Both New and Chronic Potentially Inappropriate Medications Continued at Hospital Discharge Are Associated with Increased Risk of Adverse Events

Sep 14, 2020   |  Jaideep Patel, MD, FACC; Aaron Jacob Bagnola, PharmD

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  • Nearly half of elderly patients (>65 years of age) were prescribed a new potentially inappropriate medication (PIM); overall, 66% of patients were prescribed a PIM (new and continued) at the time of discharge. The most common newly prescribed PIMs were benzodiazepines, proton pump inhibitors, cyclooxygenase‐2 inhibitors, selective α1 adrenergic blocking agents, opioids, and atypical antipsychotics.
  • Prescription for pre-hospitalization PIMs and new PIMs at the time of discharge was associated with an increased odds of having an adverse drug event within 30 days as well as an increased risk of emergency department visits, hospital readmission, and death.
  • Cardiovascular disease and concomitant geriatric conditions exacerbated the risk of polypharmacy and adverse drug events, supporting the need to increase uptake and expand deprescribing processes to improve clinical care and enhance quality of life.

Editor's Note: Commentary based on Weir DL, Lee TC, McDonald EG, et al. Both new and chronic potentially inappropriate medications continued at hospital discharge are associated with increased risk of adverse events. J Am Geriatr Soc 2020;68:1184-92.

Rationale for Study:
The purpose of this study was to estimate the number of potentially inappropriate medications (PIMs) prescribed to patients at the time of hospital discharge and their association with the risk of adverse events 30 days after discharge.

Funding:
The Canadian Institutes of Health Research funded this study.

Methods:
Abstracted chart data including individual demographic, healthcare service use, and prescription claims from a completed hospital‐based randomized trial of medication reconciliation was linked with the Quebec provincial healthcare administrative database (acquired for the year before hospital admission and the year after discharge). PIMs were identified based on medications found in the AGS Beers Criteria® and STOPP criteria, and drugs listed by Choosing Wisely Canada.1-3 Each medication prescribed at discharge was classified into one of four categories: (1) medications continued from the community (determined using the pharmacy claims database based on dispensations within 3 months of admission and calculated supply) that were not PIMs; (2) PIMs continued from the community; (3) new medications (determined using the discharge prescription found in the patient's chart) that were not PIMs; and (4) new PIMs prescribed at discharge.

Study Design:
Prospective Cohort Study.

Cohort:
Patients aged 65 years or older, admitted to internal medicine, cardiac, and thoracic surgery units, within the McGill University Health Centre Network in Montreal, Quebec, Canada, between October 2014 and November 2016. McGill University Health Centre is made up of two tertiary care academic hospitals.

Exposure:
Hospitalization to an internal medicine, cardiac or thoracic surgery unit.

Outcome(s):
The primary outcome was the occurrence (yes/no) of an adverse drug event (ADE) 30 days after discharge.  A secondary composite outcome was defined as time to the first all‐cause emergency department (ED) visit, rehospitalization, or death in the 30 days after discharge.

Statistical Analysis:
Baseline characteristics of all study patients were reported and stratified by PIMs.  Descriptive statistics were used to summarize the prevalence and characteristics of PIMs prescribed to patients at the time of discharge. Multivariable logistic regression and Cox models were used to assess the association between PIMs and adverse events. Statistical analysis was repeated in a subgroup analyses according to the service the patient was discharged from (medicine vs. surgery).

Results:
The final study population consisted of 2,402 participants (median age 76 years [IQR = 70-82 years], 42.5% female), who were prescribed a median of eight medications at discharge (IQR = 5-10).  A total of 53.6% of patients were discharged from an internal medicine ward. The majority of patients (83%) were discharged home. In total, 1,576 (66%) patients were prescribed at least one PIM at discharge (including both new PIMs and/or those continued from the community). A total of 1,176 (75.0%) patients were re-prescribed at least one of their community PIMs, and 755 (47.9%) were prescribed at least one new PIM. The most common newly prescribed PIMs were benzodiazepines, proton pump inhibitors, cyclooxygenase‐2 inhibitors, selective α‐1 adrenergic blocking agents, opioids, and atypical antipsychotics (7.3%, 4.1%, 3.8%. 3.5%, 2%, and 2%, respectively).

In the 30 days after discharge, 218 (9.1%) patients experienced an ADE. With respect to the composite outcome, 862 participants visited the ED, were readmitted to hospital, or died in the 30 days after discharge (76.1%, 22.5%, and 1.4%, respectively). The incidence rate for the composite outcome was 1.51 events/100 person‐days.

With respect to ADEs, 120 (10.2%) patients prescribed at least one PIM continued from the community versus 98 (8.0%) not prescribed a community PIM experienced an ADE. For those prescribed a new PIM, 82 (10.9%) patients experienced an ADE compared to 136 (8.3%) patients who were not. In adjusted models, a prescription for at least one new PIM was associated with a 41% increase in the odds of ADE (OR, 95%: 1.41, 1.05-1.90). When the number of medications prescribed at discharge was modeled as a continuous variable, each additional community PIM and newly prescribed PIM was associated with a 10% (1.10, 1.01‐1.21) and 21% (1.21, 1.01‐1.45) increased odds of ADE, respectively.

With respect to the composite outcome, the incidence rate (per 100 person-days) for those prescribed at least one community PIM was higher versus none (1.67 vs. 1.36), respectively.  Similar results were found among those prescribed at least one new PIM versus none (1.64 vs. 1.45 events/100 person‐days). After adjustment, the prescription of at least one new PIM was associated with a 22% increase in risk (HR, 95%CI: 1.22; 1.00-1.49). When the number of medications prescribed at discharge was modeled as a continuous variable, each additional community PIM and newly prescribed PIM was associated with a 5% (1.05, 1.00-1.10) and 13% (1.13, 1.03-1.26) increased risk, respectively.

Medicine patients were more commonly continued on community PIMs than surgery patients (53% vs. 44%); for new PIMs, the respective values were 27% and 37% when comparing patients from medicine to surgical patients. The impact of PIMs on ED visits, re-hospitalization, and death in 30 days was similar between medical and surgical patients.

Limitations of study:
The study authors were able to determine which medications were filled, however unable to determine compliance with therapy. Additionally, medications not covered under the provincial drug plan were excluded. This reduced the amount of eligible PIMs for analysis by 25%, thus potentially underestimating the impact of these medications. 

Geriatric Cardiology Perspective:

In this prospective cohort study of hospitalized patients, the majority of elderly adults were at risk of being prescribed an existing or new PIM at the time of discharge. Importantly, this work by Weir et al. describes for the first time the inherent risk of adverse drug events at 30 days' time with prescriptions for new medications.4 Additionally, this risk of all-cause and ADE was higher when new medications were added compared to continuing community PIMs. The authors aptly note that medications considered an institutional standard of practice (such as anxiolytics and gastric acid reducing therapy) may be inadvertently prescribed at the time of discharge, and likely explains the higher rates of benzodiazepines and proton pump inhibitors prescribed in this study.5

This is of particular concern from a cardiac standpoint given age-related changes in renal function, hepatic metabolism, changes in body composition (increased body fat, and reduced muscle mass and total body water) which may affect the distribution, metabolism, and elimination of cardiovascular and noncardiovascular therapies.6 For example, in a study of elderly (median age 72 years) patients hospitalized with heart failure (HF), rehospitalization for HF was significantly higher among those on benzodiazepine therapy.7 Compounding this modifiable risk factor is the risk of polypharmacy – the median number of medications prescribed at the time of discharge in this study was eight. The use of more than five medications was most often seen in elderly HF patients (age >70 years) who also had difficulty performing routine daily activities and thus may unnecessarily expose individuals to risk of adverse outcomes.8

Certainly, available evidence has shown that antihypertensive agents, statins, antiplatelet and anticoagulants, β-adrenergic blockers, angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, and aldosterone antagonists benefit elderly patients with cardiovascular disease.9 However, this must be balanced with an understanding of age-related changes in end-organ responsiveness. A framework for the assessment and process of deprescribing has previously been described.10 As such, prioritizing drug discontinuation is a collaborative responsibility in the care of the elderly to reduce polypharmacy and improve health outcomes and quality of life measures. Aptly noted by Krishnaswami et al., "the continuum of good prescribing practices includes the deprescribing process."11

References

  1. OʼMahony D, OʼSullivan D, Byrne S, OʼConnor MN, Ryan C, Gallagher P. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing 2015;44:213‐8.
  2. By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2015;63:2227‐46.
  3. Choosing Wisely Canada (choosingwiselycanada website).2018. Available at:  https://choosingwiselycanada.org/recommendations/. Accessed 07/01/2020.
  4. Weir DL, Lee TC, McDonald EG, et al. Both new and chronic potentially inappropriate medications continued at hospital discharge are associated with increased risk of adverse events. J Am Geriatr Soc 2020;68:1184-92.
  5. Lee TC, Desforges P, Murray J, Saleh RR, McDonald EG. Off-label use of quetiapine in medical inpatients and post-discharge. JAMA Intern Med 2016;176:1390-1.
  6. Damluji AA, Forman DE, van Diepen S, et al. Older adults in the cardiac intensive care unit: factoring geriatric syndromes in the management, prognosis, and process of care: a scientific statement from the American Heart Association. Circulation 2020;141:e6-e32.
  7. Sato Y, Yoshihisa A, Hotsuki Y, et al. Associations of benzodiazepine with adverse prognosis in heart failure patients with insomnia. J Am Heart Assoc 2020;9:e013982.
  8. Goyal P, Bryan J, Kneifati-Hayek J, et al. Association between functional impairment and medication burden in adults with heart failure. J Am Geriatr Soc 2019;67:284-91.
  9. Fleg JL, Aronow WS, Frishman WH. Cardiovascular drug therapy in the elderly: benefits and challenges. Nat Rev Cardiol 2011;8:13-28.
  10. Scott IA, Hilmer SN, Reeve E, et al. Reducing inappropriate polypharmacy: the process of deprescribing. JAMA Intern Med 2015;175:827-34.
  11. Krishnaswami A, Steinman MA, Goyal P, et al. Deprescribing in older adults with cardiovascular disease. J Am Coll Cardiol 2019;73:2584-95.

Clinical Topics: Arrhythmias and Clinical EP, Geriatric Cardiology, Novel Agents

Keywords: Geriatrics, Patient Discharge, Anti-Anxiety Agents, Benzodiazepines, Analgesics, Opioid, Medication Reconciliation, Logistic Models, Antipsychotic Agents, Proton Pump Inhibitors, Cyclooxygenase 2 Inhibitors, Prevalence, Proportional Hazards Models, Thoracic Surgery


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