Discussion
In this study, we deep-dived into the medicine changes that were
implemented during the medication review intervention leading to
improved HRQoL and reduced mortality.3 The results in
Table 1 show that even though there were three times the number of
discontinuations (26% vs 8.7%) in the medication review group, the
persistence of the discontinuations after 4 and 13 months were similar
between groups (medication review: 91% at 4 months and 82% at 13
months; usual care: 83% at 4 months and 86% at 13 months). The high
persistence in the medication review group despite the larger number of
changes could be due to improved cross-sectoral communication as the
patient’s general practitioner (GP) was involved before implementation
of the changes and notified of the changes after implementation.
While the overall persistence of changes was high, some medicines were
more prone to rebound than others as evidenced in Table 4. Of note, even
the highest rebound rates were roughly 1/3 meaning that even for these
medicines, discontinuation attempts were successful for 2/3 of the
patients. The rebounded medicines were almost exclusively symptomatic
treatments where recurrence of symptoms could easily be identified and
therapy reinitiated, while the two preventive medicines with high
rebound rates both have easy monitoring options (bone mineral density
for alendronate and blood pressure for bendroflumethiazide).
Interestingly, discontinuation of opioids and benzodiazepines, which we
consider symptomatic treatments, were more often successful than the
opposite despite the added risk of withdrawal symptoms.
In Figure \ref{222994}, other patterns regarding discontinuation and rebounding are
apparent. For some medicine groups, the medication review results in
fast and lasting reductions compared with usual care, i.e. for proton
pump inhibitors (drugs for peptic ulcer and gastro-oesophagael reflux
disease), opioids, paracetamol/acetaminophen (other analgesics and
antipyretics), antithrombotic agents, antiepileptics, furosemide (high
ceiling diuretics), and potassium (which follows furosemide
prescriptions). For other medicines, the difference in discontinuations
is not persistent, suggesting that the same changes will happen in the
usual care group but over a longer time period, i.e. for drugs against
constipation, vitamin B12 and folic acid, blood glucose-lowering drugs
excl. insulins, statins (lipid modifying agents, plain), selective
calcium channel blockers with many cardiovascular effects, and hypnotics
and sedatives. For antidepressants and adrenergic inhalants, the
medication review discontinuations seem to be unsuccessful with
discontinuation of antidepressants being the least successful. Lastly,
the calcium supplement discontinuations are outnumbered by new
prescriptions leading to an overall and similar increase in
prescriptions in both groups.
The reasons for the discontinuations in the medication review group
listed in Table 2 clearly show that lack of indication is by far the
most common reason to discontinue. Note that only the primary reason is
listed, hence safety-related concerns may also apply when the primary
reason for discontinuation was lack of indication. Nonetheless, it is
evident that to reduce overprescription, a thorough review of the
patient’s medical history is needed to understand the (original)
indication for the patient’s treatments. In cases where the indication
is not obvious, the patient or the patient’s family or GP may have this
valuable information, further highlighting the need for a strong patient
involvement and cross-sectoral collaboration when conducting medication
reviews.
The results in Table 3 show that many of the medicines that were more
often discontinued in the medication review group than in the usual care
group are medicines which can negatively impact, especially older
patients’, HRQoL. For example, metoclopramide, citalopram, tramadol,
tiotroprium and zopiclone may commonly cause dizziness and other
important adverse effects. Even low dose aspirin may cause significant
bleeding15 and quinine may increase mortality risk in
heart failure patients.16 So, while a medication
review is a complex intervention, the changes to the medicine may very
well be one of the causes of the observed positive effects on HRQoL and
mortality.
Medication reviews are labor intensive as they require a comprehensive
evaluation of the patient’s medical history and prescriptions to
accurately evaluate their current medication use and indications.
Therefore, it is important to identify the patients that would benefit
most from medication reviews to optimize the allocation of health
resources. Table 5 lists the factors that were statistically
significantly associated with the number of overprescribed medicines for
this population. Only two factors were associated with fewer
overprescribed medicines; not being motivated for medicine changes or
being referred from the geriatric department. Patients who were not
motivated for medication changes had 26% fewer overprescribed medicines
at the first visit. It is unknown whether this is due to them having
fewer overprescribed medicines prescribed or an unwillingness to consent
to the proposed medicine changes. Still, even patients that were not
motivated for medicine changes had a median of 3 medicines discontinued
or reduced in dosage. Patients referred from the geriatric department
had 25% fewer overprescribed medicines, most likely due to some extent
of medication reviews being performed prior to referral. Multiple
factors were associated with an increased number of overprescribed
medicines. The number of medicines was an important factor with 8% more
overprescribed medicines per additional medicine prescribed at baseline.
This is similar to the finding by Steinman et al.17 and intuitively makes sense as more medicines impair overview while
offering more opportunities for mistakes. However, not only the number
of medicines but also the sedative and anticholinergic burden of the
medicines (as measured with the Drug Burden Index) impacted the number
of overprescribed medicines with 15%–26% (full model or univariate
model) more overprescribed medicines per one increase in Drug Burden
Index. Besides the patient characteristics, we also identified some
medicines that seem to be proxies for suboptimal medicine treatment.
Thus, a prescription of metoclopramide was associated with a 42%–73%
(full model or univariate model) increase in overprescribed medicines.
Thus, metoclopramide, non-steroid anti-inflammatory drugs (propionic
acid derivatives), and drugs for urinary frequency and incontinence are
all medicines that should serve as an alarm bell that may prompt
medication reviews in patients exposed to polypharmacy.
Strengths and limitations
The strength of this study is the completeness of data and long
follow-up of medicine changes due to medication reviews thatoverall resulted in improved clinical outcomes for the patients.
The main limitation is that we cannot correlate individual medicine
changes to these outcomes due to the design of the study. Also, all
analyses in this paper are post-hoc explorative studies that require
further confirmative studies.