Literature Review of Major Guidelines and Recommendations for Uses of Acid Suppression Therapy
[Also available as downloadable pdf below]
Major guidelines published in the past few years
ACG guidelines from March 20171
Best Practice Advice 1: Patients with GERD and acid-related complications (i.e., erosive esophagitis or peptic stricture) should take a PPI for short-term healing and for long-term symptom control.
Rationale: PPIs are highly effective in healing esophagitis and for GERD symptom control, and this benefit is likely to outweigh PPI-related risks. There is no evidence for or against PPIs in asymptomatic patients with healed esophagitis or for PPIs beyond 12 months.
Best Practice Advice 2: Patients with uncomplicated GERD who respond to short-term PPIs should subsequently attempt to stop or reduce them. Patients who cannot reduce PPIs should consider ambulatory esophageal pH/impedance monitoring before committing to lifelong PPIs to help distinguish GERD from a functional syndrome. The best candidates for this strategy may be patients with predominantly atypical symptoms or those who lack an obvious predisposition to GERD (eg, central obesity, large hiatal hernia).
Rationale: Short-term PPIs are highly effective for uncomplicated GERD. Most patients with uncomplicated GERD respond to short-term PPIs and are subsequently able to reduce PPIs to less than daily dosing. Because patients who cannot reduce PPIs face lifelong therapy, we would consider testing for an acid-related disorder in this situation. However, there is no high-quality evidence on which to base this recommendation.
Best Practice Advice 3: Patients with Barrett’s esophagus and symptomatic GERD should take a long-term PPI.
Rationale: PPIs have a clear symptomatic benefit and a possible benefit in slowing progression of Barrett’s. There is likely to be a net benefit for long-term PPIs in these patients.
Best Practice Advice 4: Asymptomatic patients with Barrett’s esophagus should consider a long-term PPI.
Rationale: The evidence that PPIs slow progression of Barrett’s is low in quality but the evidence of PPI adverse effects is also low in quality. Because there is no high quality evidence on either side of this question, this is a weak recommendation and this decision should be individualized with patients.
Best Practice Advice 5: Patients at high risk for ulcer-related bleeding from NSAIDs should take a PPI if they continue to take NSAIDs.
Summary table of AGA/ACG guideline recommendations from July 20162
The authors “suggest that patients taking PPIs for GERD stop therapy >2 weeks after symptoms resolve, use H2RAs or antacids for infrequent symptoms, employ adjunctive life-style modifications, and institute intermittent PPI courses of ≥2–4 weeks for symptom recurrence (≥2 episodes per week). On-demand therapy is also reasonable.”
Summary table in BMC Medicine on recommendations in 20163
Data for prophylaxis when taking specific other medications that modify risk
The population considered to be at increased risk in the above guidelines is taken from 2009 ACG guidelines published in the American Journal of Gastroenterology:4
Per the 2016 ACC/AHA guidelines on dual antiplatelet therapy for patients with coronary artery disease, “PPIs should be used in patients with a history of prior gastrointestinal bleeding treated with DAPT (Class I). In patients with increased risk of gastrointestinal bleeding, including those with advanced age and those with concomitant use of warfarin, steroids, or nonsteroidal anti-inflammatory drugs, use of PPIs is reasonable (Class IIa). Routine use of PPIs is not recommended for patients at low risk of gastrointestinal bleeding (Class III: No Benefit)”5 This and other guidelines base their recommendations on this 2008 guideline published in Circulation:6
Regarding clopidogrel use specifically, the recommendations reference is a 2010 study published in NEJM.7 In this study, the trial was terminated prematurely due to the sponsor losing financing, but enrolled 3873 of the intended 5000 patients. All patients were on clopidogrel and aspirin, and were randomized to get omeprazole versus placebo. Gastrointestinal event rate was 1.1% with omeprazole with 2.9% with placebo t 180 days (hazard ratio 0.34 with omeprazole, 95% CI 0.18 to 0.63, p< 0.001). No significance difference in cardiovascular events or serious adverse events. They concluded that “Among patients receiving aspirin and clopidogrel, prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding. There was no apparent cardiovascular interaction between clopidogrel and omeprazole, but our results do not rule out a clinically meaningful difference in cardiovascular events due to use of a PPI.“
There are no recommendations for AST use for patients on corticosteroids individually, except in the context of concurrent use of anti-platelets or NSAIDs per above. The BMC recommendations state that “corticosteroid therapy does not cause damage to the gastroduodenal mucosa, but can enhance the GI risk associated with NSAID use. Therefore, unless patients taking corticosteroid therapy have a PU or are under concomitant NSAID therapy, mucosal protection with a PPI is not routinely indicated.”3 A NYU professor discusses the data available in this online institutional publication, also concluding that there is no increased ulcer risk from corticosteroids themselves, but may impair wound-healing to exacerbate ulcers caused by other etiologies like NSAIDs.8
A systematic review and meta-analysis in BMJ Open from 2014 suggests that corticosteroid use was associated with increased risk of GI bleed and perforation in hospitalist patients (OR 1.42, 95% CI 1.22 to 1.66).9 But, none of the guidelines suggest PPI prophylaxis for patients on corticosteroids solely for being hospitalized, perhaps since this meta-analysis did not define a particular population among hospitalized patients and it drew from a diverse set of studies, included patients in the ICU, and spanned studies as early as 1983, after which time h.pylori was discovered and treated and would impact rates of GI bleeds.
Stress ulcer prophylaxis:
This is not discussed in the 2017 ACG guidelines, or the 2016 AGA/ACG guidelines. Per the BMI guidelines:
“PPIs are the drugs of choice for acid suppression in SUP. The risk of bleeding in intensive care unit (ICU) is reduced by some 60 % in patients receiving SUP compared with those treated with placebo or no prophylaxis. Routine prophylaxis, however, is not justified by current evidence. SUP should be withheld in the majority of hospitalized patients, unless they have multiple risk factors, since only those at risk of clinically important bleeding (CIB) are most likely to benefit from preventive strategies. Educating clinicians to follow SUP guidelines can improve the cost-effectiveness of PPI use in this clinical setting.“3
Risks of acid suppression therapy
The 2017 ACG guidelines1 summarize the studied risks as being of low evidence currently, as all are based on observational data. The table summarizes the relative and absolute risks associated with the studied adverse effects, where the absolute risk is shown to be small except for CDI.
We recommend that patients take long-term PPIs for complicated GERD, uncomplicated GERD with objective evidence of excess acid, Barrett’s esophagus with GERD symptoms, and NSAID bleeding prophylaxis if high-risk. For patients who do not fall into these categories, the lack of solid evidence means that the risk-benefit equation is less clear.”1
The goal then is to minimize the AST
in patients with no clear indication, since, even if the risks are low, the
risks still outweigh zero benefit.
This was compiled in April 2017 by Sonali Palchaudhuri, Johns Hopkins Bayview Medical Center