Meta Analysis Of Therapeutic Effects In Patients With Gastroesophageal Reflux Disease By Maintenance And Intermittent Therapy Of Proton Pump Inhibitors

Objective:The gastroesophageal reflux disease?GERD?is a group of diseases which caused by the refluxing of stomach's contents into esophagus,leading to discomfort symptoms and/or complications.The main symptoms of patients with GERD are intraesophageal symptoms such as heartburn and regurgitation,and extraesophageal ones such as cough and asthma.Complications are supervene reflux esophagitis,esophageal ulcers,esophageal stenosis,upper gastrointestinal bleeding and Barrett's Esophagus?BE?.In the past three decades,it was reported that the morbidity of GERD was increasing annually.The annual incidence of GERD in the United States increased about4 percent.The incidence of Barrett's Esophagus and esophageal adenocarcinoma has increased 3-5 times over the past 25 years.Its complications Barrett's Esophagus belongs to precancerous lesions,and the rate development to esophageal adenocarcinoma is 30%more than the general population.Because GERD has a higher recurrence rate,long-term drug treatment is required,resulting in increased medical costs.At the same time,the disease has a huge impact on the patient's physical and mental as well as daily work and life.Therefore,the disease has become one of the world's refractory diseases.The pathogenesis of GERD is not fully elucidated.Inhibition of gastric acid secretion is the main treatment of the disease.However,H₂ receptors antagonist?H₂RA?has a low cure rate for GERD,a short duration of symptom relief,and a drug tolerance in most patients after4-6 weeks.Therefore,long-term efficacy with H₂RA is poor.At present,the proton pump inhibitors?PPIs?is the main treatment for this disease.The main reason is that PPIs has strong acid supression effect,longer symptoms remission time,less drug tolerance,longer-term effectiveness of treatment.Although the safety of long-term use of PPIs has been confirmed by a variety of studies,there are still some adverse reactions.Common adverse reactions of the drugs are headache,nausea,vomiting,abdominal pain,diarrhea,and so on,but generally do not need to stop using.However,long-term inhibition of gastric acid secretion can cause gastric polyps,causing high gastrinemia,ECL cell proliferation,osteoporosis and other side effects.There are about 75%patient will relapse after discontinued antacids for 6 months,so it is needed for a long-term treatment.At present,GERD has three treatment options,maintenance therapy,intermittent therapy and on-demand treatment.At domestic and abroad,comparative analysis of GERD's maintenance and on-demand treatment suggests that on-demand treatment is only applicable to patients with NERD and unclassified mild GERD.It is not recommended for patients with severe reflux esophagitis.Moreover,on-demand treatment of GERD patients with poor symptoms control,high recurrence rate,and repeated inflammation will increase the risk of tissue malignant transformation.In this study,we further investigated the literature about long-term PPIs treatment for patients with GERD,and also compared with efficacy of maintenance treatment and intermittent treatment on GERD.Methods:Cochrane systematic review of evidence-based medicine methods were used in this study.Literatures of randomized controlled trials about GERD maintenance and intermittent therapy between library building and now were searched by using database including Pubmed,Embase,Chinese biomedical database,SCI?ISI?,ACS,METSTR,Whip biomedical journals library,Wanfang data library,China national knowledge,and so on.Subjects need to adopt random principles.The enrolled literatures are published in Chinese or English.The patients are adults and meet the 2007consensus diagnostic criteria and other relevant diagnostic criteria.Maintenance therapy was defined as the treatment group,and intermittent therapy was defined as the control group.The clinical symptoms of GERD patients and the cure rate of esophageal mucosal injury under electronic endoscopy were observed.Esophageal anatomical defects?such as esophageal hiatal hernia?,esophageal sphincter function loss which is not suitable for medical treatment of digestive diseases are excluded.Literatures which are related to traditional Chinese medicine treatment,endoscopic treatment and surgical treatment are also excluded.The related literatures are excluded if the full text and detailed data can not be obtained.The durations of the studies were 2 months to 18 months,with 10 cases to 200 cases.After reading the full text,there are fifteen articles enrolled in Meta analysis finally,thirteen Chinese literatures and two English literatures.We extracted twenty-two randomized controlled studies.Meta-analysis was performed using RevMan5.2 software.Results:Meta-analysis of the cure rate of clinical symptoms in GERD patients and the cure rate of esophageal mucosal lesions under endoscopy showed that there is no significant difference between two groups of PPIs intermittent treatment and maintenance treatment[RR=1.04,95%CL?0.99,1.10?,P=0.09>0.05,no significant difference,Funel plot without bias].The use of PPIs intermittent treatment are superior to the use of H₂RA maintenance treatment[RR=0.42,95%CL?0.34,0.52?,P<0.00001,significant difference,Funel plot without bias].And intermittent treatment of PPIs consumption,adverse reactions,side effects,medical expenses are less than maintenance therapy.Conclusions:According to meta-analysis results of GERD long-term drug treatment of maintenance treatment and intermittent treatment,the clinical symptoms cure rate and endoscopic esophageal mucosal injury healing rate in groups of PPIs intermittent treatment and the maintenance treatment has no significant difference.The use of PPIs intermittent treatment are superior to the use of H₂RA maintenance treatment.Due to intermittent treatment of drug consumption,adverse reactions,side effects,medical expenses are less than maintenance therapy,it is considered that proton pump inhibitor in the treatment of GERD with intermittent treatment is better than maintenance treatment.It is worthy of clinical application.There is one direction in the use of PPIs for small dose,long lasting,low adverse reactions by intermittent treatment for patients with GERD.