Laparoscopic Surgery, PPIs Both Effective for Chronic GERD

Laurie Barclay, MD

May 25, 2011

May 25, 2011 — Esomeprazole therapy vs standardized laparoscopic antireflux surgery (LARS) are each effective in achieving and maintaining remission at 5 years in patients with gastroesophageal reflux disease (GERD), according to the results of the Long-Term Usage of Esomeprazole vs Surgery for Treatment of Chronic GERD (LOTUS) multicenter clinical trial reported in the May 18 issue of the Journal of the American Medical Association.

"...GERD is a chronic, relapsing disease with symptoms that have negative effects on daily life," write Jean-Paul Galmiche, MD, from the Department of Gastroenterology and Hepatology, Nantes University, and Centre d'Investigation Clinique INSERM, Nantes, France, and colleagues from the LOTUS Trial Collaborators. "Two treatment options are long-term medication or surgery."

Study Results

Between October 2001 and April 2009, the LOTUS trial was conducted in academic hospitals in 11 European countries. The goal of this 5-year exploratory, randomized, open, parallel-group trial was to compare optimized esomeprazole therapy (20 - 40 mg/day, allowing for dose adjustments; n = 266) vs standardized LARS (n = 288) in patients with well-established chronic GERD who initially responded to acid suppression.

Of the 288 patients assigned to undergo LARS, 248 actually underwent the operation. Of 372 patients who completed 5-year follow-up, 192 were randomly assigned to receive esomeprazole and 180 patients were randomly assigned to undergo LARS. The main study endpoint was time to treatment failure, defined as the need for acid-suppressive therapy after LARS, and as inadequate symptom control after dose adjustment for esomeprazole. Time to treatment failure was expressed as estimated remission rates and analyzed with the Kaplan-Meier method.

At 5 years, estimated remission rates were 92% (95% confidence interval [CI], 89% - 96%) in the esomeprazole group vs 85% (95% CI, 81% - 90%) in the LARS group (log-rank P = .048). By use of best-case scenario modeling of the impact of study dropout, the between-group difference was no longer statistically significant.

At 5 years, symptom prevalence and severity in the esomeprazole and LARS groups, respectively, were 16% and 8% for heartburn (P = .14), 13% and 2% for acid regurgitation (P < .001), 5% and 11% for dysphagia (P < .001), 28% and 40% for bloating (P < .001), and 40% and 57% for flatulence (P < .001).

During the study, there were only 4 deaths in the esomeprazole group and 1 death in the LARS group, and none of these were attributed to treatment. Both groups had similar percentages of patients reporting serious adverse events (24.1% for esomeprazole and 28.6% for LARS).

"This paper, besides providing scientific data regarding the efficacy of esomeprazole in symptom control of PPI-responsive patients at 5 years follow-up, also provides clear evidence about the efficacy of LARS in the treatment of GERD," Toygar Toydemir, MD, general surgeon, and M. Ali Yerdel, MD, general surgeon and professor of surgery, both at İstanbul Surgery Hospital Reflux Diagnostic and Treatment Center in İstanbul, Turkey, told Medscape Medical News in an independent comment.

Interpret Study Findings With Caution

The commentators further stated that "There seems to be no statistical differences between the treatment groups at the termination of the study regarding the success of both methods. Nevertheless, all patients in the esomeprazole group who were regarded as treatment success have to continue their medication in even higher doses and for an indefinite amount of time, most probably lifelong, so new adverse effects of continuing lifelong medication are yet to develop."

"Surgical success, however, has the potential to spare the patients from lifelong medication and its costs and side effects," Drs. Toydemir and Yerdel said. "Furthermore, proton pump inhibitors (PPIs) cannot prevent the reflux of gastric contents into the esophagus and therefore only relief of symptoms can be achieved, and a cure for GERD can never be anticipated, in contrast to that achieved in LARS. It is therefore that the results and clinical implications of the study in question must be interpreted very cautiously."

Study limitations noted by the study authors were lack of generalizability to patients whose condition initially is partially or completely refractory to PPI therapy, lack of operation in 14% of participants randomly selected to receive surgery, and design as an exploratory study rather than as a superiority or equivalence trial. In addition, Drs. Toydemir and Yerdel note that involvement of many surgeons at multiple centers may have hindered achievement of standardized surgical technique.

"Longer follow-up results will be of interest, especially for possible underdiagnosed side effects of PPI's," Drs. Toydemir and Yerdel conclude. "Drug related side effects will occur in the long term, in contrast to LARS-related complications, which always become evident in the very short term."

AstraZeneca Research and Development funded this study and employs 3 of the study authors. Some of the other study authors have disclosed various financial relationships with AstraZeneca, Janssen-Cilag, Given Imaging, Xenoport, Norgine, Mauna Kea Technology, Shire Movetis, Fujinon, Erbe, and/or Hitachi. Drs. Toydemir and Yerdel have disclosed no relevant financial relationships.

JAMA. 2011;305:1969-1977. Abstract

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