What is the best pharmacologic approach to managing moderate to severe heartburn?

Journal of Family Practice, Oct, 2001 by Sarah T. Melton, Angela Cimmino

Howden CW, Henning JM, Huang B, et al. Management of heartburn in a large randomized community-based study: comparison of four therapeutic strategies. Am J Gastroenterol 2001; 96:1704-10.

* BACKGROUND Heartburn is the most common symptom of gastroesophageal reflux disease (GERD). This study compared 4 pharmacologic strategies using the proton pump inhibitor (PPI) lansoprazole (Prevacid) and the [H.sub.2]-receptor antagonist ranitidine (Zantac) in the treatment of moderate to severe heartburn.

* POPULATION STUDIED This study included 593 men and women older than 18 years who experienced heartburn on at least 50% of days during a 7- to 10-day screening period, including at least one moderate to severe episode. Patients were excluded if they had coexisting systemic disease affecting the esophagus, active gastrointestinal bleeding, Zollinger-Ellison syndrome, esophageal varices, significant disease of major organs, abnormal laboratory values, current alcohol or illegal drug use, use of a PPI in the previous 3 months, or use of anticholinergic or prokinetic drugs during the screening period.

* STUDY DESIGN AND VALIDITY This was a double-blind controlled multicenter trial in which patients were randomized to 1 of 4 treatment groups. The subjects received one of the following: (1) lansoprazole 30 mg daily for 20 weeks; (2) ranitidine 150 mg twice daily for 20 weeks; (3) step-down therapy consisting of lansoprazole 30 mg daily for 8 weeks followed by ranitidine 150 mg twice a day for 12 weeks; or (4) a step-up approach of ranitidine 150 mg twice daily for 8 weeks followed by lansoprazole 30 mg once daily for 12 weeks.

The strengths of the study include the large sample size, power, and sound methodology. Allocation was appropriately concealed throughout the study. Heartburn associated with GERD is a chronic condition, and limiting the study to a 20-week period may have been too short to address efficacy differences in treatment regimens over the long term. Although PPI use in the recent past was specifically excluded, no mention is made regarding recent use of [H.sub.2]-receptor antagonists. A selection bias could be introduced if many of the patients in the study had unsuccessfully treated their symptoms with nonprescription [H.sub.2]-receptor antagonists. The manufacturer of lansoprazole sponsored this study.

* OUTCOMES MEASURED Two outcome measurements were reported, including the median severity of heartburn using a scale of 0 (no heartburn), 1 (mild heartburn), 2 (moderate heartburn), or 3 (severe heartburn) and the percentage of 24-hour heartburn-free days. Outcomes measurements were based on self-report in daily diaries. Antacid use was also reported.

* RESULTS All patients, regardless of treatment, reported a marked clinically relevant decline in the intensity of their heartburn symptoms. The median heartburn severity decreased from 1.88 to 0.46 in the ranitidine group, from 1.75 to 0.25 in the lansoprazole group, from 1.75 to 0.35 in the step-up group, and from 1.70 to 0.44 in the step-down group (P [is less than] .05 for lansoprazole vs the other groups). The lansoprazole group also had a significantly higher percentage of 24-hour heartburn-free days (median=81.4%; P [is less than] .01) than the ranitidine (66.6%), step-up (66.9%), and step-down (73.6%) groups. In the step-up and step-down groups, heartburn was less severe, and percentages of 24-hour heartburn-free days were higher during lansoprazole treatment regardless of treatment sequence (P [is less than] .001). Over the 20 weeks of treatment, antacid use was required on a significantly higher percentage of days in the ranitidine (median=18.7%; P [is less than] .001), step-up (12.3%; P [is less than] .05), and step-down (18.5%; P [is less than] .001) groups than in the lansoprazole group (8.6%).

RECOMMENDATIONS FOR CLINICAL PRACTICE

Most patients with moderate to severe heartburn will experience relief with either [H.sub.2]-receptor antagonist or PPI therapy. Results in this study were better when patients started and stayed on regular doses of lansoprazole. Heartburn severity was also less with lansoprazole but minimally different. This study did not address cost issues, although a recent study in primary care patients with heartburn symptoms found that omeprazole (Prilosec) provided greater resolution of symptoms than ranitidine, with no significant differences in total outpatient costs between the groups.[1] Although step-down and step-up therapies are often recommended to decrease total costs, they were less effective than continuous-dose therapy in this study.

Sarah T. Melton, PharmD, BCPP
Highlands Family Medicine
Lebanon, Virginia
E-mail: stmelton@cablenet-va.com
and
Angela Cimmino, PharmD, BCPS
Medical College of Virginia
Richmond
E-mail: acimmino@hsc.vcu.edu

REFERENCE

[1.] Kaplan-Michlis B, Spiegler GE, Zodet MW, et al. Effectiveness and costs of omeprazole vs ranitidine for treatment of symptomatic gastroesophageal reflux disease in primary care clinics in West Virginia. Arch Fam Med 2000; 9:624-30.