Abstract and Introduction
Abstract
Objectives: High-quality data regarding the efficacy of acid-suppressive treatment for unexplained chest pain are lacking. The aim of this study was to evaluate the efficacy of esomeprazole in primary-care treatment of patients with unexplained chest pain stratified for frequency of reflux/regurgitation symptoms.
Methods: Patients with a ≥2-week history of unexplained chest pain (unrelated to gastroesophageal reflux) who had at least moderate pain on ≥2 of the last 7 days were stratified by heartburn/regurgitation frequency (≤1 day/week (stratum 1) vs. ≥2 days/week (stratum 2)) and randomized to 4 weeks of double-blind treatment with twice-daily esomeprazole 40 mg or placebo. Chest pain relief during the last 7 days of treatment (≤1 day with minimal symptoms assessed daily using a 7-point scale) was analyzed by stratum in keeping with the predetermined analysis plan.
Results: Overall, 599 patients (esomeprazole: 297, placebo: 302) were randomized. In stratum 1, more esomeprazole than placebo recipients achieved chest pain relief (38.7% vs. 25.5%; P=0.018); no between-treatment difference was observed in stratum 2 (27.2% vs. 24.2%; P=0.54). However, esomeprazole was superior to placebo in a post-hoc analysis of the whole study population (combined strata; 33.1% vs. 24.9%; P=0.035).
Conclusions: A 4-week course of high-dose esomeprazole provided statistically significant relief of unexplained chest pain in primary-care patients who experienced infrequent or no heartburn/regurgitation, but there was no such significant reduction in patients with more frequent reflux symptoms.
Introduction
Chest pain, often thought by patients to be cardiac in origin, is a significant driver of health-seeking behavior through visits to primary-care physicians or hospital emergency departments. Indeed, the incidence of a new diagnosis of chest pain was estimated at 15.5 per 1,000 person-years in the 1996 UK population. When assessing patients with chest pain, physicians must first consider underlying coronary artery disease and other serious reasons for chest pain. However, over 90% of patients presenting in primary care with chest pain have a noncardiac cause for their pain. Patients in whom cardiac causes have been ruled out can be classified as having noncardiac chest pain, but further clinical assessment is required to identify the underlying cause such as: gastrointestinal (e.g., gastroesophageal reflux disease (GERD)), pulmonary, musculoskeletal or psychiatric disorders. However, clinical assessment will often not reveal an organic or psychological cause of symptoms. When all logical diagnostic possibilities, including cardiac causes and GERD, have been excluded, the patient is said to have unexplained chest pain. Even if not life threatening, noncardiac and unexplained chest pain are associated with profound physical, psychological, and social consequences in the daily lives of the patients, and new treatment options are, therefore, required.
The results of two meta-analyses have suggested that acid-suppressive therapy with proton pump inhibitors (PPIs) can be used to identify GERD in patients with noncardiac chest pain, and that these agents are beneficial in relieving chest pain in such patients. However, most of the studies included in these meta-analyses were of a crossover design, had an inadequate sample size, and were conducted in a secondary or tertiary care setting. The meta-analyses suggested that larger, parallel-group design, high-quality trials are needed to more clearly elucidate the benefit of PPIs, particularly in the setting of primary care where most unexplained chest pain is managed. This study was, therefore, conducted to evaluate the efficacy, safety, and tolerability of esomeprazole for the treatment of unexplained chest pain in primary-care patients. We predicted that more patients with frequent concomitant symptoms of GERD (heartburn/regurgitation) would respond to esomeprazole therapy in terms of reduced chest pain than those with no or infrequent GERD symptoms. Patients were, therefore, stratified a priori into two strata based on the occurrence of concomitant GERD symptoms (average heartburn/regurgitation incidence on ≤1 day/week vs. ≥2 days/week).