Problems Associated with Deprescribing of Proton Pump Inhibitors
Abstract
:1. Introduction and Gastric Acid Regulation
2. Safety of Long-Term PPI Use
3. Definition of PPI Deprescribing
4. Rebound Acid Hypersecretion
5. PPI Desprescriping Trials
6. Deprescribing Guidelines
7. Large Gap in the Knowledge of What Should Be Recommended
8. Conclusions
Funding
Conflicts of Interest
References
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The Steps of PPI Deprescribing | |
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Step 1 | Review indication and effectiveness |
Step 2 | Assess the balance of benefits and harms |
Step 3 | Assess patients values and preferences |
Step 4 | Decide wether to continue, reduce dose or discontinue PPI therapy |
Step 5 | Deprescribe and monitor |
Step-Down Studies | |||
Authors: Helgadottir et al. (2017) [69] | Participants: GERD patients with EE (n = 50) | Deprescribing method: Step-down dose by half vs. continuous same-dose treatment | Outcome: Step-down was successful in 76% |
Methods: A double-blind randomized trial Country: Iceland | PPI duration: > 2 years PPI dose: 40 or 20 mg Age: median 59 years Gender (F/M): 25/25 | Setting: Hospital Follow-up time: 8 weeks | Comment: Female gender was an independent predictor for a successful step-down |
Authors: Inadomi et al. (2003) [57] | Participants: Heartburn patients (n = 117) | Deprescribing method: Step-down from multiple- to single-dose | Outcome: Step-down was successful in 79.5% |
Methods: A non-controlled prospective study Country: USA | PPI duration: > 8 weeks PPI dose: > 20 mg Age: median 66 years Gender (F/M): 5/112 | Setting: VA hospital and outpatient clinic Follow-up time: 6 months | Comment: Longer PPI duration before step-down was an independent predictor of PPI requirement |
Discontinuing Studies | |||
Authors: van der Velden et al. (2010) [47] | Participants: GERD patients on long-term PPI therapy (n = 141) | Deprescribing method: Abrupt discontinuation with 20 mg PPI as escape medication vs. daily 20 mg PPI with placebo escape medication | Outcome: 32% persisted daily PPI dosage, 43% reduced their dosage, 25% used less than 2 tablets/week. |
Methods: A double-blind, parallel-group trial Country: The Netherlands | PPI duration: > 6 months PPI dose: 20 mg Age: mean 57 years Gender ratio: 56% | Setting: Primary care Follow-up time: 13 weeks | Comment: About 20% of long-term PPI users became satisfied on placebo with hardly any PPIs (0.7 tab-let/week) |
Authors: Zwisler et al. (2015) [73] | Participants: Long-term PPI users without history of esophagitis, ulceration or current NSAIDs use. (n = 85) | Deprescribing method: Abrupt discontinuation vs. continuous treatment | Outcome: Discontinuation was successful in 27% of patients |
Methods: A double-blinded randomised placebo-controlled trial Country: Denmark | PPI duration: > 8 weeks PPI dose: 40 mg Age: median 59 years Gender (F/M): 48/37 | Setting: Primary care Follow-up time: 1 year | Comment: Significantly more men had an unsuccessful discontinuation |
Authors: Björnsson et al. (2006) [11] | Participants: Long-term PPI users without PUD or EE (n = 96) | Deprescribing method: Discontinuation: abrupt vs. 3 weeks tapering | Outcome: Discontinuation was successful in 27% (31% of tapering and 22% of abrupt discontinuation, NS) |
Methods: A double-blind, placebo-controlled trial Country: Sweden | PPI duration: > 8 weeks PPI dose: 20 mg Age: median 63 years Gender (F/M): 52/44 | Setting: Hospital Follow-up time: 1 year | Comment: GERD and serum gastrin were independent predictors of PPI requirement |
Authors: Pilotto et al. (2003) [46] | Participants: Erosive esophagitis patients (n = 56) | Deprescribing method: Abrupt discontinuation vs. continuous treatment | Outcome: 62.5% had a relapse of erosive esophagitis 6-months after discontinuation |
Methods: A prospective, randomized, double-blind study Country: Italy | PPI duration: 6 months PPI dose: 20 mg Age: > 65 years of ageGender (F/M): Not given for the double-blind phase | Setting: Hospital Follow-up time: 1 year | Comment: 81% healing rate was in the maintenance phase after 4-months of 20 mg following a step-down from 40 mg for 8 weeks. |
On-Demand Studies | |||
Authors: Bayerdorffer et al. (2016) [66] | Participants: Symptomatic NERD patients (n = 301) | Deprescribing method: On-demand vs. continuous treatment | Outcome: On-demand was successful for 92% |
Methods: A multicenter, open-label, randomized, parallel-group study Country: Austria, France, Germany, South Africa and Spain | PPI duration: 4 weeks PPI dose: 20 mg Age: mean 48 years Gender (F/M): 179/122 | Setting: Hospital Follow-up time: 6 months | Comment: On-demand treatment was non-inferior to continuous treatment |
Authors: Bour et al. (2005) [67] | Participants: Non-severe GERD patients with frequent symptom relapses (n = 71) | Deprescribing method: On-demand vs. continuous treatment | Outcome: On-demand was successful, with a high symptom relief in 74.6% |
Methods: A randomized, open-label study Country: France | PPI duration: > 1 year PPI dose: 10 mg Age: average 50 years Gender ratio: 58% men | Setting: Hospital Follow-up time: 6 months | Comment: There was a significant decrease in medication consumption in the on-demand group |
Authors: Janssen et al. (2005) [68] | Participants: GERD patients (n = 215) | Deprescribing method: On-demand vs. continuous treatment | Outcome: On-demand was successful in 69.3% |
Methods: A multicentre, open-label Country: Germany, France, Switzerland and Hungary. | PPI duration: 4 weeks PPI dose: 20 mg Age: mean 50 years Gender (F/M): 115/100 | Setting: Did not describe the clinical settings or type of centers Follow-up time: 6 months | Comment: Patients were satisfied with the on-demand therapy which was non-inferior to continuous therapy with regard to symptom control |
Indications for Continuous PPI Therapy |
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Severe esophagitis (LA grade C or D) Barrets esophagus |
Documented history of bleeding GI ulcer |
Chronic NSAIDs use with bleeding risk factors |
Zollinger-Ellison syndrome |
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Helgadottir, H.; Bjornsson, E.S. Problems Associated with Deprescribing of Proton Pump Inhibitors. Int. J. Mol. Sci. 2019, 20, 5469. https://doi.org/10.3390/ijms20215469
Helgadottir H, Bjornsson ES. Problems Associated with Deprescribing of Proton Pump Inhibitors. International Journal of Molecular Sciences. 2019; 20(21):5469. https://doi.org/10.3390/ijms20215469
Chicago/Turabian StyleHelgadottir, Holmfridur, and Einar S. Bjornsson. 2019. "Problems Associated with Deprescribing of Proton Pump Inhibitors" International Journal of Molecular Sciences 20, no. 21: 5469. https://doi.org/10.3390/ijms20215469