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Acid Suppression Therapy

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.
Rationale: PPIs are highly effective in preventing ulcer-related bleeding in appropriately selected patients who take NSAIDs, and this benefit is likely to outweigh PPI-related risks.

Best Practice Advice 6: The dose of long-term PPIs should be periodically reevaluated so that the lowest effective PPI dose can be prescribed to manage the condition.
Rationale: Long-term PPI users often receive PPIs at doses higher than necessary to manage their condition. Since PPI reduction is often successful, it is logical to periodically reevaluate PPI dosing so that the minimum necessary dose is prescribed.

Best Practice Advice 7: Long-term PPI users should not routinely use probiotics to prevent infection.
Rationale: There is no evidence for or against probiotics to prevent infections in long-term users of PPIs.

Best Practice Advice 8: Long-term PPI users should not routinely raise their intake of calcium, vitamin B12 or magnesium beyond the Recommended Dietary Allowance (RDA).
Rationale: There is no evidence for or against use of vitamins or supplements beyond the RDA in long-term users of PPIs. Many adults fall below the RDA in several vitamins or minerals and, in these adults, it is reasonable to raise intake to meet the RDA regardless of PPI use.

Best Practice Advice 9: Long-term PPI users should not routinely screen or monitor bone mineral density, serum creatinine, magnesium, or vitamin B12.
Rationale: There is no evidence for or against dedicated testing for patients taking long-term PPIs. Such screening (eg, for iron or vitamin B12 deficiency) can be offered but is of no proven benefit.

Best Practice Advice 10: Specific PPI formulations should not be selected based on potential risks.
Rationale: There is no convincing evidence to rank PPI formulations by risk.

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

NSAID use:

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

 

Anti-platelet use

Per the 2016 ACC/AHA guidelines on dual antiplatelet therapy for patients with coronary artery disease, “PPIs should be used in patie

nts 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.“

Corticosteroid use

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

Conclusion

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.  

References

  1. Freedberg DE, Kim LS, Yang Y. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-715. doi:10.1053/j.gastro.2017.01.031.
  2. Laine L, Nagar A. Long-Term PPI Use: Balancing Potential Harms and Documented Benefits. Am J Gastroenterol. 2016;111(7):913-915. doi:10.1038/ajg.2016.156.
  3. Scarpignato C, Gatta L, Zullo A, Blandizzi C, Group S. Effective and Safe Proton Pump Inhibitor Therapy in Acid-Related Diseases – A Position Paper Addressing Benefits and Potential Harms of Acid Suppression. BMC Medicine; 2016. doi:10.1186/s12916-016-0718-z.
  4. Lanza FL, Chan FKL, Quigley EMM, Parameters P. Guidelines for Prevention of NSAID-Related Ulcer Complications. Am J Gastroenterol. 2009;104(March):728-738. doi:10.1038/ajg.2009.115.
  5. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC / AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease. J Am Coll Cardiol. 2016;68(10). doi:10.1016/j.jacc.2016.03.513.
  6. Bhatt DL, Scheiman J, Abraham NS, et al. Expert Consensus Document ACCF / ACG / AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use A Report of the American College of Cardiology Foundation Task Force. Circulation. 2008;118:1894-1909. doi:10.1161/CIRCULATIONAHA.108.191087.
  7. Cohen M, Lanas A, Sc D, et al. Clopidogrel with or without Omeprazole in Coronary Artery Disease. N Engl J Med. 2010;363(20):1909-1917.
  8. Fakheri RJ. Corticosteroids and Prophylaxis. What complications should you try to prevent in patients on chronic corticosteroids? Clinical Correlations: The NYU Langone Online Journal of Medicine. http://www.clinicalcorrelations.org/?p=6569. Published 2013. Accessed March 20, 2017.
  9. Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open. 2014;4:1-10. doi:10.1136/bmjopen-2013-004587.

 

This was compiled in April 2017 by Sonali Palchaudhuri, Johns Hopkins Bayview Medical Center

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Sonali Palchaudhuri,
Apr 11, 2017, 11:57 AM
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