Page 67 - IDF Journal 2023

EDUCATIONAL OFFERINGS
Structural and functional changes in the gastric mucosa
Enteric infections* SIBO
Clostridium difficile
infection
Box 2. Tips!
Acute kidney injury
PPls
Chronic kidney disease
Dementia
Gastrointestinal malignancies
Cardiovascular events, negative effect on clopidogrel‡
Pneumonia
REFERENCES
1 Fass R, Sifrim D. Management of heartburn not responding to proton pump inhibitors. Gut. 2009 Feb;58(2):295-309.
2 Maret-Ouda J, Wahlin K, El-Serag HB,
et al. Association Between Laparoscopic Antireflux Surgery and Recurrence of Gastroesophageal Reflux. JAMA. 2017 Sep 12;318(10):939-946
3 Attwood SE, Ell C, Galmiche JP, Fiocca
R, et al. Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: data from the SOPRAN and LOTUS studies. Aliment Pharmacol Ther. 2015 Jun;41(11):1162-74.
4 Wright MJ, Sullivan RR, Gaffney-Stomberg E, et al. Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: a randomized, crossover, controlled clinical trial. J Bone Miner Res. 2010 Oct;25(10):2205-11.
5 Khalili H, Huang ES, Jacobson BC, et al. Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study. BMJ. 2012 Jan 30;344:e372.
6 Gray SL, LaCroix AZ, Larson J, et al. Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women’s Health Initiative. Arch Intern Med. 2010 May 10;170(9):765-71.
7 Lochhead P, Hagan K, Joshi AD, et al. Association Between Proton Pump Inhibitor Use and Cognitive Function in Women. Gastroenterology. 2017 Oct;153(4):971-979. e4.
8 Malfertheiner P, Kandulski A, Venerito M. Proton-pump inhibitors: understanding
the complications and risks. Nat Rev Gastroenterol Hepatol. 2017 Dec;14(12):697- 710.
Dr Sarmed Sami
MBChB MRCP PGCME PhD
Consultant Gastroenterologist and Associate Professor
HCA London Digestive Centre and Mayo Clinic London
Honorary - University College Hospital and University College London
Founder and Director, Digestive Health UK
Founder and Director, LUGIS (London International Upper GI Symposium)
T: 0207 4594918
E: appointments@ digestivehealthuk.com
W: www.digestivehealthuk.com
Follow us on: LinkedIn, Facebook, Instagram
Vitamin B12 deficiency
Hypomagnesaemia Hypocalcaemia
Osteoporosis Bone fractures
Causal relationship
Low evidence for causallity Insufficient eveidence for causality
• Wanting to stop PPIs is not a good reason to have surgery (~70% patients required PPIs within 5 year of surgery and ~20% needed PPIs for >6 months)2
• PPIs have similar safety profile to anti-reflux surgery (two randomised controlled trials - LOTUS and SOPRAN addressed this question)3
Are PPIs safe long term?
The majority of data on risks from PPIs come from association studies (not causation studies) and those are usually either observational, poorly designed, retrospective,
or case series. There are only a few prospective, adequately powered, large scale epidemiological studies with long term follow up data. Out of those, only a few show evidence of harm from PPIs.
Calcium and magnesium absorption: In a randomised, placebo-controlled trial including 12 healthy volunteers in a crossover design, inhibition of gastric acid secretion by PPI intake did not affect the absorption of calcium4. Moreover, in the analysis of 2 randomised control trials with up to 12 years of follow up, no differences in calcium and vitamin D serum levels were observed between groups, with or without PPI use3.
Osteoporosis and bone fracture: Two large prospective studies to date addressed this question. One with 79,899 women and 565,786 person years follow-up. Hip fractures in PPI users = 2.02 events per 1000 person years and PPI non-users =
1.51 events per 1000 person years. Overall hazard ratio (HR) 1.35 (95% confidence interval (CI) 1.13-1.62). After excluding smokers, HR = 1.06 (95% CI 0.77 to 1.46)5. The summary point here is that the absolute risk (2.02 per 1000 person years) remains extremely low in PPI users. The risk also remains present in PPI non-users. In patients who need PPIs, the benefits certainly outweigh any risks. A second study with 130, 487 women and 1,005,126 person years of follow-up showed no association with hip fractures or bone mineral density change, but modest association with clinical spine, forearm or wrist, and total fractures. HR = 1.25 (95% CI 1.15-1.36)6
Dementia and cognitive impairment: The largest prospective cohort study to
date (n=13,864 women with 14 year follow up) showed that PPI users are more likely to have other chronic medical conditions (cardiovascular disease, diabetes), use antidepressants/aspirin, be less physically active, have higher BMIs, but no difference in cognitive scores compared to non-PPI users7.
Details on other adverse events with proven and unproven causality are summarised in Figure 2.
Conclusions
PPIs remain highly effective and safe in the right patient. PPI use must be based on objective and clear evidence base for benefit, otherwise we may risk causing more harm to patients. We suggest the above approach to help clinicians in navigating decisions about whether or not to prescribe PPIs and for how long. Specialist opinion and modern testing techniques for GORD can be utilised in order to reduce harm from PPIs and target their use at the right patient.
Figure 2. PPIs and adverse events with proven and unproven causality8 (SIBO = small intestinal bacterial overgrowth).
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