Polypharmacy Patterns: Unravelling Systematic Associations between Prescribed Medications

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Abstract

Objectives

The aim of this study was to demonstrate the existence of systematic associations in drug prescription that lead to the establishment of patterns of polypharmacy, and the clinical interpretation of the associations found in each pattern.

Methods

A cross-sectional study was conducted based on information obtained from electronic medical records and the primary care pharmacy database in 2008. An exploratory factor analysis of drug dispensing information regarding 79,089 adult patients was performed to identify the patterns of polypharmacy. The analysis was stratified by age and sex.

Results

Seven patterns of polypharmacy were identified, which may be classified depending on the type of disease they are intended to treat: cardiovascular, depression-anxiety, acute respiratory infection (ARI), chronic obstructive pulmonary disease (COPD), rhinitis-asthma, pain, and menopause. Some of these patterns revealed a clear clinical consistency and included drugs that are prescribed together for the same clinical indication (i.e., ARI and COPD patterns). Other patterns were more complex but also clinically consistent: in the cardiovascular pattern, drugs for the treatment of known risk factors—such as hypertension or dyslipidemia—were combined with other medications for the treatment of diabetes or established cardiovascular pathology (e.g., antiplatelet agents). Almost all of the patterns included drugs for preventing or treating potential side effects of other drugs in the same pattern.

Conclusions

The present study demonstrated the existence of non-random associations in drug prescription, resulting in patterns of polypharmacy that are sound from the pharmacological and clinical viewpoints and that exist in a significant proportion of the population. This finding necessitates future longitudinal studies to confirm some of the proposed causal associations. The information discovered would further the development and/or adaptation of clinical patient guidelines to patients with multimorbidity who are taking multiple drugs.

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Most cited references 29

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General cardiovascular risk profile for use in primary care: the Framingham Heart Study.

Ralph B. D’Agostino, Ramachandran S Vasan, Michael J Pencina … (2008)

Separate multivariable risk algorithms are commonly used to assess risk of specific atherosclerotic cardiovascular disease (CVD) events, ie, coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. The present report presents a single multivariable risk function that predicts risk of developing all CVD and of its constituents. We used Cox proportional-hazards regression to evaluate the risk of developing a first CVD event in 8491 Framingham study participants (mean age, 49 years; 4522 women) who attended a routine examination between 30 and 74 years of age and were free of CVD. Sex-specific multivariable risk functions ("general CVD" algorithms) were derived that incorporated age, total and high-density lipoprotein cholesterol, systolic blood pressure, treatment for hypertension, smoking, and diabetes status. We assessed the performance of the general CVD algorithms for predicting individual CVD events (coronary heart disease, stroke, peripheral artery disease, or heart failure). Over 12 years of follow-up, 1174 participants (456 women) developed a first CVD event. All traditional risk factors evaluated predicted CVD risk (multivariable-adjusted P<0.0001). The general CVD algorithm demonstrated good discrimination (C statistic, 0.763 [men] and 0.793 [women]) and calibration. Simple adjustments to the general CVD risk algorithms allowed estimation of the risks of each CVD component. Two simple risk scores are presented, 1 based on all traditional risk factors and the other based on non-laboratory-based predictors. A sex-specific multivariable risk factor algorithm can be conveniently used to assess general CVD risk and risk of individual CVD events (coronary, cerebrovascular, and peripheral arterial disease and heart failure). The estimated absolute CVD event rates can be used to quantify risk and to guide preventive care.

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Adverse drug events in ambulatory care.

Tejal Gandhi, Saul N Weingart, Joshua Borus … (2003)

Adverse events related to drugs occur frequently among inpatients, and many of these events are preventable. However, few data are available on adverse drug events among outpatients. We conducted a study to determine the rates, types, severity, and preventability of such events among outpatients and to identify preventive strategies. We performed a prospective cohort study, including a survey of patients and a chart review, at four adult primary care practices in Boston (two hospital-based and two community-based), involving a total of 1202 outpatients who received at least one prescription during a four-week period. Prescriptions were computerized at two of the practices and handwritten at the other two. Of the 661 patients who responded to the survey (response rate, 55 percent), 162 had adverse drug events (25 percent; 95 percent confidence interval, 20 to 29 percent), with a total of 181 events (27 per 100 patients). Twenty-four of the events (13 percent) were serious, 51 (28 percent) were ameliorable, and 20 (11 percent) were preventable. Of the 51 ameliorable events, 32 (63 percent) were attributed to the physician's failure to respond to medication-related symptoms and 19 (37 percent) to the patient's failure to inform the physician of the symptoms. The medication classes most frequently involved in adverse drug events were selective serotonin-reuptake inhibitors (10 percent), beta-blockers (9 percent), angiotensin-converting-enzyme inhibitors (8 percent), and nonsteroidal antiinflammatory agents (8 percent). On multivariate analysis, only the number of medications taken was significantly associated with adverse events. Adverse events related to drugs are common in primary care, and many are preventable or ameliorable. Monitoring for and acting on symptoms are important. Improving communication between outpatients and providers may help prevent adverse events related to drugs. Copyright 2003 Massachusetts Medical Society

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Causes and consequences of comorbidity: a review.

R Gijsen, N Hoeymans, F. G. Schellevis … (2001)

A literature search was carried out to identify and summarize the existing information on causes and consequences of comorbidity of chronic somatic diseases. A selection of 82 articles met our inclusion criteria. Very little work has been done on the causes of comorbidity. On the other hand, much work has been done on consequences of comorbidity, although comorbidity is seldom the main subject of study. We found comorbidity in general to be associated with mortality, quality of life, and health care. The consequences of specific disease combinations, however, depended on many factors. We recommend more etiological studies on shared risk factors, especially for those comorbidities that occur at a higher rate than expected. New insights in this field can lead to better prevention strategies. Health care workers need to take comorbid diseases into account in monitoring and treating patients. Future studies on consequences of comorbidity should investigate specific disease combinations.

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Author and article information

Contributors

Alfonso Carvajal: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2013

Publication date (Electronic): 20 December 2013

Volume: 8

Issue: 12

Electronic Location Identifier: e84967

Affiliations

[1 ]EpiChron Research Group on Chronic Diseases, Aragón Health Sciences Institute (IACS), IIS Aragón, Miguel Servet University Hospital, Zaragoza, Spain

[2 ]Department of Microbiology, Preventive Medicine and Public Health, University of Zaragoza, Zaragoza, Spain

[3 ]Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Carlos III Health Institute, Madrid, Spain

[4 ]Teaching Unit of Preventive Medicine and Public Health, Aragón Health Sciences Institute (IACS), IIS Aragón, Zaragoza, Spain

[5 ]San Pablo Health Centre, Zaragoza, Spain

[6 ]Delicias Sur Health Centre, Zaragoza, Spain

[7 ]Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, Zaragoza, Spain

[8 ]Department of Health Wellbeing and Family, Government of Aragón, Zaragoza, Spain

[9 ]Primary Care Directorate, Aragón Health Service, Zaragoza, Spain

Universidad de Valladolid, Spain

Author notes

* E-mail: acalderon.iacs@ 123456aragon.es

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: ACL APT. Performed the experiments: ACL BPP JMAD APF APT. Analyzed the data: BPP. Contributed reagents/materials/analysis tools: ACL LGF FGR MLS APT. Wrote the manuscript: ACL LGF FGR MLS APT.

Article

Publisher ID: PONE-D-13-07227

DOI: 10.1371/journal.pone.0084967

PMC ID: 3869920

PubMed ID: 24376858

SO-VID: c7b2ccbc-e6f7-47ef-b9fa-8efeca11c8cb

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 15 February 2013

Date accepted : 27 November 2013

Funding

This study was funded by grant PI11/01126 from the Carlos III Health Institute of the Spanish Ministry of Economy and Competitiveness. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Polypharmacy Patterns: Unravelling Systematic Associations between Prescribed Medications

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Abstract

Objectives

Methods

Results

Conclusions

Related collections

PLOS Climate

Most cited references 29

General cardiovascular risk profile for use in primary care: the Framingham Heart Study.

Adverse drug events in ambulatory care.

Causes and consequences of comorbidity: a review.

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Cited by 25

Most referenced authors 661