Discussion
This post-hoc analysis of a randomised controlled trial (MedBridge) in
older patients identified multiple risk factors and protecting factors
for drug-related readmissions within 12 months after hospital discharge.
Sixteen risk factors related to age, previous hospital visits,
medication use, multimorbidity and cardiovascular, liver, lung and
peptic ulcer disease were identified. Protecting factors for
drug-related readmissions were previous dementia diagnosis, and urinary
tract infection and injuries, intoxications and other complications of
external factors as discharge diagnosis. Sixteen percent of the hospital
revisits assessed in this study were potentially preventable
drug-related revisits. The two most prevalent diseases and causes
related to preventable revisits were heart failure and COPD, and
inadequate treatment and insufficient or no follow-up, respectively.
The identified risk factors in this study confirm results of previous
studies showing that age, previous hospital visits, number of
medications and comorbidity were positively associated with drug-related
readmissions [1,3]. Although there is little agreement on specific
diseases that affect drug-related visits in the literature,
cardiovascular disease and its treatment are often reported as risk
factors for drug-related (re)admissions [1,3,4]. Previous liver
disease and peptic ulcer disease were the risk factors with the highest
HRs, but are not commonly identified risk factors in other studies.
Pharmacotherapy for management of severe liver disease and adjustment of
pharmacotherapy based on changes in pharmacokinetics and
pharmacodynamics due to liver disease are challenging for clinicians
[16,17]. Hence, it seems plausible that inappropriate
pharmacotherapy for patients with existing liver disease may cause
hospital admissions. A previous study by our research group at Uppsala
University Hospital, one of the current study sites, found that
medications prescribed for peptic ulcer or gastroesophageal reflux
disease were associated with an increased risk of readmission in older
patients [18]. Furthermore, medications that may cause
gastroduodenal bleeding (e.g., antiplatelets and anticoagulants) are
often identified as risk factors for drug-related readmissions [1,3]
and this risk may be higher in patients with previous peptic ulcer
disease. However, our results on previous liver and peptic ulcer disease
should be interpreted with caution, as the prevalence rates of these
diseases in medical histories were low (n=16, 0.6%, and n=37, 1.4%,
respectively) and no related revisits of patients with these diseases
were identified in our random sample of 400 participants. Lung disease
(mainly COPD) in the medical history and as discharge diagnosis were
risk factors in our study, confirming the results of our previous study
at Uppsala University Hospital showing that asthma and COPD were
associated with an increased risk of readmission [18].
Interestingly, previous dementia diagnosis was a protecting factor for
drug-related readmissions in our study, in contrast to other studies
that have identified cognitive impairment or dementia as risk factors
for drug-related (re)admissions [19,20]. A possible explanation may
be that dementia generally occurs in more complex patients and that
their readmissions may frequently be classified as ‘caused by
progression of the disease’ (i.e., unlikely to be drug-related), rather
than being caused by a DRP. This is supported by dementia not appearing
as a protecting factor for all-cause readmission in our secondary
analysis. The other protecting factors in our study (urinary tract
infections and injuries, intoxications and other external factors as
discharge diagnosis) may be explained by their relative unrelatedness to
pharmacotherapy, in contrast to other discharge diagnoses.
The prevalence of potentially preventable drug-related revisits in our
study (47% of all possibly drug-related visits and 16% of all
unplanned visits) confirms the average prevalence in recent systematic
reviews (43% of drug-related readmissions based on six studies [4]
and 15% of all-cause readmissions based on four studies [3]). The
diseases most often related to these preventable visits were
cardiovascular disease (mainly heart failure, 28%) and COPD (13%),
followed by gastrointestinal bleeding or ulcer (8.2%). These results
seem in line with the identified risk factors for drug-related
readmissions in this study. For both heart failure and COPD, inadequate
use of medications is associated with poor clinical outcomes and
exacerbations are often avoidable through better prescribing by
clinicians and clearer instructions for patients [21–24].
Gastroprotective proton pump inhibitor treatment is an evidence-based
strategy to prevent gastrointestinal bleeding or ulcers. However, recent
Swedish studies focusing on the potential harmful effects of long-term
proton pump inhibitor treatment may have led to the restrictive use of
gastroprotection in older patients [25–27].
The three main causes (inadequate treatment, insufficient or no
follow-up and non-compliance) that accounted for 78% of all preventable
revisits in our study indicate the potential for improvement through
better treatment guideline adherence and patient involvement and
education [28,29]. Further, 39% of the potentially preventable
drug-related revisits could have been prevented by the medication review
in the MedBridge trial, if the review had been performed optimally. A
previous process evaluation of the trial found a lack of integration of
medication reviews into the daily workflow at the ward, inadequate time
allotted for follow-up on treatment changes and no medication
reconciliation upon discharge by the pharmacist in more than half of the
patients [30]. Improving these shortcomings could make medication
review an effective strategy to prevent hospital revisits. However, our
results indicated that an estimated 6% reduction in hospital revisits
within 12 months (39% of the 16% potentially preventable drug-related
revisits) might be the maximum achievable by a hospital-based
pharmacotherapy intervention, making it challenging to conduct
adequately powered clinical trials.
This study has several strengths.
The large study population with
long and complete post-discharge follow-up and the use of a validated
method to identify drug-related revisits increase the reliability of the
results. There are also some limitations to the study. Only patients who
had been admitted to general internal medicine or internal medicine
subspecialty wards were included, which limits generalisability to a
broader group. We excluded one-day admissions, patients who had recently
undergone a medication review and patients receiving palliative
treatment, which may have led to the exclusion of patients with both
relatively mild and severe health conditions. All analyses and
assessments were based solely on electronic data from the regional
health registries and the hospitals’ general EHR systems, which could
lead to potential under- or overestimation of study outcomes. Cytostatic
treatment is often prescribed in a separate system that was not
accessible to the researchers. Hence, cancer was a risk factor for
all-cause readmissions in our study, but not drug-related readmissions.
Anticancer drugs have been associated with readmissions in previous
studies [1,3]. For risk factor analysis, we lacked data about
medications upon discharge, although we included the number of
medications upon admission. For the preventability assessment, we chose
not to include which medications were involved in each drug-related
visit, because of the generally complex pharmacotherapy and multiple
medications involved (e.g., inadequate heart failure treatment often
involves (the lack of) four different drug substances). We could have
reported all therapeutic drug classes that were potentially involved,
but the reliability of such results would have been questionable.
Conclusion
Risk factors for drug-related readmissions in older hospitalised
patients were age, previous hospital visits, multimorbidity, medication
use and cardiovascular, liver,
lung and peptic ulcer disease. Potentially preventable drug-related
hospital revisits are common and might be prevented through adequate
medication use and follow-up in older patients with cardiovascular or
lung disease. Interventions to reduce drug-related hospital visits are
generally conducted in older patients with multiple medications in use.
In addition, the study suggests focusing on patients with multiple
previous visits and those with heart failure or COPD. Hospital revisits
in these patients may be prevented through better treatment guideline
adherence concerning adequate pharmacotherapy and treatment follow-up,
and through better patient education and involvement.