In current clinical practice, many patients with symptomatic GERD are treated empirically with medications without prior endoscopy, ie, without knowledge of whether the patient has erosive or nonerosive reflux disease. Empiric treatment with PPIs provides sustained symptomatic relief in 70–80% of patients, compared with 50–60% with H2 antagonists. Because of recent cost reductions, PPIs are used increasingly as first-line therapy for patients with symptomatic GERD. Due to recent safety concerns, however, initial empiric treatment with an H2 antagonist should be considered.
Sustained acid suppression with twice-daily PPIs for at least 3 months is used to treat extraesophageal complications of reflux disease (asthma, chronic cough, laryngitis, and noncardiac chest pain).
2. Peptic ulcer disease—Compared with H2 antagonists, PPIs afford more rapid symptom relief and faster ulcer healing for duodenal ulcers and, to a lesser extent, gastric ulcers. All the pump inhibitors heal more than 90% of duodenal ulcers within 4 weeks and a similar percentage of gastric ulcers within 6–8 weeks.
a.
H pylori-associated ulcers—For H pylori-associated ulcers, there are two therapeutic goals: to heal the ulcer and to eradicate the organism. The most effective regimens for H pylori eradication are combinations of two antibiotics and a PPI. PPIs promote eradication of H pylori through several mechanisms: direct antimicrobial properties (minor) and—by raising intragastric pH—lowering the minimal inhibitory concentrations of antibiotics against H pylori. Until recently, the most commonly recommended treatment regimen consisted of a 14-day regimen of “triple therapy”: a PPI twice daily; clarithromycin, 500 mg twice daily; and either amoxicillin, 1 g twice daily, or metronidazole, 500 mg twice daily. Due to increasing treatment failures attributable to rising clarithromycin resistance, “quadruple therapy” is now recommended as first-line treatment for patients who likely have clarithromycin resistance due to prior exposure or to residence in regions with high clarithromycin resistance. Two 14-day treatment regimens currently are recommended. Each includes a PPI twice daily with either: (a) bismuth subsalicylate 524 mg, metronidazole 500 mg, and tetracycline 500 mg, all given four times daily; or (b) amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily. After completion of antibiotic therapy, the PPI should be continued once daily for a total of 4–6 weeks to ensure complete ulcer healing.
b.
NSAID-associated ulcers—For patients with ulcers caused by aspirin or other NSAIDs, either H2 antagonists or PPIs provide rapid ulcer healing so long as the NSAID is discontinued; however, continued use of the NSAID impairs ulcer healing. In patients with NSAID-induced ulcers who require continued NSAID therapy, treatment with a PPI more reliably promotes ulcer healing.
Asymptomatic peptic ulceration develops in 10–20% of people taking frequent NSAIDs, and ulcer-related complications (bleeding, perforation) develop in 1–2% of persons per year. PPIs taken once daily are effective in reducing the incidence of ulcers and ulcer complications in patients taking aspirin or other NSAIDs.