Clinical effectiveness and quality of life with ranitidine vs placebo in gastroesophageal reflux disease patients: a Clinical Experience Network study - CEN

Journal of Family Practice, August, 1995 by David R. Rush, W. Jack Stelmach, Terri L. Young, Leonard J. Kirchdoerfer, Jane Scott-Lennox, Harmon E. Holverson, Seymour M. Sabesin, Thomas A. Nichols

Background. Gastroesophageal reflux disease (GERD), often characterized as heartburn, is a highly common presenting complaint to family physicians. This study is the first large, prospective, nationwide family practice outpatient evaluation of the effectiveness of the histamine ([H.sub.2])-receptor antagonist ranitidine as medical therapy for this disorder.

Methods. This randomized, double-blind, placebo-controlled, parallel group, 6-week study was designed to evaluate the effect of ranitidine on clinical outcomes and quality of life in patients with GERD. Eligible patients included those who were at least 18 years old and had at least a 3-month history of heartburn or heartburn therapy and a minimum of 4 days with at least one heartburn episode in the week preceding the baseline visit. Quality-of-life effects were measured using a general health status instrument and a previously validated heartburn-specific questionnaire.

Results. Ranitidine treatment conferred clinically and statistically significant reductions in mean heartburn pain scores within the first 24 hours (P[less than or equal to].001) and mean number of heartburn episodes within the first 48 hours (P[less than or equal to].001). These reductions were maintained throughout the 6-week trial, during both daytime and nighttime. Compared with patients receiving placebo, patients treated with ranitidine also used significantly fewer doses of antacids (P[less than or equal to].003). Further, both ranitidine-treated patients' and their physicians' global assessments of decreases in heartburn severity, as well as clinical improvement on ranitidine, proved superior to those of controls (P<.001). The rate of adverse events associated with ranitidine and placebo was low and similar.

Ranitidine-treated patients had more favorable scores on the general health status dimensions of physical functioning, bodily pain, and vitality (P<.05), and more favorable scores on all dimensions of the heartburn-specific questionnaire (P<.05).

Conclusions. Twice-daily treatment with ranitidine 150 mg is a valuable therapy for GERD in a typical family practice setting. It reduces the frequency and severity of symptoms within the first 24 to 48 hours of treatment and diminishes the use of nonprescription antacids while improving the quality of life as measured by both a general health status instrument and a disease-specific instrument.

Key words. Gastroesophageal reflux; heartburn; treatment outcome; quality of life; ranitidine. (J Fam Pract 1995; 41:126-136)

Gastroesophageal reflux disease (GERD) ranks among the most prevalent clinical conditions affecting the upper gastrointestinal (GI) tract. The most specific and frequent symptom in patients with reflux disease is heartburn. A cross-sectional survey by the Gallup Organization(1) determined that as many as 4 of 10 healthy US adults may suffer heartburn at least once a month. Some 7% to 10% experience heartburn daily.(1)(2)(3)

Although some commentators(4) have argued that GERD is difficult to diagnose, others(5) have reported that family physicians exhibit a concordance rate of 78% between initial diagnostic hypothesis and the conclusion reached after 3 months of follow-up for dyspepsia. A decision-analysis model study(4) on GERD treatment strategies concluded that the clinical and economic outcomes achieved by empiric treatment were equivalent to those preceded by an initial diagnostic workup, ie, upper gastrointestinal series or endoscopy.

Various strategies for the treatment of GERD have been proposed. A multistep approach has been described(6) that entails lifestyle changes, over-the-counter (OTC) antacids, histamine ([H.sub.2])-receptor antagonists in varying doses, prokinetic agents (eg, metoclopramide), and acid (proton) pump inhibitors (eg, omeprazole) in an acutecare and maintenance algorithm. A proposal to prescribe proton-pump inhibition as initial therapy has been described(4) but without extended clinical follow-up data. For complicated GERD cases, surgery has proved more effective than medical therapy in improving symptoms and endoscopic signs of esophagitis for as long as 2 years; however, medical treatment has also been considered effective.(7)(8)

Depending on the frequency and duration of esophageal exposure to the acidic contents of the stomach, patients may experience mild to severe esophagitis and perhaps even relapse after acute treatment has allowed healing to occur. The recurrent nature of this disease in some patients may interfere with daily functioning. Therefore, it is important to assess not only the clinical impact of this disease, but also the impact of symptoms on the patient's daily life.

To date, there has been no large prospective study to assess the use of an [H.sub.2]-receptor antagonist among family practice outpatients diagnosed by clinical presentation rather than endoscopy. The Clinical Experience Network (CEN) undertook this study to evaluate ranitidine's clinical effectiveness in a randomized, placebo-controlled, double-blind trial designed to simulate ordinary family practice in the care of patients with mild to moderate GERD. This study also measured the impact of GERD treatment on quality of life, using a general and a disease-specific instrument within the clinical trial design.