Addressing Multimorbidity and Polypharmacy in Individuals With Atrial Fibrillation
Purpose of Review
The objectives of this review were to (1) discuss how multimorbidity and polypharmacy contributes to the complexity of management among individuals with AF and (2) identify any interventions to manage polypharmacy in relation to AF.
Based on the four landmark clinical trials of novel anticoagulants, the most common comorbidities with AF are hypertension, heart failure, diabetes, stroke and myocardial infarction. Polypharmacy was also found prevalent in 76.5% of patients with AF, with a median of six drugs per patient. Despite the consequences of polypharmacy in AF, there is very little evidence-based intervention designed to manage it. Hence, there is a need for further research to examine interventions to manage polypharmacy in relation to AF.
Atrial fibrillation (AF) is the most common type of cardiac arrhythmia requiring treatment in adults. Due to the structural and/or electrophysiological abnormalities that occur in AF, patients are managed through the use of prophylactic anticoagulant and rate and/or rhythm control medications. However, these medications are considered high risk and can increase the chances of medication misadventure. Additionally, AF rarely occurs in isolation and is known to coexist with multiple other medical comorbidities, i.e. multimorbidity. This also increases the number of medications, i.e. polypharmacy and pill burden which results in treatment non-compliance to prescribed therapy.
KeywordsAtrial fibrillation Multimorbidity Polypharmacy Anticoagulation Warfarin
Dr. Caleb Ferguson received funding through the University of Technology Sydney Chancellor’s Postdoctoral Research Fellowship scheme (2016-2017).
Compliance with Ethical Standards
Conflict of Interest
Fahad Shaikh, Lachlan B. Pasch, Phillip J. Newton, Beata V. Bajorek, and Caleb Ferguson declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as • Of importance •• Of major importance
- 6.January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al. 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):e1–76. https://doi.org/10.1016/j.jacc.2014.03.022.CrossRefPubMedGoogle Scholar
- 11.• Wang Y, Singh S, Bajorek B. Old age, high risk medication, polypharmacy: a “trilogy” of risks in older patients with atrial fibrillation. Pharm Pract (Granada). 2016;14(2):706. https://doi.org/10.18549/PharmPract.2016.02.706. This study identified that polypharmacy can increase the risk of medication misadvernture in individuals with atrial fibrillation. CrossRefGoogle Scholar
- 15.Nobili A, Marengoni A, Tettamanti M, Salerno F, Pasina L, Franchi C, et al. Association between clusters of diseases and polypharmacy in hospitalized elderly patients: results from the REPOSI study. Eur J Intern Med. 2011;22(6):597–602. https://doi.org/10.1016/j.ejim.2011.08.029.CrossRefPubMedGoogle Scholar
- 16.Piccini JP, Hellkamp AS, Washam JB, Becker RC, Breithardt G, Berkowitz SD, et al. Polypharmacy and the efficacy and safety of rivaroxaban versus warfarin in the prevention of stroke in patients with nonvalvular atrial fibrillation. Circulation. 2016;133(4):352–60. https://doi.org/10.1161/circulationaha.115.018544.CrossRefPubMedGoogle Scholar
- 19.Jaspers Focks J, Brouwer MA, Wojdyla DM, Thomas L, Lopes RD, Washam JB, et al. Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial. BMJ. 2016;353:i2868. https://doi.org/10.1136/bmj.i2868.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Australia NHFo. Guideline for the diagnosis and management of hypertension in adults. National Heart Foundation of Australia. 2016.Google Scholar
- 31.Denolin H, Kuhn H, Krayenbuehl H, Loogen F, Reale A. The defintion of heart failure. Eur Heart J. 1983;4(7):445–8. https://doi.org/10.1093/oxfordjournals.eurheartj.a061500.CrossRefPubMedGoogle Scholar
- 32.Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)developed with the special contribution of the heart failure association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129–200. https://doi.org/10.1093/eurheartj/ehw128.CrossRefPubMedGoogle Scholar
- 37.National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand (Chronic Heart Failure Guidelines Expert Writing Panel). Guidelines for the prevention, detection and management of chronic heart failure in Australia. 2011.Google Scholar
- 38.Silva-Cardoso J, Zharinov OJ, Ponikowski P, Naditch-Brûlé L, Lewalter T, Brette S, et al. Heart failure in patients with atrial fibrillation is associated with a high symptom and hospitalization burden: the RealiseAF survey. Clin Cardiol. 2013;36(12):766–74. https://doi.org/10.1002/clc.22209.CrossRefPubMedGoogle Scholar
- 39.Wongcharoen W, S-A C. The pathophysiology of atrial fibrillation in heart failure. J Innov Cardiac Rhythm Manag. 2012;3:865–9.Google Scholar
- 50.Authors/Task Force M, Ryden L, Grant PJ, Anker SD, Berne C, Cosentino F, et al. ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of diabetes (EASD). Eur Heart J. 2013;34(39):3035–87. https://doi.org/10.1093/eurheartj/eht108.CrossRefGoogle Scholar
- 54.Jespersen SF, Christensen LM, Christensen A, Christensen H. Increasing rate of atrial fibrillation from 2003 to 2011 in patients with ischaemic stroke: results from 55,551 patients in a nationwide registry. Eur J Neurol. 2015;22(5):839–44. https://doi.org/10.1111/ene.12671.CrossRefPubMedGoogle Scholar
- 60.Violi F, Soliman EZ, Pignatelli P, Pastori D. Atrial fibrillation and myocardial infarction: a systematic review and appraisal of pathophysiologic mechanisms. J Am Heart Assoc. 2016;5(5). https://doi.org/10.1161/JAHA.116.003347.
- 66.•• Ferguson C, Inglis SC, Newton PJ, Middleton S, Macdonald PS, Davidson PM. Multi-morbidity, frailty and self-care: important considerations in treatment with anticoagulation drugs. Outcomes of the AFASTER study. Eur J Cardiovasc Nurs. 2017;16(2):113–24. https://doi.org/10.1177/1474515116642604. This study highlighted that multi-morbidity, frailty and self-care as important considerations in anticoagulation decision-making. CrossRefPubMedGoogle Scholar
- 67.Hu Y-F, Liao J-N, Chern C-M, Weng C-H, Lin Y-J, Chang S-L, et al. Identification and management of noncompliance in atrial fibrillation patients receiving dabigatran: the role of a drug monitor. Pacing Clin Electrophysiol: PACE. 2015;38(4):465–71. https://doi.org/10.1111/pace.12575.CrossRefPubMedGoogle Scholar
- 68.•• Patterson SM, Cadogan CA, Kerse N, Cardwell CR, Bradley MC, Ryan C et al. Interventions to improve the appropriate use of polypharmacy for older people. Cochrane Database Syst Rev. 2014(10):CD008165. https://doi.org/10.1002/14651858.CD008165.pub3. This Cochrane review revealed that interventions such as pharmaceutical care appears to be beneficial to reduce inappropriate prescribing and medication related problems.
- 69.Ahmad A, Hugtenburg J, Welschen LM, Dekker JM, Nijpels G. Effect of medication review and cognitive behaviour treatment by community pharmacists of patients discharged from the hospital on drug related problems and compliance: design of a randomized controlled trial. BioMedCentral Public Health. 2010;10(133):1–10.Google Scholar
- 71.Hanley CM, Kowey PR. Are the novel anticoagulants better than warfarin for patients with atrial fibrillation? J Thorac Dis. 2015;7(2):165–71. https://doi.org/10.3978/j.issn.2072-1439.2015.01.23.PubMedPubMedCentralGoogle Scholar
- 72.Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955–62. https://doi.org/10.1016/s0140-6736(13)62343-0.CrossRefPubMedGoogle Scholar
- 74.Ferguson C, Inglis SC, Newton PJ, Middleton S, Macdonald PS, Davidson PM. Atrial fibrillation and thromboprophylaxis in heart failure: the need for patient-centered approaches to address adherence. Vasc Health Risk Manag. 2013;9:3–11. https://doi.org/10.2147/VHRM.S39571.CrossRefPubMedPubMedCentralGoogle Scholar
- 76.Chan P, Grindrod KA, Bougher D, Pasutto FM, Wilgosh C, Eberhart G, et al. A systematic review of remuneration systems for clinical pharmacy care services. Can Pharm J / Rev Pharm Can. 2008;141(2):102–12. https://doi.org/10.3821/1913701X2008141102ASRORS20CO2.Google Scholar