithrombotics are mostly indicated. Patients with major-polypharmacy (5-9 medications) are more likely to have obstructive pulmonary diseases (OR=2.32), upper gastrointestinal diseases (OR=2.02) and poor physical function (OR=1.04), but less likely to have cognitive impairment (OR=0.27).

Conclusion: Polypharmacy affects oldest AF patients, comprising medications that are indicated for AF, yet regarded as PIMs. Patients with lower risk of bleeding, obstructive pulmonary diseases, upper gastrointestinal diseases and poor physical function are also at higher risk of using higher number of medications. This may lead to an increased risk for medication misadventure due to the concomitant use of polypharmacy and medications for AF.


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Author Biographies

Yishen Wang

Student Doctor of Philosophy

UTS Pharmacy

Shamsher Singh

Student Doctor of Philosophy

UTS Pharmacy

Beata Bajorek
Associate Professor


1. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1-e76. doi: 10.1016/j.jacc.2014.03.022

2. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P; ESC Committee for Practice Guidelines-CPG; Document Reviewers. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation--developed with the special contribution of the European Heart Rhythm Association. Europace. 2012;14(10):1385-1413.

3. Skov J, Bladbjerg EM, Sidelmann J, Vamosi M, Jespersen J. Plenty of pills: polypharmacy prevails in patients of a Danish anticoagulant clinic. Eur J Clin Pharmacol. 2011;67(11):1169-1174. doi: 10.1007/s00228-011-1045-0

4. Bajorek B. A review of the safety of anticoagulants in older people using the medicines management pathway: weighing the benefits against the risks. Ther Adv Drug Saf. 2011;2(2):45-58. doi: 10.1177/2042098611400495

5. Hajjar ER, Cafiero AC, Hanlon JT. Polypharmacy in elderly patients. Am J Geriatr Pharmacother. 2007 ec;5(4):345-351. doi: 10.1016/j.amjopharm.2007.12.002

6. Capodanno D, Angiolillo DJ. Antithrombotic therapy in the elderly. J Am Coll Cardiol. 2010;56(21):1683-1692. doi: 10.1016/j.jacc.2010.04.063

7. Joppi R, Cinconze E, Mezzalira L, Pase D, Poggiani C, Rossi E, Pengo V; Italian Horizon Scanning Project. Hospitalized patients with atrial fibrillation compared to those included in recent trials on novel oral anticoagulants: a population-based study. Eur J Intern Med. 2013 Jun;24(4):318-23. doi: 10.1016/j.ejim.2013.02.018

8. LaMori JC, Mody SH, Gross HJ, daCosta DiBonaventura M, Patel AA, Schein JR, Nelson WW. Burden of comorbidities among patients with atrial fibrillation. Ther Adv Cardiovasc Dis. 2013;7(2):53-62. doi: 10.1177/1753944712464101

9. Bajorek B, Magin P, Hilmer S, Krass I. A cluster-randomized controlled trial of a computerized antithrombotic risk assessment tool to optimize stroke prevention in general practice: a study protocol. BMC Health Serv Res. 2014;14:55. doi: 10.1186/1472-6963-14-55

10. Hubbard RE, Peel NM, Scott IA, Martin JH, Smith A, Pillans PI, Poudel A, Gray LC. Polypharmacy among inpatients aged 70 years or older in Australia. Med J Aust. 2015;202(7):373-377.

11. Koh Y, Kutty FBM, Li SC. Drug-related problems in hospitalized patients on polypharmacy: the influence of age and gender. Ther Clin Risk Manag. 2005;1(1):39-48.

12. World Health Organization. International Statistical Classification of Diseases and Related Health Problems 10th Revision. http://appswhoint/classifications/icd10/browse/2010/en (accessed Dec 08 2013).

13. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285(22):2864-2870.

14. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137(2):263-272. doi: 10.1378/chest.09-1584

15. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-1100. doi: 10.1378/chest.10-0134

16. Gage BF, Yan Y, Milligan PE, Waterman AD, Culverhouse R, Rich MW, Radford MJ.Clinical classification schemes for predicting hemorrhage: Results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J. 2006;151(3):713-719.

17. NPS MEDICINEWISE. Good anticoagulant practice. http://wwwnpsorgau/publications/health-professional/medicinewise-news/2013/good-anticoagulant-practice (accessed June 16, 2015).

18. eTG complete [online]. Therapeutic Guidelines: Cardiovascular. Version 6. Melbourne: Therapeutic Guidelines Limited. 2012.

19. National Clinical Guideline C. National Institute for Health and Clinical Excellence: Guidance. Atrial Fibrillation: The Management of Atrial Fibrillation. London: National Institute for Health and Care Excellence (UK) Copyright (c) National Clinical Guideline Centre, 2014.; 2014.

20. John E. Ware. SF-36® Health Survey Update 2014. http://wwwsf-36org/tools/sf36shtml (accessed February 2, 2015).

21. WHO Collaborating Center for Drug Statistics Methodology. Anatomical Therapeutic Chemical (ATC) classification system http://wwwwhoccno/atc_ddd_index/ (accessed June 16, 2015).

22. The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. http://wwwamericangeriatricsorg/files/documents/beers/2012BeersCriteria_JAGSpdf (accessed Nov 14, 2013).

23. Holt S, Schmiedl S, Thurmann PA. Potentially inappropriate medications in the elderly: the PRISCUS list. Dtsch Arztebl Int. 2010;107(31-32):543-551. doi: 10.3238/arztebl.2010.0543

24. Cardiovascular Expert Group. Therapeutic guidelines: cardiovascular. Version 6. Melbourne: Therapeutic Guidelines Limited; 2012.
25. Junius-Walker U, Theile G, Hummers-Pradier E. Prevalence and predictors of polypharmacy among older primary care patients in Germany. Fam Pract. 2007;24(1):14-19.

26. Carvalho MF, Romano-Lieber NS, Bergsten-Mendes G, Secoli SR, Ribeiro E, Lebrão ML, Duarte YA. Polypharmacy among the elderly in the city of Sao Paulo, Brazil - SABE Study. Rev Bras Epidemiol. 2012;15(4):817-827.

27. Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365(21):2002-2012. doi: 10.1056/NEJMsa1103053

28. Yip A, Bajorek BV. Identifying temporal changes to the prescribing of anti-arrhythmics for atrial fibrillation. J Pharm Pract Res. 2010;40(4).

29. McAlister FA, Ackman ML, Tsuyuki RT, Kimber S, Teo KK. Contemporary utilization of digoxin in patients with atrial fibrillation. Ann Pharmacother. 1999;33(3):289-293.

30. Thiem U, Lamsfuß R, Günther S, Schumacher J, Bäker C, Endres HG, Zacher J, Burmester GR, Pientka L. Prevalence of Self-Reported Pain, Joint Complaints and Knee or Hip Complaints in Adults Aged≥ 40 Years: A Cross-Sectional Survey in Herne, Germany. PLoS One. 2013;8(4):e60753. doi: 10.1371/journal.pone.0060753

31. Mahé I, Bertrand N, Drouet L, Bal Dit Sollier C, Simoneau G, Mazoyer E, Caulin C, Bergmann JF. between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621-1627.

32. Launiainen T, Sajantila A, Rasanen I, Vuori E, Ojanpera I. Adverse interaction of warfarin and paracetamol: evidence from a post-mortem study. Eur J Clin Pharmacol. 2010;66(1):97-103. doi: 10.1007/s00228-009-0727-3

33. Lamberts M, Lip GY, Hansen ML, Lindhardsen J, Olesen JB, Raunsø J, Olsen AM, Andersen PK, Gerds TA, Fosbøl EL, Torp-Pedersen C, Gislason GH. Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study. Ann Intern Med. 2014;161(10):690-698. doi: 10.7326/M13-1581

34. Bajorek BV, Ogle SJ, Duguid MJ, Shenfield GM, Krass I. Balancing risk versus benefit: the elderly patient’s perspective on warfarin therapy. Pharm Pract (Granada). 2009;7(2):113-123.

35. de Souto Barreto P, Lapeyre-Mestre M, Mathieu C, Piau C, Bouget C, Cayla F, Vellas B, Rolland Y. Prevalence and associations of the use of proton-pump inhibitors in nursing homes: a cross-sectional study. J Am Med Dir Assoc. 2013;14(4):265-269. doi: 10.1016/j.jamda.2012.10.018

36. Jarchow-Macdonald AA, Mangoni AA. Prescribing patterns of proton pump inhibitors in older hospitalized patients in a Scottish health board. Geriatr Gerontol Int. 2013;13(4):1002-1009. doi: 10.1111/ggi.12047

37. sanofi-aventis australia pty ltd. Product Information Omeprazole. 2012. http://wwwmedicinesorgau/files/swpomeprpdf (accessed June 16, 2015).

38. Wang Y, Bajorek B. New Oral Anticoagulants in Practice: Pharmacological and Practical Considerations. Am J Cardiovasc Drugs. 2014;14(3):175-189. doi: 10.1007/s40256-013-0061-0

39. Windle A, Elliot E, Duszynski K, Moore V. Benzodiazepine prescribing in elderly Australian general practice patients. Aust N Z J Public Health. 2007;31(4):379-381.

40. Hayes BD, Klein-Schwartz W, Barrueto F. Polypharmacy and the geriatric patient. Clin Geriatr Med. 2007;23(2):371-390.

41. Caldeira D, Costa J, Fernandes RM, Pinto FJ, Ferreira JJ. Performance of the HAS-BLED high bleeding-risk category, compared to ATRIA and HEMORR2HAGES in patients with atrial fibrillation: a systematic review and meta-analysis. J Interv Card Electrophysiol. 2014 Sep;40(3):277-84. doi: 10.1007/s10840-014-9930-y

42. Bajorek BV, Masood N, Krass I. Development of a Computerised Antithrombotic Risk Assessment Tool (CARAT) to optimise therapy in older persons with atrial fibrillation. Australas J Ageing. 2012;31(2):102-109. doi: 10.1111/j.1741-6612.2011.00546.x

43. Onder G, Liperoti R, Fialova D, Topinkova E, Tosato M, Danese P, Gallo PF, Carpenter I, Finne-Soveri H, Gindin J, Bernabei R, Landi F; SHELTER Project. Polypharmacy in nursing home in Europe: results from the SHELTER study. J Gerontol A Biol Sci Med Sci. 2012;67(6):698-704. doi: 10.1093/gerona/glr233

44. Strehblow C, Smeikal M, Fasching P. Polypharmacy and excessive polypharmacy in octogenarians and older acutely hospitalized patients. Wien Klin Wochenschr. 2014;126(7-8):195-200. doi: 10.1007/s00508-013-0485-1

45. Jyrkka J, Enlund H, Korhonen MJ, Sulkava R, Hartikainen S. Patterns of drug use and factors associated with polypharmacy and excessive polypharmacy in elderly persons: results of the Kuopio 75+ study: a cross-sectional analysis. Drugs Aging. 2009;26(6):493-503. doi: 10.2165/00002512-200926060-00006

46. Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J; CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362(9386):777-781.

47. Turner JP, Shakib S, Singhal N, Hogan-Doran J, Prowse R, Johns S, Bell JS. Prevalence and factors associated with polypharmacy in older people with cancer. Support Care Cancer. 2014;22(7):1727-1734. doi: 10.1007/s00520-014-2171-x

48. Onder G, Gambassi G, Scales CJ, Cesari M, Vedova CD, Landi F, Bernabei R. Adverse drug reactions and cognitive function among hospitalized older adults. Eur J Clin Pharmacol. 2002;58(5):371-377.

49. Onder G, Lattanzio F, Battaglia M, Cerullo F, Sportiello R, Bernabei R, Landi F. The risk of adverse drug reactions in older patients: beyond drug metabolism. Curr Drug Metab. 2011;12(7):647-651.

50. Australian Government Department of Human Services. Home Medicines Review (HMR). http://wwwmedicareaustraliagovau/provider/pbs/fourth-agreement/hmrjsp (accessed July 01, 2014).

51. Castelino RL, Bajorek BV, Chen TF. Retrospective evaluation of home medicines review by pharmacists in older Australian patients using the medication appropriateness index. Ann Pharmacother. 2010;44(12):1922-1929. doi: 10.1345/aph.1P373

52. The Fifth Community Pharmacy Agreement. MedsCheck & Diabetes MedsCheck. http://5cpacomau/programs/medication-management-initiatives/medscheck-diabetes-medscheck/ (accessed July 01, 2014).

53. Pharmaceutical Society of Australia. Guidelines for pharmacists providing medicines use review (MedsCheck) and diabetes medication management (Diabetes MedsCheck) services. 2012. http://wwwpsaorgau/download/guidelines/3612-medscheck-guidelines-cpdf (accessed Cited June 16, 2015).

54. John E. Ware. SF-36® Health Survey Update. http://wwwsf-36org/tools/sf36shtml (accessed July 01, 2014).
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