Gastroesophageal Reflux Disease

,; Chey, William D.

Applied Evidence

Gastroesophageal Reflux Disease

J Fam Pract. 2003 March;52(3):240-247

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References

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53. Chey WD, Inadmoni JM, Boojer AK, Fendrick AM. What do primary care physicians think about Barrett’s esoph-agus, the relationship between GERD and H. pylori, and treatment of nocturnal heartburn? Abstract presented at: DDW 2003; May 17-23, 2003; Orlando, Fla.

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Proton pump inhibitors. PPIs potently reduce gastric acid secretion by inhibiting the H⁺-K⁺adenosine triphosphatase pump of the parietal cell. As a result, they suppress gastric acid secretion for a longer period than H₂RAs.⁴⁵ Evidence from randomized, controlled trials has demonstrated the superiority of PPIs over any other class of drugs for the relief of GERD symptoms, for healing esophagitis, and for maintaining patients in remission. Standard doses of omeprazole, lansoprazole, panto-prazole, esomeprazole, and rabeprazole have, for the most part, shown comparable rates of healing and remission in erosive esophagitis.^46-52

PPIs are best absorbed in the absence of food. Ingestion of food after a PPI stimulates parietal cell activity when blood levels of the PPI are increasing; this promotes uptake of the PPI by the parietal cells. Therefore, patients should be advised to take their PPI between 30 and 60 minutes before eating. For patients on a once-daily PPI, the best time to take it is about 30 to 60 minutes before breakfast. Despite these recommendations, a recent survey of over 1000 US primary care physicians found that 36% instructed their patients to take their PPI with or after a meal or did not specify the timing of dosing.⁵³

Guidelines for proton pump inhibitor use in clinical practice

Clinical evidence indicates that a trial with a PPI provides the quickest and most cost-effective method for diagnosing GERD. Despite this, many physicians use a trial of H₂ receptor antagonists prior to initiation of PPI therapy.

Clinicians should clearly instruct their patients regarding optimal timing of the dose, since this can have a significant effect on the success of therapy.
Patients for whom antireflux surgery is being considered should first be referred for consultation with a gastroenterologist to assist in patient selection, to ensure that appropriate preoperative evaluation has been performed and to help exclude other possible causes of their symptoms.^21,54

PPI therapy can be tailored to control GERD symptoms. Treatment can start with the most effective dosage and then be stepped down, or start with a minimum dosage and then be stepped up (Table 2). Patients with predominantly daytime symptoms should take PPIs before breakfast. Concerns that were once expressed about the long-term use of PPIs, such as predisposing patients to stomach cancer, have been refuted by extensive clinical experience and intensive monitoring (Table 3).³

TABLE 1

Over-the-counter therapy for GERD

Prevention and rapid relief of symptoms Reduction of frequency and severity of symptoms Role in therapy Limitations
Adapted from Peterson, WL.GERD:Evidence-based therapeutic strategies.
Bethesda, Md.:American Gastroenterological Association;2002.

TABLE 2

Step-down and step-up treatments: advantages and disadvantages

Regimen	Advantages	Disadvantages
Step-down therapy (high-dose initial therapy)	Rapid symptom relief	Potential overtreatment
	Efficient for physician	Higher initial drug cost
	Avoids overinvestigation and associated costs	Higher initial drug cost
Step-up therapy (minimum-dose initial therapy)	Avoids overtreatment	Patient may continue with symptoms unnecessarily
	Lower initial drug cost	Inefficient for physician
		May lead to overinvestigation
		Uncertain end point (partial symptom relief)
Adapted from Dent J, et al. Management of gastro-oesophageal reflux disease in general practice.BMJ 2001;322:344-347.

TABLE 3

Potential concerns associated with the use of proton pump inhibitors

Potential concern	Level of Evidence*	Grade ^†	Comments
Long-term PPI treatment may lead to reduced serum cobalamin levels	2b	B	This is most likely to occur in individuals with atrophic gastritis
Increased acid output has been seen after stopping a PPI	2b	B	Effects of PPI treatment on corpus glandular atrophy in H pylori-infected individuals are difficult to interpret due to possible sampling error and short study duration
PPI treatment may predispose to bacterial enteric infection	3	B	Only shown in a single case control study
*Level of evidence:1, Evidence for and/or general agreement that treatment is useful and effective;1a, systematic review with homogeneity of randomized controlled trials (RCTs);1b, individual RCTs (with narrow confidence interval);2, conflicting evidence and/or divergent opinion about efficacy and use;2a, evidence or opinion is in favor of treatment;2b, use and efficacy is less well established by evidence or opinion;3, evidence and/or general agreement that treatment is not useful or effective and may be harmful in some cases.
†Quality grading:A, well-designed, clinical trials;B, well-designed cohort or case-control studies;C, case reports, flawed trials;D, personal clinical experience;E, insufficient evidence to form opinion.
Adapted from Peterson, WL.GERD:Evidence-based therapeutic strategies. Bethesda, Md:American Gastroenterological Association, 2002.

Surgery

Surgical antireflux therapy is an option in carefully selected patients. Those who respond best to surgical therapy will have had clearly documented acid reflux, typical symptoms, and symptomatic improvement while on PPI treatment.⁵⁴

Unfortunately, a recent survey suggests that physicians tend to recommend surgery for patients in whom medical therapy has failed.⁵³ However, patients who failed to respond to PPI therapy are unlikely to have GERD and, therefore, are highly unlikely to have a good outcome from antireflux surgery. Recent studies suggest that up to 62% of patients who have had open surgery for GERD continue to require medical treatment afterward. Although some studies demonstrate that surgery has greater efficacy over medical therapy initially, long-term follow-up has shown that surgically treated patients often need further medical therapy for persistent GERD symptoms.⁵⁵ Community-based studies of antireflux surgery indicate that many patients develop new symptoms that they did not have before surgery and that these substantially diminish quality of life.

New endoscopic therapies, including radiofrequency energy delivery to the region of the lower esophageal sphincter and endoscopic suturing, have recently been approved for use by the FDA. This approval was based largely on safety rather than efficacy data. Clinical evidence is limited to uncontrolled studies in patients with no or mild esophagitis.³ These techniques should not be used in preference to established medical treatment unless and until data from randomized, controlled trials become available that demonstrate safety and efficacy.⁵⁶