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Cardiology Research

Review

Volume 15, Number 2, April 2024, pages 75-85

Definition of Polypharmacy in Heart Failure: A Scoping Review of the Literature

A high medication burden is remarkably prevalent among patients with heart failure (HF), both in the inpatient and outpatient setting. The prevalence of a high medication burden in HF patients is increasing as patients are living longer with more chronic medical conditions, and new medications are added to guideline-directed medical therapy (GDMT) [1]. This can lead to drug-drug interactions, poor adherence, adverse reactions, cognitive impairment, and decreased medication compliance [2, 3]. A recent study showed that 84% of HF patients were taking ≥ 5 medications on admission, 95% of HF patients were taking ≥ 5 on discharge, and 55% of HF patients were taking ≥ 10 medications on discharge [4]. A high medication burden is often characterized as polypharmacy; however, there are several definitions of polypharmacy in the literature. Some studies define polypharmacy quantitatively, for example, taking ≥ 5 medications, whereas other studies define polypharmacy qualitatively, for example, a complex drug regimen [5, 6]. Although the definition of polypharmacy in HF patients is often debated, most experts agree that polypharmacy is an underestimated problem in this population [2]. The aims of this review were: 1) to conduct a scoping review to find the most common definition of polypharmacy in HF patients, 2) to assess how the literature defined polypharmacy in this specific group, and 3) to review the impact of polypharmacy on patients with HF.

We conducted a scoping review searching Ovid Medline, Elsevier Embase, CINAHL, and Cochrane Library using terms including polypharmacy, HF, and deprescribing, which resulted in 7,949 articles. The search was conducted in March 2021 (Supplementary Material 1, www.cardiologyres.org). The abstracts of all 7,949 articles were screened by two independent reviewers. Of the 7,949 articles, both reviewers independently agreed on including 117 articles and excluding 7,219 articles. The independent reviewers disagreed on 613 articles, and a third independent reviewer resolved these disputes, ultimately deciding to include 384 of the articles. Of the 7,949 articles, 501 articles passed the initial screening phase. The 501 articles were fully examined, and of those, 59 were included (Fig. 1). Abstracts were included if they defined polypharmacy in HF populations and were written in English. Abstracts were excluded if they did not include a definition for polypharmacy in patients with HF or if they included patients < 18 years of age.

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Figure 1. Article selection criteria for the scoping review.

Of the 59 articles, 48% (n = 29) were retrospective, 20% (n = 12) were prospective, 10% (n = 6) were cross-sectional, and 27% (n = 16) were review articles (Table 1) [2-59]. Of note, some of the articles fit into more than one category. Twenty percent (n = 12) of the articles focused on HF with reduced ejection fraction (HFrEF), 10% (n = 6) focused on HF with preserved ejection fraction (HFpEF), and 69% (n = 41) articles either focused on both diagnoses or did not clarify the specific type of HF. The most common cardiovascular comorbidities identified in these articles were hypertension, diabetes, dyslipidemia, ischemic heart disease, and atrial fibrillation.

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Table 1. Articles Used for Scoping Review, Their Definitions, Study Types and Details in the Study

The majority of articles defined polypharmacy quantitatively. The most common cutoff for polypharmacy in HF was five medications (58%, n = 35) and the second most common cutoff for polypharmacy in HF was 10 medications (14%, n = 8). Furthermore, several articles also used the definition of hyperpolypharmacy or excessive polypharmacy with a cutoff value of 10 medications, apart from the definition of polypharmacy. Furthermore, one study by Kinugasa et al used the mean number of medications in the study cohort as the definition of polypharmacy [59].

Although we planned this review with the aim to identify a quantitative definition of polypharmacy, we recognized that some articles only defined polypharmacy in HF qualitatively (n = 6). For example, the common qualitative definitions included themes such as complex medication regimens and a high medication burden. Also, several studies used both quantitative and qualitative nuance to define polypharmacy such as “the use of multiple medications in a complex drug regimen” or “prescription of multiple drugs concurrently.” This is a finding that we did not expect, but these mixed definitions were commonly used.

While reviewing the literature, we also found that more than half of the articles (55%, n = 33) that we reviewed did not specify their rationale of using such definition of polypharmacy. It reflects that the definition of polypharmacy has been used somewhat arbitrarily by the authors without scientific evidence.

Throughout the review, we realized that there was no consensus regarding the inclusion or exclusion of over-the-counter (OTC) medications, supplements, or vitamins. However, the most common medications at both admission and discharge were non-cardiovascular and included proton-pump inhibitors, electrolyte supplements, and multivitamins [4]. There was no consensus regarding the inclusion or exclusion of as-needed medications, medications that were required for a short duration, or chronically prescribed medication.

As one of the leading causes of high mortality and morbidity, HF mainly affects older adults, evidenced by that more than half of patients with HF in the USA are 75 years or older [60]. In the last decade, GDMT for HF has introduced many medications with survival benefits, recommending a combination of multiple medications for optimal management of HF [61-63]. Such combinations of medications have shown clinical benefits in multiple randomized controlled trials, but in the real world, medications also create problems in older adults. These problems include a high prevalence of medication-related issues including medication errors, non-adherence, drug-drug or drug-disease interactions, and adverse drug effects. Such medication-related problems could be associated with adverse clinical outcomes and compromise each medication’s expected survival benefit among older adults with HF [64-66]. The patient’s pre-existing mental or physical limitations can also intensify the impacts of polypharmacy such as medication errors, non-adherence or prescribing cascade [67-69].

Therefore, identifying polypharmacy and its predicted impact on the pharmacotherapy of HF for older adults is crucial in real-world practice. However, the true impact of polypharmacy may not only come from the number of the medications, but also from other factors in the context of polypharmacy.

It is obvious that the number of medications should be one of the most important factors to consider. It has been well documented that the number of medications is associated with adverse clinical impact on older adults. For example, a study showed that a person taking five or seven medications has a high risk of adverse drug reactions of 58% and 82% respectively, compared to 13% for a person taking two medications [70].

Older adults with HF are not only prescribed many medications, but also instructed to take them with a complex schedule. For example, beta-blockers may be prescribed twice a day, angiotensin-converting enzyme inhibitors once a day and diuretics as needed. Although such complex regimens were proven to be effective collectively, the true benefit of the regimen depends on the patient’s adherence [71]. Therefore, when we define polypharmacy, the complexity of regimen also should be accounted for.

When patients have multiple medical conditions, a situation when one medication for one medical condition may be contraindicated for another medical condition may occur (therapeutic competition) [72, 73]. Or, the two medications interact with each other to weaken the clinical benefit of one or worsen the side effect of one. Therefore, when we define polypharmacy to assess its impact on patients, consideration of drug-drug interactions should be accounted for [71].

Consideration to pre-existing conditions within older patients who medicate for HF may require greater attention, when discussing polypharmacy. Mental, physical, or other life-influencing hardships may cause a patient to take less than prescribed dosages, alter medication frequencies, or forego consumption completely [7]. For example, dementia will affect the older adult’s ability to remember the medication schedule. Physical impairment may affect the older patient’s capability to drive to pick up the medications. Or, older adults with other life-threatening medical condition may also decide not to take medications for other medical conditions. Therefore, when defining polypharmacy, such drug-disease interactions, especially drug-geriatric syndromes, should also be considered.

In summation, the devising of medication regimens in older patients with HF should be proactive. Accounting for a patient’s pre-existing conditions, economic background, and daily support measures are of high significance in mitigating polypharmacy, attempts to manage consequences of polypharmacy after the fact levy further complications for older adults with HF. Unforeseen conflicts with patient comorbidities, ability to begin and maintain medication regimens, and possible contraindications between drugs can be associated with polypharmacy and further impact overall clinical benefit. With polypharmacy more thoroughly defined and considered during pharmacotherapy, patient treatment plans may be optimized and the expected clinical benefit may be maximized [71].

From our scoping review, we found out that most studies define polypharmacy in HF quantitatively and the most common cutoff for polypharmacy in HF was five medications (58%, n = 35). The second most common cutoff was 10 medications (14%, n = 8). Nevertheless, there were many discrepancies on what medications to include. It is unclear if short-term, OTC, or as needed medications should be included in the definition of polypharmacy. It is also unclear if polypills, for example, sacubitril-valsartan, should be counted as one medication or several when defining polypharmacy. Further discussions of polypills when accounting for the polypharmacy should be done, since recent studies have shown that polypills decrease pill burden and may increase compliance by decreasing medication regimen complexity [74].

Another factor that is often not discussed regarding polypharmacy is the frequency of dosing. Providers should be cautious with medications that need to be taken more than once a day. Studies have shown that the number of doses per day is inversely related to compliance [75]. In some cases, what matters more to the patient’s compliance could be the frequency of dosing rather than the number of pills. Providers should consider reducing medication frequency whenever appropriate for a simpler medication regime.

Polypharmacy disproportionally affects certain populations, and higher rates of polypharmacy are seen in low socioeconomic status patients. For example, low income and low educational level are independently associated with higher rates of polypharmacy in patients with HF and low-income patients also have lower rates of GDMT, one example of suboptimal prescribing with both underutilization (lower rates of GDMT) and overutilization of medications (higher rates of polypharmacy) concurrently [8, 76].

Providers should pay close attention to patients with advanced HF [9]. Most HF studies are done on healthier patients, and therefore these medications may not have the same benefit-risk profile with advanced HF and a poor prognosis [10]. These patients should be seen by HF and palliative care specialists. Although palliative care providers may increase polypharmacy in this population, they improve the patient’s quality of life [77]. Providers should consider deprescribing prophylactic and life-prolonging medications in advanced HF patients with a limited life expectancy while allowing for “appropriate polypharmacy” and an emphasis on medications that improve quality of life [9, 77]. In appropriate polypharmacy, patients may be taking more than five or 10 medications; however, the medications are appropriate and evidence-based. In appropriate polypharmacy, the benefit of polypharmacy outweighs the risks.

As HF management evolves, the definition of polypharmacy in this patient population may also need to adapt. For example, HFrEF GDMT includes at least four or five different medication classes depending on the patient’s condition, including beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors. If the HFrEF is secondary to ischemia, antiplatelet and lipid-lowering medications may also be indicated. Additionally, HF patients often have other comorbidities, such as diabetes mellitus and chronic obstructive pulmonary disease, that require treatment with additional medications. If we use the cutoff value of 5 for the definition of polypharmacy, the majority of the HF patients would have polypharmacy, and the distinguishing power of polypharmacy would become low. Therefore, when we define polypharmacy in HF patients, whether we also should include the essential GDMT medications or not becomes a question. However, our review revealed that most of the definitions of polypharmacy used the total number of medications regardless of the classification of the medications. Furthermore, because of the same reason that GDMT itself induces polypharmacy, recognizing that those essential medications are included in polypharmacy is important. When considering discontinuation of medications in HF patients, it may be helpful to view medications in a hierarchical manner based on the patient’s comorbidities, focusing on removing medications with little to no benefit, while continuing life prolonging medications. For example, when we consider deprescribing, we should focus on non-GDMT medications first, since GDMT medications are still essential and critical for survival and clinical benefits for HF management.

A recent systemic review also found that the most common definition of polypharmacy in patients with HF was ≥ 5 medications [78]. Our scoping review had several differences compared to Beezer et al, including a larger sample size of 59 articles compared to 22 articles and inclusion of conference abstracts. While the authors agree with us on the need for a consensus definition, they believe it is unclear whether a qualitative or quantitative definition is more appropriate [78]. Based on our scoping review, we argue that a quantitative definition of polypharmacy in HF is more appropriate with a cutoff of ≥ 10 medications.

There are several limitations to this study. We included articles ranging from the years 2000 to 2020. As medication management of HF evolves and new medications are included in GDMT, older articles may not be as relevant. We also excluded any articles that were not published in English, so we may have missed relevant articles. We also included articles regardless of the quality of the study.

In summary, polypharmacy can lead to drug interactions, cognitive impairment, medication non-compliance, and falls. Based on our scoping review, the most common definition of polypharmacy in HF was the use of ≥ 5 medications. Due to the increase in GDMT, life expectancy, and the number of medical comorbidities, most patients with HF use ≥ 5 medications. Although a cutoff of five medications indicates an increased risk of adverse effects, a cutoff of 10 medications captures the highest risk. Increasing the cutoff to 10 medications will emphasize removing unnecessary and harmful medications and preventing discontinuation of beneficial medications. As patients with HF are living longer, providers must be sensitive to geriatric conditions and the risk of adverse events as polypharmacy is common in this population. We agree that providers should pay close attention to those patients taking ≥ 10 medications, but most importantly, providers should make sure that every agent being used has a favorable risk-to-benefit ratio.

Suppl 1. Search terms.

Acknowledgments

None to declare.

Financial Disclosure

This study was not supported by any sponsor or funder.

Conflict of Interest

The authors have no conflict of interest to declare.

Author Contributions

KP was involved in the conceptualization, data curation, and original draft preparation. JAI was involved in data curation and editing the draft. AK was involved in data curation and editing the draft. DS was involved in data interpretation and editing the draft. TH was involved in conceptualization, methodology, data curation, reviewing and editing the draft. PG was involved in reviewing and editing the draft. MJK was involved in conceptualization, methodology, data curation, reviewing and editing the draft, and supervision.

Data Availability

The authors declare that data supporting the findings of this study are available within the article.

Abbreviations

HF: heart failure; GDMT: guideline-directed medical therapy; OTC: over-the-counter

1. Wong CY, Chaudhry SI, Desai MM, Krumholz HM. Trends in comorbidity, disability, and polypharmacy in heart failure. Am J Med. 2011;124(2):136-143.
   doi pubmed pmc
2. Mastromarino V, Casenghi M, Testa M, Gabriele E, Coluccia R, Rubattu S, Volpe M. Polypharmacy in heart failure patients. Curr Heart Fail Rep. 2014;11(2):212-219.
   doi pubmed
3. Salyer J, Sargent L, Tirado C, Flattery MP, Shah KB. Anticholinergic burden and cognitive impairment in patients with heart failure. The Journal of Heart and Lung Transplantation. 2019;38(4):S299.
   doi
4. Unlu O, Levitan EB, Reshetnyak E, Kneifati-Hayek J, Diaz I, Archambault A, Chen L, et al. Polypharmacy in older adults hospitalized for heart failure. Circ Heart Fail. 2020;13(11):e006977.
   doi pubmed pmc
5. Rich MW. Pharmacotherapy of heart failure in the elderly: adverse events. Heart Fail Rev. 2012;17(4-5):589-595.
   doi pubmed
6. Georgiev KD, Hvarchanova N, Georgieva M, Kanazirev B. The role of the clinical pharmacist in the prevention of potential drug interactions in geriatric heart failure patients. Int J Clin Pharm. 2019;41(6):1555-1561.
   doi pubmed
7. Baron-Franco B, McLean G, Mair FS, Roger VL, Guthrie B, Mercer SW. Comorbidity and polypharmacy in chronic heart failure: a large cross-sectional study in primary care. Br J Gen Pract. 2017;67(658):e314-e320.
   doi pubmed pmc
8. Kennel PJ, Kneifati-Hayek J, Bryan J, Banerjee S, Sobol I, Lachs MS, Safford MM, et al. Prevalence and determinants of Hyperpolypharmacy in adults with heart failure: an observational study from the National Health and Nutrition Examination Survey (NHANES). BMC Cardiovasc Disord. 2019;19(1):76.
   doi pubmed pmc
9. Barcelo M, Torres O, Ruiz D, Casademont J. Appropriateness of medications prescribed to elderly patients with advanced heart failure and limited life expectancy who died during hospitalization. Drugs Aging. 2014;31(7):541-546.
   doi pubmed
10. Bader F, Atallah B, Brennan LF, Rimawi RH, Khalil ME. Heart failure in the elderly: ten peculiar management considerations. Heart Fail Rev. 2017;22(2):219-228.
    doi pubmed
11. Albert NM. Switching to once-daily evidence-based [beta]-blockers in patients with systolic heart failure or left ventricular dysfunction after myocardial infarction. Crit Care Nurse. 2007;27(6):62-72.
    pubmed
12. Abbas S, Ihle P, Harder S, Schubert I. Risk of hyperkalemia and combined use of spironolactone and long-term ACE inhibitor/angiotensin receptor blocker therapy in heart failure using real-life data: a population- and insurance-based cohort. Pharmacoepidemiol Drug Saf. 2015;24(4):406-413.
    doi pubmed
13. Lina B, McNamara Jennifer L, Matthew K, et al. Polypharmacy and potentially inappropriate medication use are universal among patients with heart failure with preserved ejection fraction. J Am Coll Cardiol. 2019;73(9):852.
    doi
14. Brinker LM, Konerman MC, Navid P, Dorsch MP, McNamara J, Willer CJ, Tinetti ME, et al. Complex and potentially harmful medication patterns in heart failure with preserved ejection fraction. Am J Med. 2021;134(3):374-382.
    doi pubmed pmc
15. Altunbas G, Yazc M, Solak Y, Gul EE, Kayrak M, Kaya Z, Akilli H, et al. Renal drug dosage adjustment according to estimated creatinine clearance in hospitalized patients with heart failure. Am J Ther. 2016;23(4):e1004-1008.
    doi pubmed
16. Alvarez PA, Truong CN, Briasoulis A, Ganduglia-Cazaban C. Prescription of potentially harmful drugs in young adults with heart failure and reduced ejection fraction. Am J Cardiol. 2019;123(9):1458-1463.
    doi pubmed
17. Cobretti MR, Page RL, 2nd, Linnebur SA, Deininger KM, Ambardekar AV, Lindenfeld J, Aquilante CL. Medication regimen complexity in ambulatory older adults with heart failure. Clin Interv Aging. 2017;12:679-686.
    doi pubmed pmc
18. De Geest S, Steeman E, Leventhal ME, Mahrer-Imhof R, Hengartner-Kopp B, Conca A, Bernasconi AT, et al. Complexity in caring for an ageing heart failure population: concomitant chronic conditions and age related impairments. Eur J Cardiovasc Nurs. 2004;3(4):263-270.
    doi pubmed
19. Eijsink M, Zeeman M, van Wijngaarden J, Badings E, van’t Riet E. Does polypharmacy in elderly patients with heart failure influence mortality and hospitalisation? Clin Ther. 2015;37(8):e81-e82.
    doi
20. El Hadidi S, Rosano G, Tamargo J, Agewall S, Drexel H, Kaski JC, Niessner A, et al. Potentially inappropriate prescriptions in heart failure with reduced ejection fraction: ESC position statement on heart failure with reduced ejection fraction-specific inappropriate prescribing. Eur Heart J Cardiovasc Pharmacother. 2022;8(2):187-210.
    doi pubmed
21. Bansal K, Rajput SK, Sharma V, Mathur VS. Drug Utilization in HF Patients: Exploring Reasons to Improve Adherence at Tertiary Care Unit. Int J Pharm Res. 2020;12(1).
22. Butrous H, Hummel SL. Heart Failure in Older Adults. Can J Cardiol. 2016;32(9):1140-1147.
    doi pubmed pmc
23. Fentie Wendie T, Tarekegn Angamo M. Drug-therapy problems and predictors among hospitalized heart-failure patients: a prospective observational study. Drug Healthc Patient Saf. 2020;12:281-291.
    doi pubmed pmc
24. Godden J, Waite M. Medicines management in the community: An HF specialist nurse prescriber's experience. British Journal of Cardiac Nursing. 2014;9(9):444-451.
    doi
25. Goyal P, Bryan J, Kneifati-Hayek J, Sterling MR, Banerjee S, Maurer MS, Lachs MS, et al. Association between functional impairment and medication burden in adults with heart failure. J Am Geriatr Soc. 2019;67(2):284-291.
    doi pubmed pmc
26. Guirguis K. Prescribed heart failure pharmacotherapy: How closely do GPs adhere to treatment guidelines? Res Social Adm Pharm. 2020;16(7):935-940.
    doi pubmed
27. Laroche M, Johnell K, Fastbom J, Morin L. Polypharmacy and burden of cardiovascular medications in older adults with heart failure near the end of life. Pharmacoepidemiology and Drug Safety.
28. Parajuli DR, Shakib S, Eng-Frost J, McKinnon RA, Caughey GE, Whitehead D. Evaluation of the prescribing practice of guideline-directed medical therapy among ambulatory chronic heart failure patients. BMC Cardiovasc Disord. 2021;21(1):104.
    doi pubmed pmc
29. Proietti M, Marra A, Salzano A, et al. Heart failure in elderly and very elderly hospitalized patients: an epidemiological analysis from the REPOSI registry. Eur Heart J. 2019;40.
    doi
30. Reed BN, Rodgers JE, Sueta CA. Polypharmacy in heart failure: drugs to use and avoid. Heart Fail Clin. 2014;10(4):577-590.
    doi pubmed
31. Rushton CA, Kadam UT. Polypharmacy in heart failure: a growing challenge. British Journal of Cardiac Nursing. 2011;6(5):214-220.
    doi
32. Sritharan H, Lam J, Dind A, et al. Polypharmacy in patients hospitalised with heart failure: retrospective audit. Heart, Lung and Circulation. 2020;29:S102.
    doi
33. Ozan U, Tina D, Alexi A, et al. Polypharmacy increases in prevalence and severity following a heart failure hospitalization. J Am Coll Cardiol. 2019;73(9):789.
    doi
34. von Lueder TG, Atar D. Comorbidities and polypharmacy. Heart Fail Clin. 2014;10(2):367-372.
    doi pubmed
35. Wu Y, Zhu W, He X, Xue R, Liang W, Wei F, Wu Z, et al. Influence of polypharmacy on patients with heart failure with preserved ejection fraction: a retrospective analysis on adverse outcomes in the TOPCAT trial. Br J Gen Pract. 2021;71(702):e62-e70.
    doi pubmed pmc
36. Kleipool EEF, Wiersinga JHI, Trappenburg MC, van Rossum AC, van Dam CS, Liem SS, Peters MJL, et al. The relevance of a multidomain geriatric assessment in older patients with heart failure. ESC Heart Fail. 2020;7(3):1264-1272.
    doi pubmed pmc
37. Knafl GJ, Riegel B. What puts heart failure patients at risk for poor medication adherence? Patient Prefer Adherence. 2014;8:1007-1018.
    doi pubmed pmc
38. Kumar K, Afonso L. Cardiovascular risk prediction in the elderly. J Geriatr Cardiol. 2019;16(5):414-420.
    doi pubmed pmc
39. Makris E, Hu L, Jones GB, Wright JM. Moving the dial on heart failure patient adherence rates. patient prefer adherence. 2020;14:2407-2418.
    doi pubmed pmc
40. Malouf CA, Ozan U, Evgeniya R, Monika S, Mark L, Parag G. Guideline-directed medical therapy initiation for heart failure with reduced ejection fraction does not vary according to geriatric conditions. J Am Coll Cardiol. 2020;75(11):746.
    doi
41. Martinez-Selles M, Garcia Robles JA, Munoz R, Serrano JA, Frades E, Dominguez Munoa M, Almendral J. Pharmacological treatment in patients with heart failure: patients knowledge and occurrence of polypharmacy, alternative medicine and immunizations. Eur J Heart Fail. 2004;6(2):219-226.
    doi pubmed
42. Masoudi FA, Baillie CA, Wang Y, Bradford WD, Steiner JF, Havranek EP, Foody JM, et al. The complexity and cost of drug regimens of older patients hospitalized with heart failure in the United States, 1998-2001. Arch Intern Med. 2005;165(18):2069-2076.
    doi pubmed
43. Navid P, Zarzuela K, Musse M, et al. Patients with heart failure with preserved ejection fraction contend with deficits across multiple domains of health. Circulation. 2020;142:A15323.
    doi
44. Niriayo YL, Kumela K, Kassa TD, Angamo MT. Drug therapy problems and contributing factors in the management of heart failure patients in Jimma University Specialized Hospital, Southwest Ethiopia. PLoS One. 2018;13(10):e0206120.
    doi pubmed pmc
45. nd Page RL, O'Bryant CL, Cheng D, et al. Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association. Circulation. 2016;134(6):32.
46. Parmley WW. Surviving heart failure: Robert L. Frye lecture. Mayo Clin Proc. 2000;75(1):111-118.
    doi pubmed
47. Ruiz-Laiglesia FJ, Garces-Horna V, Formiga F. Comprehensive therapeutic approach for patients with heart failure and comorbidity. Rev Clin Esp (Barc). 2016;216(6):323-330.
    doi pubmed
48. Harwood TJS, Paoloni RJ, Mitic SS. Accuracy of medication lists on general practitioner referral letters to emergency departments for patients with congestive cardiac failure compared with other polypharmacy patients. J Pharm Pract Res. 2015;45(3):291-296.
    doi
49. Hornsby W, Hatch A, Chun D, et al. Prevalence and clinical implications of frailty in patients referred to a heart failure with preserved ejection fraction clinic. J Card Fail. 2017;23(8):S61.
    doi
50. Jenghua K. Prevalence and associated factors of potentially inappropriate medications among Thai patients with heart failure. Int J Clin Pract. 2021;75(4):e13878.
    doi pubmed
51. Rushton CA, Stromberg A, Jaarsma T, Kadam UT. Multidrug and optimal heart failure therapy prescribing in older general practice populations: a clinical data linkage study. BMJ Open. 2014;4(1):e003698.
    doi pubmed pmc
52. Screever EM, Meijers WC, van Veldhuisen DJ, de Boer RA. New developments in the pharmacotherapeutic management of heart failure in elderly patients: concerns and considerations. Expert Opin Pharmacother. 2017;18(7):645-655.
    doi pubmed
53. Shikata T, Takamoto K, Sakamoto J, et al. The increased number of drugs without guideline recommendation is associated with poor outcome in the patients with chronic heart failure. J Card Fail. 2016;22(9):S163.
    doi
54. Sunaga T, Yokoyama A, Nakamura S, Miyamoto N, Watanabe S, Tsujiuchi M, Nagumo S, et al. Association of potentially inappropriate medications with all-cause mortality in the elderly acute decompensated heart failure patients: importance of nonsteroidal anti-inflammatory drug prescription. Cardiol Res. 2020;11(4):239-246.
    doi pubmed pmc
55. Wammes JJG, Auener S, van der Wees PJ, Tanke MAC, Bellersen L, Westert GP, Atsma F, et al. Characteristics and health care utilization among patients with chronic heart failure: a longitudinal claim database analysis. ESC Heart Fail. 2019;6(6):1243-1251.
    doi pubmed pmc
56. Fujita R, Takabayashi K, Iwatsu K, et al. Prognostic value of polypharmacy in patients with heart failure. Eur Heart J. 2019;40:ehz746.0956.
    doi
57. Haq I, Ismail M, Khan F, Khan Q, Ali Z, Noor S. Prevalence, predictors and outcomes of potential drug-drug interactions in left ventricular failure: considerable factors for quality use of medicines. Brazilian Journal of Pharmaceutical Sciences. 2020;56.
58. Hopper I, de Silva C, Skiba M, Tonkin A, Krum H. Attitudes of patients and prescribing clinicians to polypharmacy and medication withdrawal in heart failure. J Card Fail. 2016;22(9):743-744.
    doi pubmed
59. Kinugasa Y, Nakayama N, Sugihara S, Mizuta E, Nakamura K, Kamitani H, Hirai M, et al. Polypharmacy and taste disorders in heart failure patients. Eur J Prev Cardiol. 2020;27(1):110-111.
    doi pubmed
60. Rich MW. Heart failure in the 21st century: a cardiogeriatric syndrome. J Gerontol A Biol Sci Med Sci. 2001;56(2):M88-96.
    doi pubmed
61. Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, Konstam MA, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14):1977-2016.
    doi pubmed
62. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Jr., Drazner MH, Fonarow GC, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147-239.
    doi pubmed
63. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Jr., Colvin MM, Drazner MH, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137-e161.
    doi pubmed
64. Gastelurrutia P, Benrimoj SI, Espejo J, Tuneu L, Mangues MA, Bayes-Genis A. Negative clinical outcomes associated with drug-related problems in heart failure (HF) outpatients: impact of a pharmacist in a multidisciplinary HF clinic. J Card Fail. 2011;17(3):217-223.
    doi pubmed
65. Volpe M, Chin D, Paneni F. The challenge of polypharmacy in cardiovascular medicine. Fundam Clin Pharmacol. 2010;24(1):9-17.
    doi pubmed
66. Marcum ZA, Amuan ME, Hanlon JT, Aspinall SL, Handler SM, Ruby CM, Pugh MJ. Prevalence of unplanned hospitalizations caused by adverse drug reactions in older veterans. J Am Geriatr Soc. 2012;60(1):34-41.
    doi pubmed pmc
67. Trenaman SC, Bowles SK, Kirkland S, Andrew MK. An examination of three prescribing cascades in a cohort of older adults with dementia. BMC Geriatr. 2021;21(1):297.
    doi pubmed pmc
68. Lim RH, Sharmeen T. Medicines management issues in dementia and coping strategies used by people living with dementia and family carers: A systematic review. Int J Geriatr Psychiatry. 2018;33(12):1562-1581.
    doi pubmed pmc
69. El-Saifi N, Moyle W, Jones C, Tuffaha H. Medication adherence in older patients with dementia: a systematic literature review. J Pharm Pract. 2018;31(3):322-334.
    doi pubmed
70. Davies EA, O'Mahony MS. Adverse drug reactions in special populations - the elderly. Br J Clin Pharmacol. 2015;80(4):796-807.
    doi pubmed pmc
71. Stefil M, Dixon M, Bahar J, Saied S, Mashida K, Heron O, Shantsila E, et al. Polypharmacy in older people with heart failure: roles of the geriatrician and pharmacist. Card Fail Rev. 2022;8:e34.
    doi pubmed pmc
72. Lorgunpai SJ, Grammas M, Lee DS, McAvay G, Charpentier P, Tinetti ME. Potential therapeutic competition in community-living older adults in the U.S.: use of medications that may adversely affect a coexisting condition. PLoS One. 2014;9(2):e89447.
    doi pubmed pmc
73. Kwak MJ, Cheng M, Goyal P, Kim DH, Hummel SL, Dhoble A, Deshmukh A, et al. Medication complexity among older adults with hf: how can we assess better? Drugs Aging. 2022;39(11):851-861.
    doi pubmed pmc
74. Roy A, Naik N, Srinath Reddy K. Strengths and limitations of using the polypill in cardiovascular prevention. Curr Cardiol Rep. 2017;19(5):45.
    doi pubmed pmc
75. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296-1310.
    doi
76. Hung CL, Chao TF, Su CH, Liao JN, Sung KT, Yeh HI, Chiang CE. Income level and outcomes in patients with heart failure with universal health coverage. Heart. 2021;107(3):208-216.
    doi pubmed pmc
77. Granger BB, Tulsky JA, Kaufman BG, Clare RM, Anstrom K, Mark DB, Johnson KA, et al. Polypharmacy in palliative care for advanced heart failure: the PAL-HF experience. J Card Fail. 2022;28(2):334-338.
    doi pubmed pmc
78. Beezer J, Al Hatrushi M, Husband A, Kurdi A, Forsyth P. Polypharmacy definition and prevalence in heart failure: a systematic review. Heart Fail Rev. 2022;27(2):465-492.
    doi pubmed pmc

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