Department of Gastroenterology and Hepatology, Nantes University, CIC INSERM, Place Alexis Ricordeau, 44093 Nantes, France.
JAMA. 2011 May 18;305(19):1969-77. doi: 10.1001/jama.2011.626.
Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease with symptoms that have negative effects on daily life. Two treatment options are long-term medication or surgery.
To evaluate optimized esomeprazole therapy vs standardized laparoscopic antireflux surgery (LARS) in patients with GERD.
DESIGN, SETTING, AND PARTICIPANTS: The LOTUS trial, a 5-year exploratory randomized, open, parallel-group trial conducted in academic hospitals in 11 European countries between October 2001 and April 2009 among 554 patients with well-established chronic GERD who initially responded to acid suppression. A total of 372 patients (esomeprazole, n = 192; LARS, n = 180) completed 5-year follow-up. Interventions Two hundred sixty-six patients were randomly assigned to receive esomeprazole, 20 to 40 mg/d, allowing for dose adjustments; 288 were randomly assigned to undergo LARS, of whom 248 actually underwent the operation.
Time to treatment failure (for LARS, defined as need for acid suppressive therapy; for esomeprazole, inadequate symptom control after dose adjustment), expressed as estimated remission rates and analyzed using the Kaplan-Meier method.
Estimated remission rates at 5 years were 92% (95% confidence interval [CI], 89%-96%) in the esomeprazole group and 85% (95% CI, 81%-90%) in the LARS group (log-rank P = .048). The difference between groups was no longer statistically significant following best-case scenario modeling of the effects of study dropout. The prevalence and severity of symptoms at 5 years 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). Mortality during the study was low (4 deaths in the esomeprazole group and 1 death in the LARS group) and not attributed to treatment, and the percentages of patients reporting serious adverse events were similar in the esomeprazole group (24.1%) and in the LARS group (28.6%).
This multicenter clinical trial demonstrated that with contemporary antireflux therapy for GERD, either by drug-induced acid suppression with esomeprazole or by LARS, most patients achieve and remain in remission at 5 years.
clinicaltrials.gov Identifier: NCT00251927.
胃食管反流病（GERD）是一种慢性、复发性疾病，其症状对日常生活有负面影响。两种治疗选择是长期药物治疗或手术。
评估优化的埃索美拉唑治疗与标准化腹腔镜抗反流手术（LARS）在 GERD 患者中的疗效。
设计、地点和参与者：LOTUS 试验是一项为期 5 年的探索性随机、开放、平行组试验，于 2001 年 10 月至 2009 年 4 月在 11 个欧洲国家的学术医院进行，纳入了 554 例经酸抑制治疗后症状缓解的慢性 GERD 患者。共有 372 例患者（埃索美拉唑组 n = 192；LARS 组 n = 180）完成了 5 年随访。
266 例患者随机接受埃索美拉唑治疗，剂量为 20 至 40mg/d，并可调整剂量；288 例患者随机接受 LARS 治疗，其中 248 例实际接受了手术。
治疗失败时间（对于 LARS，定义为需要酸抑制治疗；对于埃索美拉唑，剂量调整后症状控制不足），以估计缓解率表示，并采用 Kaplan-Meier 法进行分析。
埃索美拉唑组 5 年估计缓解率为 92%（95%置信区间 [CI]，89%-96%），LARS 组为 85%（95% CI，81%-90%）（对数秩检验 P =.048）。在对研究退出影响进行最佳情况情景建模后，两组之间的差异不再具有统计学意义。埃索美拉唑组和 LARS 组 5 年时的症状发生率和严重程度分别为：烧心 16%和 8%（P =.14）、反酸 13%和 2%（P <.001）、吞咽困难 5%和 11%（P <.001）、腹胀 28%和 40%（P <.001）、呃逆 40%和 57%（P <.001）。研究期间死亡率较低（埃索美拉唑组 4 例死亡，LARS 组 1 例死亡），且与治疗无关，埃索美拉唑组（24.1%）和 LARS 组（28.6%）报告严重不良事件的患者百分比相似。
这项多中心临床试验表明，对于 GERD 的当代抗反流治疗，无论是通过埃索美拉唑诱导的酸抑制药物治疗还是 LARS，大多数患者在 5 年内都能达到并保持缓解。
clinicaltrials.gov 标识符：NCT00251927。
