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QIPP Agenda Gastrointestinal Outcomes of a medication optimisation review in patients taking proton pump inhibitors Production of this supplement has been funded by Reckitt Benckiser Healthcare Ltd. Reckitt 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 Benckiser Healthcare Ltd has had the opportunity to comment on the medical content and accuracy of the article. The content of this supplement was produced independently of MGP Ltd and of Guidelines in Practice. The views and opinions of the author are not necessarily those of Reckitt Benckiser Healthcare Ltd, or of Guidelines in Practice, its publisher, advisers, or advertisers. No part of this publication may be reproduced in any form without the permission of MGP Ltd and Reckitt Benckiser Healthcare Ltd. ©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. 2 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. 4 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. 5 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. 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