Gastro-oesophageal reflux disease (GORD) is a condition in which reflux of stomach contents into the oesophagus results in adverse symptoms. It is one of the most common gastrointestinal conditions in Australia and may result in significant morbidity. It occurs in 10% to 15% of the population, with obesity being a common risk factor. Other risk factors include advanced age, male gender, Caucasian ethnicity, smoking, and diets high in fats, sugars and salt.
A diagnosis of GORD can be made based on typical symptoms of heartburn and regurgitation. If there are no features of serious disease, suspected GORD can be managed with a trial of a proton pump inhibitor (PPI) for four to eight weeks. PPIs should be taken 30 to 60 minutes before food for optimal effect as they have a short plasma half-life (usually one to two hours), and are only effective in the postprandial period. If an increase in acid suppression is required, administration of a second dose is more effective than doubling a daily dose. Symptom relief appears to be equivalent across various PPIs. Individual differences in clinical response are largely related to adherence and dose timing. The PPI dose may also affect clinical response.
Once symptoms are controlled, step-down therapy may be attempted. The daily dose may be halved or administered on alternate days. If symptoms recur, sufferers should use the minimum dose that controls their symptoms. Another treatment option is to use PPIs only as required. However, antacids, and when required, H2-receptor antagonists are recommended as less potent alternatives to PPIs. Using a PPI when required should be adequate for some patients. However, 75% to 90% of patients will relapse within six months. This reflects the chronic nature of the condition rather than a failure of treatment.
Patients who have severe erosive esophagitis, scleroderma oesophagus, or Barrett’s oesophagus require long-term PPI treatment. If there is no response to PPI therapy, further investigation and a specialist referral are required.
It is important that lifestyle modification strategies be continued throughout the step-down process. Weight loss has the strongest evidence for efficacy. One study demonstrated an almost 40% decrease in the risk of frequent symptoms when body mass was reduced by 3.5kg/m2. Other strategies include restricting meal size, remaining upright after meals, and mostly drinking fluids between meals rather than with meals. If nocturnal symptoms are troublesome, patients may benefit from elevation of the head of the bed and avoidance of meals two to three hours before bedtime. While routine elimination of specific food groups is not recommended, patients should avoid foods that specifically trigger their symptoms. Cessation of tobacco and alcohol are also recommended, although case-control studies have not demonstrated an overall improvement in symptoms. Anticholinergic medications and medications that may cause chemical oesophagitis (e.g. oral bisphosphonates, doxycycline, and aspirin) may exacerbate reflux symptoms.
Adverse effects of PPIs include headache and diarrhoea (less than 2%). Interstitial nephritis, hypomagnesaemia, reduced vitamin B12 absorption, increased Clostridium difficile infection and possibly community-acquired pneumonia are other rare, however important, adverse effects. There is a pharmacokinetic and pharmacodynamic interaction between PPIs and thienopyridines such as clopidogrel. However, there is no evidence of an increased risk of cardiovascular events in patients taking this combination. There is also no evidence that separating the doses of PPI and thienopyridine changes cardiac risk. If there are concerns regarding this interaction, then rabeprazole may be preferred. Rabeprazole is a less potent inhibitor of cytochrome P450 and therefore less likely to result in drug interactions. There is an association between PPIs and osteoporotic fractures, which may be partly explained by reduced calcium absorption in the presence of altered gastric acidity. However, it may be due to shared risk factors such as increased age and medical comorbidity.
Approximately 20% to 30% of patients do not respond completely to PPI therapy and will have persistent symptoms. The first step is to review the diagnosis. Delayed gastric emptying, functional dyspepsia and functional heartburn are commonly confused with GORD. Non-adherence or inappropriate dosing should also be considered when patients experience a suboptimal response. Adherence to PPIs is often poor and has been reported to be 46% to 55% in patients with persistent symptoms. There is also a poor understanding of the pharmacokinetics of PPIs with nearly 70% of general practitioners, and 20% of gastroenterologists, incorrectly instructing patients about when to take doses. For maximum efficacy, it is recommended that PPIs be administered before a meal. If greater acid suppression is still considered necessary, the dose may be increased to twice daily dosing, or a different PPI may be trialled. The addition of a night time H2-receptor antagonist (although tachyphylaxis may develop within two to six weeks), or a mucosal protectant may also be considered. However, there is limited evidence to support the use of sucralfate, a mucosal protectant, in the treatment of GORD.
Surgery may be considered for patients who are unresponsive or intolerant to therapy. Laparoscopic fundoplication is the most common anti-reflux procedure performed and is highly effective in well-selected patients. However, it is only indicated for patients with refractory symptoms despite maximal medical management, patients intolerant of treatment, and those with serious complications.
Patients often try over-the-counter medicines such as antacids or H2-receptor antagonists before they visit a doctor. If these treatments are effective, they may be continued, with the addition of lifestyle modifications. If symptoms persist and interfere with quality of life, a trial of PPI is appropriate due to PPIs being more potent acid suppressors than H2-receptor antagonists. A trial of PPI is useful, cost effective, and helpful in predicting which patients will respond to therapy. Treatment should continue for four to eight weeks. A negative trial does not exclude GORD as a diagnosis. However, it does reduce its likelihood and should prompt consideration of alternative diagnoses.
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