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QIPP
Agenda
Gastrointestinal
Outcomes of a medication optimisation review in
patients taking proton pump inhibitors
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Benckiser Healthcare Ltd supported the Polypharmacy Medicine Optimisation Review and the
lead author with a medical education grant and funded medical writing of the article. Reckitt
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accuracy of the article.
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©MGP 2015
Date of preparation: January 2015
POLYPHARMACY MEDICINE OPTIMISATION REVIEW
Outcomes of a medication
optimisation review in
patients taking proton pump
inhibitors
Diane McGinn,* Medicines Management Consultant, Preston, Lancashire, UK
Chris Roberts, CCG Practice Pharmacist, Mountview, Broadway and Belle Vue Practices, Fleetwood, Lancashire, UK
*Corresponding author: Diane McGinn, 5 Moss Bridge Park, Preston, Lancashire, PR5 5LZ, UK
Phone: +44 (0)7906 238392; Email: [email protected]
Introduction
Table 1: Baseline audit
P
roton pump inhibitors (PPIs) are one of the most
commonly prescribed groups of drugs.1–4 Although PPIs
are generally well tolerated, long-term use has been associated
with adverse effects such as increased risk of bone fracture, 5–8
nutrient deficiency,9–11 Clostridium difficile infection,12–15 and
pneumonia.16–18 Because of these risks, the lowest effective dose
of PPI should be used.19-21
NICE recommends that patients taking PPIs receive regular
reviews and should be encouraged to step down or step off their
treatment. 20,21 Despite this advice, PPI prescribing has continued
to increase, for example, in 2011–2012 omeprazole use increased
by 10.7% in the community setting in England, with a total of
25.8 million prescriptions in 2012. 22 It is possible that the NICE
guideline is not being followed and/or patients are finding it
difficult to maintain step down/off.
PPI patients
Practice 1
N=12,494
Practice 2
N=10,660
Practice 3
N=1729
Total
N=24,883
n (%)
1409 (11)
533 (5)
96 (6)
2038 (8)
Age, mean
(SD), years
55 (15)
62 (15)
55 (14)
60 (15)
Sex, % female
55
64
47
57
Number of
medications
taken, mean
(SD)
8 (4)
6 (4)
7 (4)
7 (15)
Not on other
medications,
n (%)
59 (4)
57 (11)
9 (9)
125 (6)
Without coded
indication for
PPI, n (%)
754 (54)
176 (33)
38 (40)
968 (47)
On 4 or more
medications,
n (%)
1180 (84)
357 (67)
78 (81)
1615 (79)
On 10 or more
medications,
n (%)
591 (42)
75 (14)
30 (31)
696 (34)
Attending
chronic disease
management
clinics, n (%)
803 (57)
246 (46)
59 (61)
1108 (54)
Proton pump inhibitors may trigger the very symptoms
that they are designed to treat because of compensatory
mechanisms.23,24 Studies have shown that patients can suffer
from rebound gastric acid hypersecretion following PPI
withdrawal, 25–27 which may make it difficult to maintain step
down/off.28 In our experience, many healthcare professionals
(HCPs) and patients are unaware of the risk of rebound
symptoms and how best to manage them. Alginates are a
suitable treatment for rebound as they suppress reflux
mechanically29 rather than suppressing acid production, and
can be used as an add-on to PPIs. 30 Gradual PPI reduction and
short-term alginate therapy may help patients to achieve and
maintain step off. 20,21,31
be a reason why PPIs are not a high priority in polypharmacy
patients’ medication reviews.
Although PPI use is increasing, the availability of generic PPIs
means that overall costs have not changed much;22 this may
As part of the Quality, Innovation, Productivity and Prevention
(QIPP) agenda, our group of practices reviewed the use of
PPI=proton pump inhibitor; SD=standard deviation.
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POLYPHARMACY MEDICINE OPTIMISATION REVIEW
Box 1: Patient exclusion criteria for the PMOR
››
››
››
››
››
Figure 1: PMOR and audits
Aged <18 years (except for GP review)
Under review at GI clinic or awaiting referral
Baseline audit
Awaiting gastroscopy or review
In end-stage care (GSF)
Patients receiving the following treatments:
▬▬ healing doses of PPIs <1 month for non-investigated dyspepsia
▬▬ maintenance doses of PPIs <1 month for non-ulcer dyspepsia
▬▬ healing doses of PPIs <2 months for gastro-oesophageal reflux
PMOR
disease/peptic ulcer disease
4 months
▬▬ Helicobacter pylori eradication therapy
▬▬ high-dose steroids with life-threatening or chronic illness,
e.g. patients awaiting transplant, post-transplant patients
▬▬ immunosuppression therapy
▬▬ chemotherapy or radiotherapy
›› Patients with the following conditions:
▬▬ Zollinger–Ellison syndrome
▬▬ grade 3 or 4 oesophagitis
▬▬ oesophageal strictures or oesophageal dilation
▬▬ history of oesophageal varices
▬▬ any of the following alarm signs:
yy anaemia
yy vomiting
yy weight loss
yy dysphagia
yy epigastric mass
yy haematemesis
yy jaundice
yy progressively worsening symptoms
Registered at a
chronic disease
management
clinic?
Yes
Due an appointment?
No
No
Reviewed by
practice
pharmacist* or GP†
Reviewed by
gastroenterology
nurse
Yes
Reviewed
by practice
nurse during
appointment
Post-PMOR audit
12 months
Follow-up audit
*Also reviewed by practice pharmacist if on ≥10 medications.
†
Reviewed by GP during ad hoc GP appointments.
GI=gastrointestinal; GSF=Gold Standards Framework; PMOR=Polypharmacy
Medicine Optimisation Review; PPI=proton pump inhibitor.
PMOR=Polypharmacy Medicine Optimisation Review.
non-steroidal anti-inflammatory drugs (NSAIDs). We also
took this opportunity to review PPI use as it was predicted
that many patients on PPIs would be taking other medications
and therefore would benefit from a medication review. Those
on four or more medications require an annual review, so
many of these patients may attend nurse-led chronic disease
management clinics. We considered whether routine visits,
such as appointments at chronic disease clinics, could offer an
ideal opportunity to review medication use, including PPIs. To
address this question, we conducted a Polypharmacy Medicine
Optimisation Review (PMOR). 32,33 To assess the effectiveness
of the PMOR, we conducted audits before and directly after the
PMOR and a follow-up audit 12 months later.
medications, and approximately half were attending chronic
disease clinics (see Table 1, p.2). These findings confirmed
that many patients may benefit from medication optimisation,
and that chronic disease clinics may be an ideal setting for
medication reviews.
Polypharmacy Medicine Optimisation Review
The PMOR was held from April to July 2012. Patients receiving
repeat PPI prescriptions were eligible for review unless they
met any exclusion criteria (see Box 1, above). Patients were seen
by a practice nurse, external gastroenterology nurse specialist,
practice pharmacist, or GP, who had attended an educational
session on the aims/methods of the PMOR (see Figure 1,
above). They were also seen by a GP if they experienced severe
symptoms after PPI step down/off.
Methods
The review process involved several steps. Patients were assessed
for their eligibility for step down/off (criteria outlined in
Figure 2, see p.4). Those eligible for step down were prescribed a
lower dose generic PPI, and those already on a low-dose PPI and
eligible for step off had their PPI prescription stopped. Patients
who stepped down/off PPIs were given a leaflet on lifestyle
advice (e.g. weight loss, diet) and a short-term supply of alginate
to help manage rebound symptoms.
The PMOR was conducted at Fleetwood Clinical Commissioning
Group (CCG), which comprises three general practices in
Fleetwood, Lancashire (now part of the Fylde and Wyre CCG).
Baseline audit
Prior to the PMOR, a baseline audit (in December 2011)
showed that PPI patients were taking an average of seven
3
POLYPHARMACY MEDICINE OPTIMISATION REVIEW
Figure 2: Eligibility criteria for PPI step down/off
All reviewed patients were offered the opportunity to complete a
patient satisfaction questionnaire to rate their experience of the
PMOR.
Is the patient ‘high risk?
Criteria for high risk:
• taking long-term high-dose NSAID
• taking other medications that are harmful to the gastric and duodenal lining
• previous ulceration
Yes
Medication prescribing and step down/off were assessed in an
audit after the PMOR (post-PMOR audit) and a follow-up audit
12 months after the end of the PMOR. GP referrals to secondary
care for gastrointestinal investigations were also analysed at
the follow-up audit. In addition, change in PPI prescribing was
assessed, based on Specific Therapeutic group Age-sex Related
Prescribing Units (STAR-PUs).
No
Not eligible
for PPI step
down or
step off
Is the patient taking a co-prescribed medication
that requires gastroprotection with a PPI?
Yes
If the co-prescribed medication
cannot be stopped, step
down to the lowest effective
dose of generic PPI
No
Results
Baseline audit
Of the 24,883 patients registered in the three practices, 2038 were
taking PPIs (see Table 1, p.2). Most (79%) patients using PPIs were
taking four or more medications and 54% were attending chronic
disease clinics. The most frequently prescribed drugs potentially
requiring gastroprotection or causing gastrointestinal symptoms
were NSAIDs (12%) and selective serotonin reuptake inhibitors
(SSRIs) (17%) (not shown).
Does the patient meet the following criteria?
history of peptic ulceration associated
with H. pylori-negative status
• Barrett’s oesophagus
•
Yes
No
Eligible for PPI
step down only
Eligible for PPI step
down or step off
Polypharmacy Medicine Optimisation Review
A total of 773 patients using PPIs underwent the PMOR (see
Figure 3, below). At the initial review, 167/773 (22%) patients
stepped down and 95/773 (12%) stepped off their PPI. Overall,
NSAID=non-steroidal anti-inflammatory drug; PPI=proton pump inhibitor.
Figure 3: Proton pump inhibitor step downs/step offs
Patients seen during PMOR (773)
Seen by
Pharmacist 145 (19%)
Gastroenterology nurse
236 (31%)
GP—ad hoc
48 (6%)
Practice nurse—chronic
disease clinics
344 (45%)
Step down
56 (39%)
Step off
47 (32%)
Step down
102 (43%)
Step off
28 (12%)
Step down
6 (13%)
Step off
12 (25%)
Step down
3 (1%)
Step off
8 (2%)
Maintenance at post-PMOR audit
39 (70%)
34 (72%)
86 (84%)
20 (71%)
4 (67%)
9 (75%)
3 (100%)
5 (63%)
Maintenance at follow-up audit
(12 months after the end of the PMOR)
27 (48%)
29 (62%)
77 (75%)
16 (57%)
4 (67%)
6 (50%)
2 (67%)
2 (25%)
4 (3%)
11 (8%)
1 (0%)
6 (3%)
1 (2%)
1 (2%)
4 (1%)
6 (2%)
31 (21%)
40 (28%)
78 (33%)
22 (9%)
5 (10%)
7 (15%)
6 (2%)
8 (2%)
At initial review
Additional step downs/offs
after initial review, which were
maintained at follow-up audit
Final numbers at follow-up audit
PMOR=Polypharmacy Medicine Optimisation Review.
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POLYPHARMACY MEDICINE OPTIMISATION REVIEW
Figure 4: Patient satisfaction questionnaire on the PMOR
4.9
Were your privacy and dignity respected?
4.8
Overall, how would you rate your satisfaction
with the medicines review you received?
4.7
What is your opinion of the patient information
leaflets that you received for your service?
4.9
Did you feel that your questions were well answered
and that you were given appropriate advice?
4.9
Did you feel that the nurse/pharmacist/
doctor listened to what you had to say
and took your concerns seriously?
4.5
If your medication was changed, how
happy were you about this?
4.9
Did you feel that the review of your medicine
was properly explained to you?
0
1
2
3
4
5
6
Mean score (maximum possible score=5)
A total of 110 patients (14%) completed the patient satisfaction questionnaire; each question was answered with a score
of 1–5 where 1 is the worst outcome and 5 is the best outcome. Error bars represent standard deviations.
PMOR=Polypharmacy Medicine Optimisation Review.
during the 4-month review period, 329 medication prescriptions
(including PPIs) were stopped.
The follow-up audit showed reductions in NSAID and SSRI
use, as well as PPI use (not shown). Out of a total of 102
patients on NSAIDs, 15 (15%) reduced their dose and 64
(63%) stopped their NSAID altogether. Of the 123 patients
on SSRIs, nine (7%) and seven (6%) had their SSRI reduced
or stopped, respectively. The total prescribing cost savings
resulting from the PMOR was £7707 per annum (excluding
the cost of reviews).
Post-PMOR audit
At the end of the PMOR, maintenance of PPI step down/off was
high (132/167 [79%] and 68/95 [72%], respectively; see Figure 3,
p.4). In addition, four patients (4/773 [1%]) stepped down and 12
patients (12/773 [2%]) stepped off PPIs who had not done so at the
initial review.
Comparison of gastrointestinal clinic referrals and endoscopies
in the 12 months preceding and following the PMOR showed
a substantial decrease for the combined practices (see Table 2,
p.6). Of note, endoscopies decreased by 82% for the three
practices combined, whereas a decrease of only 8% was observed
for the remaining practices combined in the Fylde and Wyre
CCG.
Patients rated the PMOR highly in the patient satisfaction
questionnaire, with a mean score of 4.8 (out of 5) for their
satisfaction with the medication review (see Figure 4, above).
Patients’ comments were extremely positive and highlighted that
they welcomed the opportunity to have a face-to-face discussion.
Follow-up audit
Most patients who stepped down/off PPIs at the initial review
maintained their change at the follow-up audit 12 months after
the end of the PMOR (110/167 [66%] for step down and 53/95
[56%] for step off) (see Figure 3, p.4). In addition, six patients
(6/773 [1%]) stepped down and 12 patients (12/773 [2%])
stepped off PPIs since the post-PMOR audit. In total, 120/773
(16%) of the reviewed patients stepped down and 77/773 (10%)
stepped off PPIs.
Proton pump inhibitor prescriptions/STAR-PU decreased in
two of the PMOR practices during the PMOR (see Table 3, p.6).
For the three practices together, there was a 2.05% decrease and
for the other practices in the CCG, there was a 1.79% increase.
Proton pump inhibitor prescriptions/STAR-PU increased
during/following the PMOR, but quarter on quarter percentage
changes were lower for the PMOR practices than the other CCG
practices for six of the eight quarters examined.
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POLYPHARMACY MEDICINE OPTIMISATION REVIEW
Table 3: Proton pump inhibitor prescribing
Table 2: GI referrals before and after the PMOR
Practice 1
Practice 2
Practice 3
PMOR
practices
combined
Other
practices
in CCG
combined*
24,158
124,804
Time period
Before PMOR
Total number
of registered
patients,
Jul 2012
12,264
10,187
1707
Practice 1 Practice 2 Practice 3 Mean
change
for PMOR
practices
Mean
change
for other
practices
in CCG
–
–
Before PMOR
All GI referrals 81
2011–2012
73
19
173
1006
Upper GI
referrals
2011–2012
29
31
8
68
492
Upper GI
endoscopy
2011–2012
16
26
8
50
262
Jan–Mar 2012
–
–
–
During PMOR
Apr–Jun 2012
1.04%
–2.08%
–5.11%
–2.05%
1.79%
4.32%
0.61%
–5.11%
–0.06%
0.80%
Oct–Dec 2012
4.57%
5.89%
6.12%
5.52%
1.92%
Jan–Mar 2013
–2.31%
4.59%
–1.51%
0.26%
–5.12%
Apr–Jun 2013
5.85%
0.34%
3.48%
3.23%
3.50%
Jul–Sep 2013
1.39%
1.78%
–0.34%
0.94%
2.18%
Oct–Dec 2013
–10.63%
–11.38%
8.61%
–4.47%
2.53%
Jan–Mar 2014
–2.52%
–7.06%
–5.59%
–5.06%
–4.71%
During/after PMOR
Jul–Sep 2012
After PMOR
Total number
of registered
patients,
Jul 2013
Quarter on quarter percentage change in
PPI prescribing/STAR-PU
After PMOR
12,030
All GI referrals 27 (–67%)
2012–2013 (%
change from
2011–2012)
Upper GI
referrals
2012–2013 (%
change from
2011–2012)
5 (–83%)
Upper GI
endoscopy
2012–2013 (%
change from
2011–2012)
2 (–88%)
10,110
14 (–81%)
1676
16 (–16%)
10 (–68%) 9 (+13%)
2 (–92%)
5 (–38%)
23,816
57 (–67%)
24 (–65%)
9 (–82%)
124,447
995 (–1%)
CCG=Clinical Commissioning Group; PMOR=Polypharmacy Medicine
Optimisation Review; PPI=proton pump inhibitor; STAR-PU=Specific Therapeutic
group Age-sex Related Prescribing Unit.
456 (–7%)
In contrast with previous interventions to manage PPI use, 34–40
the PMOR led to reduced use of several drug classes, not only
PPIs. Of note was the reduction in NSAIDs (15% stepped
down and 63% stepped off); one of the main indications for
PPIs is gastroprotection for high-risk NSAID users,4,41,42 so the
reduction in NSAID use was likely to have contributed to the
reduction in PPI use. Furthermore, the overuse of NSAIDs is
a recognised problem in itself 43,44 so the PMOR has helped to
address the inappropriate prescribing of both PPIs and NSAIDs.
The prescribing cost savings were £7707 per annum (excluding
the cost of reviews), but if the PMOR is applied to all eligible PPI
patients in the CCG (151,597 registered patients in July 2012),
an estimated total of £46,951 could be saved per annum.
240 (–8%)
*Data are from 17 of the 18 remaining practices in the Fylde and Wyre CCG; data
could not be obtained from one practice due to coding changes.
CCG=Clinical Commissioning Group; GI=gastrointestinal; PMOR=Polypharmacy
Medicine Optimisation Review.
Discussion
Summary
The PMOR approach was very effective at helping patients to
step down/off PPIs and sustain these changes over time. The
questionnaire (see Figure 4, p.5) confirmed that most patients
were much more willing to change or stop their medication(s)
than anticipated.
Although PPI step down/off was successful, the STAR-PU
data show that overall PPI prescribing increased over the year
following the PMOR (see Table 3, above right). This suggests
that additional patients were started on PPIs, which would be
appropriate as long as the prescription was for a clear indication.
In a separate audit, we found that at least 480 aspirin users were
started on PPIs for gastroprotection, which may be a reason for
the increased PPI prescribing. It should be noted that STAR-PU
does not take into account the duration of each prescription or
whether the prescriptions were repeat or acute.
Most patients managed to maintain their change in PPI use for
at least 12 months (66% for step down and 56% for step off).
During this period, an average of 2.9 bottles (standard deviation
3.6) of alginate were used per patient stepped down/off. This
indicates that alginates were used as a short-term therapy only,
confirming that there was a true reduction in medication use
rather than a switch from one drug to another.
An unexpected observation was the decrease in gastrointestinal
referrals (67% decrease) and upper gastrointestinal endoscopies
(82% decrease) following the PMOR (see Table 2, above left).
6
POLYPHARMACY MEDICINE OPTIMISATION REVIEW
Key points
Potential reasons for this include reduced NSAID use,
increased/optimised PPI use in at-risk patients, and educational
sessions for HCPs helping to improve patient care, and so
reducing the need for referrals. However, further research is
needed to determine whether the reduction was due to the
PMOR. If indeed the PMOR did have an impact on referrals and
endoscopies, its implementation could lead to significant cost
savings (estimated saving of £145,618 for referrals and £90,864
for endoscopies for the CCG per annum).
›› NICE recommends that patients taking proton
pump inhibitors (PPIs) are reviewed regularly and
encouraged to step down/off their PPI due to the risk
of adverse effects
›› However, PPI withdrawal is often difficult to maintain
because of rebound acid hypersecretion, and PPI
prescribing has continued to increase
›› We aimed to improve the implementation of the
NICE guideline on dyspepsia and optimise PPI use by
reviewing patients who were being prescribed PPIs
›› The medication review was found to be highly
effective at helping patients to step down/off their
PPI and other medications—there was also a 67%
reduction in gastrointestinal clinic referrals and an
82% reduction in endoscopies
›› Use of this review process on a wider scale is likely
to result in considerable cost savings and reduce the
incidence of medication-related adverse effects.
Strengths and limitations
This PMOR was conducted in a ‘real world’ setting,
demonstrating its feasibility and relevance to current clinical
practice. However, only three practices from one CCG were
included, so the HCPs and patients may not be representative
of other CCGs. Also, behaviour of HCPs may have been
influenced by the knowledge that they were taking part in a
new programme. Another limitation is that the estimated cost
savings may be subject to bias as they did not take into account
the inter-practice variability in results or the costs involved in
running the PMOR.
Comparison with existing literature
The results of the PMOR and the patient satisfaction
questionnaire are reflective of a previous interview-based study
in the UK, which showed that patients are generally agreeable
to changes to their PPI prescription, contrary to what many
GPs had assumed.45 Other UK studies have had mixed success;
an educational intervention (results of a PPI audit, along with
the NICE guideline on dyspepsia 21) did not have any effect
on PPI use,1 whereas two nurse-led programmes were very
effective at reducing PPI use. 36,40 In both nurse-led studies,
participants were offered an alginate to help manage their
symptoms.
of the PMOR supports the widespread use of this strategy
(or similar) for the effective optimisation of PPIs, NSAIDs,
and other medications. The PMOR approach is expected to
result in considerable cost savings, to reduce the occurrence of
medication-associated adverse effects and, as we observed, may
also reduce the use of secondary healthcare services. Although
our PMOR focused on PPI patients, a similar strategy could be
applied to other patient groups who may benefit from reducing
their medication use.
Acknowledgements
The authors would like to thank all the patients who were
involved in the Polypharmacy Medicine Optimisation Review
and Elements Communications Ltd (Westerham, Kent, UK) for
medical writing services.
Implications for research and/or practice
The findings of the PMOR and previous studies indicate that
HCP–patient discussions are vital for effective medication
optimisation. Patients should be made aware of the risk of
rebound acid hypersecretion, 23,24 counselled on how to selfmanage rebound symptoms, and reassured that these symptoms
should only occur in the short-term as a consequence of PPI
withdrawal.
Source of funding
The Polypharmacy Medicine Optimisation Review was
supported by a medical education grant from Reckitt Benckiser
Healthcare Ltd (Slough, Berkshire, UK). Medical writing
assistance for this manuscript was also funded by Reckitt
Benckiser Healthcare Ltd.
Although patients can be encouraged to reduce PPI use,
educating HCPs is key to avoiding inappropriate prescribing
in the first place. Studies suggest that PPIs are often prescribed
without a clear indication or for an unlicensed indication,4,42,46,47
so there is a need to improve HCP awareness of the risks
associated with PPIs.2,3,19,48
Conflicts of interest
DM received a medical education grant from Reckitt Benckiser
Healthcare Ltd to conduct the Polypharmacy Medicine
Optimisation Review. CR has no competing interests to
disclose.
Overall, our preliminary trial of the PMOR has delivered
very promising results with important implications for future
clinical practice. Our project was selected by NICE as one
of the top 20 solutions to improve medicines and patients’
lives,49 reflecting the clinical value of our findings. The success
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