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This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

Based on an article in the journal Gastroenterology 2004;126:660-4.

July 2008

Reported by: Gilbert Doummar, MD, FRCPC

Chief, Department of Gastroenterology Centre hospitalier Pierre-Boucher Longueuil, Quebec

Gastroesophageal reflux disease (GERD) is defined by frequent and recurrent reflux of gastric contents into the esophagus. Although heartburn is the dominant symptom, a broad array of other complaints may be GERD-related, including acid regurgitation, dyspepsia, nausea, and non-specific complaints of abdominal discomfort. When defined as at least one bothersome symptomatic episode per week, surveys suggest that about 20% of adults have GERD. In the elderly, the incidence of GERD symptoms is similar but the risk of esophagitis is greater. While only about half of patients under the age of 60 complaining of GERD have readily identifiable erosive esophagitis when evaluated endoscopically, rates as high as 80% have been reported in those older than age 60.

Despite the increased likelihood of esophagitis in the elderly, some studies have documented a reduction in the incidence of GERD. This is consistent with studies of visceral sensitivity. In a study that employed graded intraesophageal balloon distension, the threshold of pain increased with increasing age. The reduction in somatic complaints observed among elderly patients is not confined to the gastrointestinal (GI) track. For example, the severity of chest pain in elderly patients experiencing a myocardial infarction is also reduced, and the frequency of silent ischemia is greater.

In GERD, the increased likelihood of diminished or even silent symptoms extends to Barrett’s esophagus, a precancerous state characterized by esophageal metaplasia. Not only have elderly patients with Barrett’s esophagus been reported to have fewer symptoms than younger patients, but nearly one-third of elderly patients who progressed to adenocarcinoma had minimal or no symptoms at the time of diagnosis. This lack of correlation is of particular concern because the risk of both Barrett’s esophagus and adenocarcinoma of the esophagus increases with age.

In pooled data from five clinical trials with 11,945 patients over the age of 18, an inverse correlation was observed between older age and presence of symptoms, but there was a strong positive correlation between age and presence of severe esophagitis. These and other data support the conclusion that more aggressive investigation and treatment of GERD may be necessary in the elderly independent of the severity of symptomatic complaints.

Patient Evaluation

Due to the unpredictable relationship between symptoms and presence of esophagitis, an update of the Canadian consensus recommendations on the treatment of GERD has removed the age restriction for the use of endoscopy in the absence of alarm symptoms, such as unexplained weight loss. Previously, a one-time endoscopy was recommended in individuals over the age of 50. The revised recommendation is to screen any patient with GERD symptoms for 10 or more years for Barrett’s epithelium. In the elderly with new-onset GERD, endoscopy should be considered early in the course of disease due to the increased potential for erosive esophagitis and development of Barrett’s epithelium. Again, the decision to perform or refer for an endoscopy should not be symptom-dependent.

In the elderly, an endoscopic evaluation is not urgent in a patient with a previous diagnosis of GERD who readily responds to re-initiation of proton pump inhibitor (PPI) therapy. In individuals with new-onset symptoms, it is reasonable to initiate PPI therapy without first performing endoscopy, but a subsequent endoscopy should be performed. One reasonable approach is to conduct an endoscopic evaluation four weeks after initiating therapy. Although patients with mild to moderate esophagitis, known in the Los Angeles (LA) classification system as grade A (mucosal breaks of no greater than 5 mm in length) or grade B (mucosal breaks greater than 5 mm but not extending over more than one mucosal fold) disease, may have healed within this treatment period, endoscopy permits screening of other pathologies, such as gastric ulcers. Those with LA esophagitis grades of C (mucosal break continuous over two mucosal folds) and D (mucosal breaks over 75% or more of the esophageal circumference) are not likely to be fully healed within four weeks, but an endoscopic evaluation provides a baseline for assessing disease severity and will confirm that healing is underway.

Most importantly in the elderly, a control endoscopy at four weeks allows patients to be screened for Barrett’s esophagus, which reaches a peak incidence at about age 70. The presence of Barrett’s esophagus has an important impact on treatment, particularly in defining a need for regular cancer surveillance.

The approach to evaluation and treatment of GERD in the elderly is straightforward in patients presenting with classic symptoms of heartburn, but the challenge in the elderly is the increased risk of atypical symptoms, such as loss of appetite, nausea, or dyspepsia that do not clearly correspond with the lower esophagus. In these patients, it may be appropriate to conduct an endoscopy without first initiating PPI therapy in order to correlate pathology with symptoms. However, a trial of PPI should not be withheld when quality of life is compromised by symptoms even if the risk is healing of lesions prior to a definitive diagnosis. In the context of symptom relief with PPIs and the absence of lesions of endoscopy, an acid-related pathology can be reasonably assumed.

Treatment of GERD in the Elderly

According to the most recent Canadian Consensus Conference guidelines, lifestyle modifications are ineffective as an isolated approach to control of frequent or severe GERD even in individuals without esophagitis. Antacids are often effective for symptom relief, but benefit is transient, and these are not effective for healing. H2-receptor antagonists are more effective than antacids for symptomatic relief of GERD, but their efficacy in chronic dosing is compromised by tachyphylaxis. More importantly for those with esophagitis, H2-receptor antagonists are relatively ineffective for healing. While overall healing rates on H2-receptor antagonists have been as high as 45% after 12 weeks of therapy in some clinical trials, there is diminishing efficacy with increasing severity of the esophagitis even with an extended treatment course.

PPIs are currently the most effective therapy for GERD. The greater effect of PPIs relative to H2-receptor antagonists can be directly correlated with more complete acid control. Relative differences between PPIs underscore this relationship. Although all PPIs are highly effective for control of GERD symptoms, particularly relative to H2-receptor antagonists, agents within this class differ for relative acid control and for relative healing of esophagitis. Of the currently available agents, esomeprazole, which is the S-isomer of omeprazole, the first PPI licensed for clinical use, has consistently demonstrated greater acid control when each PPI is compared in conventional doses as measured by proportion of time with pH >4 over a 24-hour dosing period. This increase in 24-hour acid control predicts more effective healing of esophagitis, which has now been demonstrated in studies comparing esomeprazole to omeprazole, its parent drug, as well as lansoprazole and pantoprazole.

In the esomeprazole-lansoprazole comparison, 5241 patients with documented erosive esophagitis were randomized to receive esomeprazole 40 mg or lansoprazole 30 mg. At the end of the eight-week treatment period, healing was achieved in 92.6% of patients randomized to esomeprazole vs. 88.8% of those randomized to lansoprazole (P=0.0001) on an intent-to-treat basis. Both agents were well tolerated.

Results were similar in the esomeprazole-pantoprazole comparison called EXPO (The Efficacy of Healing and Maintenance Treatment with Esomeprazole and Pantoprazole in Subjects with Reflux Esophagitis). Healing at eight weeks was achieved in 96% of patients randomized to esomeprazole 40 mg vs. 92% of those randomized to pantoprazole 40 mg (P<0.001).

Subsequent analyses of the EXPO study demonstrated that the differences in healing increased with esophagitis grade. While the advantage for esomeprazole over pantoprazole was non-significant for LA grade A, the incremental benefit increased with each LA grade, underscoring the important relationship between degree of acid control and likelihood of healing in severe disease. These results have particular relevance to an elderly population with an increased likelihood of higher grades of esophagitis.

Similar differences have been observed for maintenance of healing relative to acid control. While PPIs are more effective for preventing relapses than H2-receptor antagonists, the PPI that provides the greatest 24-hour acid control has also been associated with greatest protection from relapse in well-controlled trials. For example, in an extension of the EXPO study that included 2766 patients who had healed on therapy, 87% for those receiving esomeprazole 20 mg vs. 74.9% of those receiving pantoprazole 20 mg (P<0.0001) remained in symptomatic remission at the end of six months (Figure 1). There were also fewer discontinuations for recurrent symptoms. A similar advantage for esomeprazole relative to lansoprazole has been demonstrated for maintenance.

Figure 1. Endoscopic and Symptomatic Remission Following Six Months of Maintenance Therapy

Maintenance Strategies

GERD is a chronic disease in approximately 80% of patients, which means that most patients will require a maintenance regimen for long-term disease control. Although as-needed treatment is considered acceptable for younger patients, it may be inappropriate in the elderly due to the greater disconnect between symptoms and the return of reflux threatening recurrent esophagitis. Similarly, half-dose maintenance regimens have been promoted in some countries on the basis that the slight reduction in efficacy is justified by more cost-effective therapy. This relationship is not true in Canada, where a half-dose is the same price as a full dose. In the elderly, who may require more intensive acid control to control a higher risk of severe esophagitis, a half-dose strategy is particularly unattractive.

The presence or absence of Helicobacter pylori is not relevant to the management of GERD. Specific screening for this infection is not warranted, although a biopsy of the gastric mucosa in the course of an endoscopic evaluation is a reasonable step to address gastritis. While eradication of H. pylori has theoretical benefits in reducing the lifetime threat of gastric carcinoma, the purported benefit in the elderly would be expected to be reduced by the reduced lifespan in which malignant transformation can occur.

Primary-care physicians are well suited to manage GERD in the elderly. If patients spontaneously complain of upper GI symptoms, further evaluation is obviously warranted. However, patients should be asked specifically about GI function as part of a systematic physical examination that considers all body systems. Questions regarding eating habits, discomfort, or blood in stool should all be cues to consider the potential presence of GI pathology. In older patients, physicians need to be more sensitive to the potential of GERD as a factor in such non-specific symptoms as loss of appetite or mild nausea even in the absence of heartburn. Similar to the ability of PPIs to rapidly relieve heartburn, atypical symptoms associated with GERD typically resolve rapidly with effective therapy.

Summary

The principles of the diagnosis and management of GERD require modification in the elderly. Although GERD is no more common in this patient population, it tends to be less symptomatic even though the risk of severe esophagitis is greater. Moreover, the elderly are at greater risk of Barrett’s esophagus and esophageal adenocarcinoma. In the elderly, endoscopy should be used relatively early in the course of the disease to rule out significant pathology. In addition, more intensive therapy may be warranted both for healing of esophagitis and prevention of relapse. Relative differences in acid control for available therapies, including agents within the PPI class, are likely to have greater relevance to the elderly due to the increased likelihood of significant esophagitis.