Improving Pharmaceutical Care of the Elderly Patient With GERD

Learning ObjectivesAfter completing this continuing education article, the reader should be better able to:

• Explain the economic burden of GERD in the elderly in the United States.

• Understand the risk factors associated with GERD.

• Review the diagnosis and complications of GERD as well as the goals of therapy.

• Specify atypical symptoms of GERD common in the elderly patient population.

• Institute strategies to optimize pharmacologic therapy in elderly patients being treated for GERD (eg, proper dosing and monitoring for signs of adverse events).

Gastroesophageal reflux disease (GERD) is defined as the symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus.¹ Left untreated, GERD can be associated with unpleasant symptoms as well as a number of complications.

The epidemiology and presentation of GERD in elderly populations is somewhat different than in younger patients. Likewise, elderly patients have unique characteristics that influence management. The purpose of this article is to discuss the symptomatology, pathophysiology, presentation, diagnosis, and management of GERD as they apply to elderly patients.

Epidemiology

The overall prevalence of GERD has been estimated at 10% to 20% in the Western world, and nearly 20 million Americans suffer from the disease.² The prevalence of GERD appears to be similar in young and elderly patients. Although the prevalence of GERD is not higher in the elderly, the frequency of complications such as esophagitis, stricture, and Barrett's esophagitis is higher in older patients.³ In the Western world, the incidence of GERD is approximately 5 per 1000 person-years.⁴

The effect of increasing age on the incidence of GERD is unclear, with some studies showing an association with increasing age,^5,6 others suggesting no association,⁷ and still others suggesting an increasing incidence up to a certain age (55-70 years) and then a decline.^8,9 Taken together, the data suggest that the incidence of GERD symptoms does not increase with aging. As the population ages, however, the number of elderly patients with GERD will, of necessity, increase.

Social and Economic Impact

The impact of untreated GERD on health-related quality of life (QOL) is marked and often underappreciated. GERD substantially impacts patients in a number of ways, including symptoms, complications, and inconvenience of treatment. QOL may be affected by disrupted sleep, reduced concentration at work, and interference with daily activities such as exercise, housework, or gardening. Some authors have suggested that the impact on QOL is similar in magnitude to that of such disorders as angina pectoris or congestive heart failure.²

Although GERD itself is seldom lifethreatening, prolonged or severe disease may lead to complications. As one might expect, these complications carry with them significant impairment of QOL. Elderly patients tend to present with complicated disease more frequently and therefore may be disproportionately affected relative to younger patients.

The economic burden of GERD also is substantial, with nearly $10 billion in direct costs alone. It is one of the 5 most costly gastrointestinal disorders.² In 2004, GERD was responsible for more than 5.5 million outpatient clinic appointments, while dyspepsia and gastritis accounted for an additional 2.2 million visits.¹⁰ In 2004, more than 8 million prescriptions were filled for proton pump inhibitors (PPIs) alone, and the total cost of PPIs in 2004 was more than $10 billion, including over-the-counter (OTC) preparations.¹⁰

GERD also has been shown to be responsible for decreases in work productivity. These losses appear to be directly related to the severity of symptoms as well as to the presence of nocturnal symptoms.² Data from Japan suggest that work productivity is further diminished by the need for physician office visits related to GERD.¹¹ These data imply that control of symptoms and prevention of complications is a cost-effective approach to the management of GERD.

Risk Factors

A number of risk factors have been suggested for GERD, some of which may be more common in elderly populations. Data from a United Kingdom twin registry demonstrate a significant association with a parental history of reflux disease, as well as a higher concordance between monozygotic twins than between dizygotic twins.⁵ A second study of citizens of Olmsted County, Minn, demonstrated an association of GERD with a history of reflux disease in an immediate relative, but not with a history of reflux in the family of the spouse.⁷ These data suggest a genetic component to the development of GERD.

Although a clear association exists between pregnancy and GERD, no study has demonstrated sex as an independent risk factor.⁴ Other identified risk factors include increased body mass index,^5,8,9 the use of certain medications (eg, anticholinergic agents, nitrates, oral steroids),^5,8 and smoking.^6,7 No clear demonstration has been made between coffee or food intake and symptoms of GERD.¹²

Whereas age has not been shown to be an independent risk factor, older patients may be more likely to possess other risk factors. For instance, elderly people are known to take more medications than younger people, and many of the agents that they take, such as nitrates and nonsteroidal antiinflammatory drugs, are associated with GERD. Likewise, elderly patients are more likely to have hiatal hernias and diseases associated with GERD, such as neurologic and respiratory diseases.

Pathogenesis

The pathogenesis of GERD is multifactorial. The following are contributions:

- Abnormalities in physiologic barriers to reflux (ie, lower esophageal sphincter [LES])- Altered esophageal mucosal resistance

- Delayed gastric emptying³

Over time, reflux of gastric contents results in esophageal damage. The reflux barrier may be impaired by alterations in LES tone (including alterations caused by drugs) or the presence of a hiatal hernia.¹³ Although LES dysfunction never has been shown to increase with age, elderly patients more frequently take drugs that can alter LES tone and are more likely to have hiatal hernias.¹⁴

Elderly patients may have decreased resistance to acid exposure because of decreased saliva production and decreased esophageal motility.^15-17 Perhaps the most important risk factor for the development of severe reflux complications in the elderly is the cumulative injury to esophageal mucosa due to poorly controlled disease.³

A number of commonly used drugs may contribute to GERD (Table 1). These drugs may act by impairing LES tone or by directly injuring the esophageal mucosa.¹⁸ Often, the use of these medications is more common in elderly patients. A crucial component of the evaluation of any patient with suspected GERD is a review of the medication profile for potentially offending agents.

Additionally, some neurologic diseases may affect esophageal and gastrointestinal motility and/or tone and contribute to the development of GERD. Many of these diseases–such as diabetes, Parkinson's disease, stroke, and dementia–are more common among older patients. These factors must be taken into account in the evaluation of elderly patients with symptoms suggestive of GERD.

Presentation

The classic symptoms of GERD include heartburn, regurgitation, or both, which commonly occur after meals and especially after large or fatty meals. These symptoms often are aggravated by recumbency or bending forward and are relieved by antacids.¹

Interestingly, there are significant differences in the presentation of GERD in elderly patients, compared with that in younger people. Elderly patients are less likely to present with the classic symptoms and are more likely to present with dysphagia, vomiting, chest pain, and pulmonary difficulties. ^3,19 The absence of traditional symptoms may be related to decreased acidity of the gastric contents or decreased esophageal sensitivity with age. The symptoms that are more frequent in the elderly reflect the increased likelihood of presenting with erosive esophagitis or complicated GERD.³

The absence of traditional symptoms means that clinicians must be particularly vigilant in the detection and management of GERD in elderly patients. Extraesophageal complaints–such as chest pain that has been determined to be noncardiac,prolonged laryngitis, chronic cough, or hoarseness–are common in the elderly, and GERD must remain in the differential diagnosis when such complaints are present.

Diagnosis

Several strategies are available for the diagnosis of GERD. They include diagnosis based on symptoms, endoscopy, and esophageal pH monitoring (the gold standard). Esophageal monitoring is performed by passing a pH probe into the esophagus to just above the gastroesophageal junction. The probe is used to collect data regarding the pH of the lower esophagus, and thus to evaluate for the reflux of acidic gastric contents over the course of a 24-hour period.

Current guidelines suggest that it is reasonable to offer empiric therapy to patients who present with classic symptoms. It also is reasonable to assume a diagnosis of GERD in patients who respond to appropriate therapy.¹

More invasive modalities, such as endoscopy, should be pursued in patients who do not respond to therapy; when there are symptoms suggestive of complicated disease (eg, dysphagia, odynophagia, bleeding, weight loss, or anemia); and when the duration of symptoms is sufficient to place the patient at risk for Barrett's esophagus (generally >5-10 years).¹ Some authors have suggested that endoscopy be used early in the evaluation of all elderly patients due to the higher frequency of complicated disease concomitantwith less-severe symptoms.³ Consequently, any elderly patient suspected of having GERD should undergo physician evaluation so that the appropriate diagnosis may be made.

Therapeutic Options

The treatment of GERD in the elderly follows the same general principles as for younger patients. Because elderly patients are more likely to have erosive esophagitis or complicated disease, however, they often require more aggressive medical therapy.³

The first step in the treatment of GERD is lifestyle modifications, including alterations of dietary habits and mechanical methods to decrease the reflux of gastric contents (Table 2). Although these changes have been shown to decrease the exposure of the lower esophagus to acid, the true efficacy of these maneuvers never has been rigorously demonstrated. Furthermore, lifestyle modifications alone are unlikely to control symptoms in the majority of patients.¹

A number of pharmacologic options are available for the treatment of GERD. Conceptually, these agents target the dysmotility component of GERD (ie, promotility agents) or, more commonly, they decrease acid production in the stomach to decrease the caustic consequences of refluxed contents (ie, acid-suppressing or neutralizing agents). These agents include OTC antacids and antireflux agents (eg, alginic acid and sucralfate), promotility agents (eg, metoclopramide and cisapride), histamine receptor type 2 (H₂) antagonists, and PPIs.

Antacids and alginic acid have been shown to be more effective than placebo for the relief of symptoms triggered by meals.^20,21 The results of 2 long-term trials suggest that effective symptom relief can be achieved in ~20% of patients^22,23 and may be appropriate for the management of mild or intermittent symptoms. These agents must be used with caution in the elderly, however, due to toxicity and side effects, including salt overload, constipation, diarrhea, hypercalcemia, and interference with the absorption of other drugs, particularly antibiotics.¹

Prokinetic Agents

Two prokinetic agents, metoclopramide and cisapride, currently are available for the management of GERD. Conceptually, these agents are attractive, because poor esophagogastric motility–including LES dysfunction and delayed esophageal and gastric clearance–is a central component of GERD pathophysiology. These agents are effective, alone or in combination with H₂ antagonists, in the treatment of nonerosive reflux disease or mild esophagitis, particularly when they are associated symptoms of nausea, bloating, and vomiting.³ These agents also are useful in the management of diabetic patients who requently suffer from gastroparesis.

Because of its antidopaminergic activity, however, metoclopramide is associated with unacceptable side effects in up to one third of elderly patients. These side effects include muscle tremors, spasm, agitation, insomnia, drowsiness, confusion, and even tardive dyskinesia.²⁴ Although cisapride has fewer central nervous system side effects, it has been withdrawn from general availability in the United States due to QTc prolongation and the associated increased risk of ventricular arrhythmias. Cisapride is available only via a limited-access program to patients meeting strict criteria.

Acid-suppressing Agents

Acid-suppressing agents target the production of acid by parietal cells in the stomach. Physiologically, 3 pathways stimulate parietal cells to release acid into the stomach. These pathways are mediated by gastrin, histamine, and acetylcholine, respectively. Once stimulated, the parietal cells produce acid via an apical hydrogen-potassium adenosinetriphosphatase (ATPase), or the so-called proton pump. This enzyme releases hydrogen ions into the stomach in exchange for potassium ions, thus lowering the pH of the gastric lumen. This proton pump is the common final pathway for acid production.

Conceptually, acid secretion may be reduced by decreasing the stimulus to the parietal cell by blocking the gastrin-, acetylcholine-, or histamine-mediated pathway. No gastrin inhibitors are available currently. Anticholinergic agents are limited by their side-effect profile, including urinary retention, dry mouth, blurred vision, constipation, and cardiovascular toxicity. To date, only antagonists of the histamine pathway are clinically important.

H₂ Receptor Antagonists

H₂ receptor antagonists were introduced in the late 1970s, and currently 4 agents are available: cimetidine, famotidine, nizatidine, and ranitidine (Table 3). All of these agents are available OTC and are equal in efficacy when used at equivalent dosages. They are effective for the treatment of symptoms due to nonerosive reflux disease and for the healing of mild esophagitis. Higher doses of H₂ receptor antagonists are required, however, for the treatment of more severe disease. At these high doses, the clinical and cost effectiveness of H₂ blockers generally is surpassed by PPIs.¹

The safety profile of PPIs is excellent. Although the renal clearance of PPIs is reduced in elderly patients, no reduction in the dose of either omeprazole or lansoprazole is needed in the elderly, including those with renal or hepatic dysfunction.³⁶ The PPIs vary in the extent to which they are metabolized by the cytochrome P-450 system, and they may alter the metabolism of drugs such as warfarin. In patients taking warfarin, the use of newer PPIs may be preferred over omeprazole.³⁶

There has been some concern that the profound acid suppression of PPIs may decrease the absorption of vitamin B₁₂. This effect is secondary to the impaired secretion of intrinsic factor by parietal cells, which typically occurs parallel with acid secretion. Intrinsic factor is needed for the absorption of vitamin B₁₂ in the terminal ileum. Although this effect remains controversial, monitoring vitamin B₁₂ levels periodically or looking for signs of B₁₂ deficiency on complete blood counts (eg, elevated mean corpuscular volume, abnormal red cell morphology, etc) may be prudent with patients receiving long-term PPI therapy.^3,36

Recently, some researchers have suggested that long-term PPI use may be associated with an increased frequency of fractures. At this point, such an association is only suggested, far from persuasively demonstrated. A second issue regarding long-term acid suppression by PPIs or H₂ blockers is a possible increase in the frequency of community-acquired pneumonia. Although there are data suggesting an association, it has not been shown in a randomized controlled trial. Potential risk of fractures and pneumonia must be weighed against the known benefits of acid suppression for appropriate indications.

Another important concern with long-term PPI use has been the development of gastric carcinoid tumors caused by hypersecretion of gastrin. The physiologic basis for this effect is that the normal feedback mechanism to decrease the secretion of gastrin is the low pH of the gastric lumen. By markedly inhibiting the production of acid, PPIs remove the negative feedback mechanism, resulting in promoting the release of gastrin. Gastrin, in turn, has the theoretical potential to stimulate the development of carcinoid tumors. Yet, there have been no reports of gastric carcinoid tumors in patients without an underlying predisposing syndrome.³

The pharmacist's role in the management of patients with GERD is multifaceted. When patients choose to treat their symptoms with OTC agents, it is important that the pharmacist discuss their symptoms with them to determine the appropriateness of OTC

pumps in the parietal cell are inhibited. After a meal, the window of opportunity is ~90 minutes, which is approximately the same as the half-life of most PPIs in the elderly. The prolonged duration of action of PPIs is due to the irreversible inhibition of proton pumps by PPIs. If taking the medication up to 30 minutes before or within 90 minutes after a meal is not practical, a reasonable compromise might be to take the agent at the beginning of a meal. Some data suggest that taking PPIs before breakfast provides maximal efficacy, although in cases where higher dosages are needed, divided doses seem to be more efficacious.³⁷ Pharmacists may include these recommendations when counseling patients regarding the use of PPIs so as to promote the maximal efficacy of the prescribed agent.

Alternative routes of administration may be needed in elderly patients due to difficulty in swallowing, intolerance of capsule or tablet formulations, or the use of feeding tubes. Both lansoprazole and omeprazole capsules can be opened and the granules taken with water, a bicarbonate-based suspension, or apple or orange juice, or the granules may be sprinkled on applesauce or yogurt.³⁹ Additionally, lansoprazole is available as a dissolvable tablet (Prevacid Solutab) for oral or nasogastric tube administration.

Conclusion

GERD is a common disease in both young and elderly patients. GERD can interfere markedly with patients' QOL. In addition, it entails a substantial economic burden related to the direct costs of diagnosis and treatment as well as the indirect costs related toabsenteeism and decreased productivity. Elderly patients more often have atypical symptoms and present with more severe disease, and not uncommonly with complications. Consequently, it is important that health care professionals remain vigilant to detect GERD in this population.

A number of agents are available for the management of GERD, including antacids, promotility agents, H₂ receptor antagonists, and PPIs. PPIs have been shown to be safe and effective in elderly patients with GERD and are associated with fewer side effects and interactions. Furthermore, their benefits have been shown to be sustainable for years. Consequently PPIs usually are the agents of choice for the management of GERD in young and elderly patients. Pharmacists have an important role in the identification of patients who need further evaluation and in the selection of therapy, as well as in monitoring efficacy, interactions, and side effects.

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