Evidence
This page contains a snapshot of featured content which highlights evidence addressing key clinical questions including areas of uncertainty. Please see the main topic reference list for details of all sources underpinning this topic.
BMJ Best Practice evidence tables
Evidence tables provide easily navigated layers of evidence in the context of specific clinical questions, using GRADE and a BMJ Best Practice Effectiveness rating. Follow the links at the bottom of the table, which go to the related evidence score in the main topic text, providing additional context for the clinical question. Find out more about our evidence tables.
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and there is a trade off between benefits and harms of the intervention.
Population: People with an indication for long-term PPI use including GERD, Barrett’s esophagus, and nonsteroidal anti-inflammatory drug (NSAID) bleeding prophylaxis ᵃ
Intervention: Long-term use of PPIs (not further defined) ᵇ
Comparison: No PPIs
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Chronic kidney disease | Occurs more commonly with PPIs compared with no PPIs (favors comparison) | Very Low ᶜ |
Dementia | Occurs more commonly with PPIs compared with no PPIs (favors comparison) | Very Low ᶜ |
Bone fracture | Occurs more commonly with PPIs compared with no PPIs (favors comparison) | Low or Very Low ᵈ |
Myocardial infarction | No statistically significant difference ᵉ | Very Low |
Small intestinal bacterial overgrowth | Occurs more commonly with PPIs compared with no PPIs (favors comparison) | Low |
Campylobacter or Salmonella infection | Occurs more commonly with PPIs compared with no PPIs (favors comparison) | GRADE assessment not performed for this outcome |
Spontaneous bacterial peritonitis | Occurs more commonly with PPIs compared with no PPIs (favors comparison) | Very Low ᶜ |
Clostridium difficile infection | No statistically significant difference | Low ᶜ |
Pneumonia | No statistically significant difference ᵉ | Very Low |
Micronutrient deficiencies | Occurs more commonly with PPIs compared with no PPIs (favors comparison) | Low or Very Low ᵈ |
Gastrointestinal malignancies | No statistically significant difference ᵉ | Very Low |
Recommendations as stated in the source guideline Patients with uncomplicated GERD who respond to short-term PPIs should subsequently attempt to stop or reduce them. Patients with Barrett’s esophagus and symptomatic GERD should take a long-term PPI. The dose of long-term PPIs should be periodically re-evaluated so that the lowest effective PPI dose can be prescribed to manage the condition.
Note Overall the guideline committee concluded that when PPIs are prescribed appropriately their benefits are likely to outweigh the risks. However, the risk:benefit ratio should be kept in mind as the modest risks will become more important as benefit to the individual patient decreases. The guideline committee noted that baseline differences between PPI users and non-users mean there are some challenges in interpreting the risks based on data from retrospective, observational studies. ᵃ It is unclear from the information in the published guideline as to what proportion of the population in the identified evidence had GERD. However, the guideline authors felt that the risks of long-term PPI use were unlikely to be dependent on the underlying diagnosis. ᵇ The authors assumed a class effect for PPIs due to the lack of high-quality evidence illustrating differing adverse event results between different PPI formulations. ᶜ Based on observational studies only. ᵈ The outcomes bone fracture and micronutrient deficiencies were graded as “Low or Very Low” by the guideline committee; this is possibly due to variation in the evidence for different deficiencies (magnesium, calcium, iron, and vitamin B12) and for bone fracture versus bone mineral density. However, this is unclear in the published guideline. ᵉ This outcome is underpinned by observational and RCT evidence which have produced differing results with RCTs showing no statistically significant difference. A subsequent large RCT on long-term safety of PPIs (published 2019) also showed no statistically significant difference.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and there is a trade off between benefits and harms of the intervention.
Population: Adults (>16 years of age) with GERD judged to be suitable for either surgical or medical management (excluding patients who have symptomatic esophageal stricture due to GERD or those who have esophageal dysplasia or cancer).
Intervention: Laparoscopic fundoplication
Comparison: Medical management (proton-pump inhibitor)
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Health‐related quality of life: <1 year and 1-5 years | No statistically significant difference | Very Low |
GERD‐related quality of life: <1 year | Favors intervention | Low |
GERD‐related quality of life: 1-5 years | No statistically significant difference | Very Low |
Heartburn: <1 year, 1-5 years, and ≥5 years | Favors intervention | Very Low |
Reflux: <1 year and 1-5 years | Favors intervention | Very Low |
Reflux: ≥ 5 years | No statistically significant difference | Very Low |
Dysphagia: <1 year and 1-5 years | Favors comparison | Very Low |
Dysphagia: ≥5 years | No statistically significant difference | Very Low |
Serious adverse events | Occurs more commonly with laparoscopic fundoplication compared with medical management (favors comparison) | Very Low |
Adverse events | No statistically significant difference | Very Low |
Note The Cochrane Clinical Answer (CCA) notes that due to the predominance of men within a narrow age range (42-48 years of age), these results may not be replicated in women, young adults, or the elderly, and that there is also insufficient evidence to support or refute the use of fundoplication (both laparoscopic and open) over treatment with proton-pump inhibitors in adults with GERD.
This evidence table is related to the following section/s:
Cochrane Clinical Answers
Cochrane Clinical Answers (CCAs) provide a readable, digestible, clinically focused entry point to rigorous research from Cochrane systematic reviews. They are designed to be actionable and to inform decision making at the point of care and have been added to relevant sections of the main Best Practice text.
- What are the benefits and harms associated with de-prescribing long-term proton pump inhibitor therapy in adults?
- In adults with gastro-esophageal reflux disease, is there randomized controlled trial evidence to support the use of laparoscopic fundoplication surgery instead of medical management?
- What are the benefits and harms associated with de-prescribing long-term proton pump inhibitor therapy in adults?
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