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Meta-Analysis
. 2017 Jan 19;7:41021.
doi: 10.1038/srep41021.

Effectiveness and Tolerability of Different Recommended Doses of PPIs and H 2 RAs in GERD: Network Meta-Analysis and GRADE System

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Free PMC article
Meta-Analysis

Effectiveness and Tolerability of Different Recommended Doses of PPIs and H 2 RAs in GERD: Network Meta-Analysis and GRADE System

Chao Zhang et al. Sci Rep. .
Free PMC article

Abstract

Proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are used for gastro-esophageal reflux disease (GERD); however, the clinical evidence for treatment is poor. We evaluated the effectiveness and tolerability of different doses of PPIs, H2RAs and placebo in adults with GERD. Six online databases were searched through September 1, 2016. All related articles were included and combined with a Bayesian network meta-analysis from randomized controlled trials (RCTs). The GRADE systems were employed to assess the main outcome. Ninety-eight RCTs were identified, which included 45,964 participants. Our analysis indicated that the full/standard dose of esomeprazole at 40 mg per day was the most efficient in healing among nine different dosages of PPIs and H2RAs. The main efficacy outcome did not change after adjustments for the area, age, level of disease from endoscopy, year of publication, pharmaceutical industry sponsorship, Intention-to-treat (ITT)/per-protocol (PP), withdrawal rate, pre-set select design bias, single blinded and unblinded studies, study origination in China, study arms that included zero events, inconsistency node or discontinued drug were accounted for in the meta-regressions and sensitivity analyses. This research suggests that the full/standard doses (40 mg per day) of esomeprazole should be recommended as first-line treatments for GERD in adults for short-term therapy.

Figures

Figure 1
Figure 1. Summary of trial identification and selection.
Figure 2
Figure 2. Network figure for healing.
(The node sizes correspond to the number of trials that investigated the treatments. Directly comparable treatments are linked with a line, and the thickness of the line corresponds to the sample size in each pairwise treatment comparison. The “References” at the upper right corner displays three different nodes sizes correspond to three different levels of sample size of placebo and active drugs, three different lines thickness correspond to the three levels of different sample size of each pairwise treatment comparison).
Figure 3
Figure 3. Network figure for relief of symptoms.
(The node sizes correspond to the number of trials that investigated the treatments. Directly comparable treatments are linked with a line, and the thickness of the line corresponds to the sample size in each pairwise treatment comparison. The “References” at the upper right corner displays three different nodes sizes correspond to three different levels of sample size of placebo and active drugs, three different lines thickness correspond to the three levels of different sample size of each pairwise treatment comparison).
Figure 4
Figure 4. Network figure for tolerance.
(The node sizes correspond to the number of trials that investigated the treatments. Directly comparable treatments are linked with a line, and the thickness of the line corresponds to the sample size in each pairwise treatment comparison. The “References” at the upper right corner displays three different nodes sizes correspond to three different levels of sample size of placebo and active drugs, three different lines thickness correspond to the three levels of different sample size of each pairwise treatment comparison).
Figure 5
Figure 5. Effects of active drugs with different recommended doses and the overall effects from PPI and H2RA families compared with placebo for healing.
Figure 6
Figure 6. Effects of active drugs with different recommended doses and the overall effects from PPI and H2RA families compared with placebo for the relief of symptoms.
Figure 7
Figure 7. Effects of active drugs with different recommended doses and the overall effects from PPI and H2RA families compared with placebo for tolerance.
Figure 8
Figure 8. Ranking of all treatment drugs for healing, relief of symptoms, and tolerance outcomes.
(All drug treatments were ranked according to their surface under the cumulative ranking (SUCRA) values. In ranking order for healing rates, from best to worst, the higher SUCRA scores demonstrate better effects. The red line indicates healing. In a similar manner, the green line indicates the relief of symptoms, and the blue line indicates tolerance. Eso20: esomeprazole at 20 mg per day, Eso40: esomeprazole at 40 mg per day, Lan15: lansoprazole at 15 mg per day, Lan30: lansoprazole at 30 mg per day, Lan60: lansoprazole at 60 mg per day, Ome10: omeprazole at 10 mg per day, Ome20: omeprazole at 20 mg per day, Ome40: omeprazole at 40 mg per day, Pan10–20: pantoprazole at 10–20 mg per day, Pan40: pantoprazole at 40 mg per day, Pan80: pantoprazole at 80 mg per day, Rab5–10: rabeprazole at 5–10 mg per day, Rab20: rabeprazole at 20 mg per day, Rab40–50: rabeprazole at 40–50 mg per day, Cim200–400: cimetidine at 200–400 mg per day, Cim600–800: cimetidine at 600–800 mg per day, Cim1600: cimetidine at 1600 mg per day, Fam20: famotidine at 20 mg per day, Fam40: famotidine at 40 mg per day, Fam80: famotidine at 80 mg per day, Niz150: nizatidine at 150 mg per day, Niz300: nizatidine at 300 mg per day, Niz600: nizatidine at 600 mg per day, Ran ≤300: ranitidine at ≤300 mg per day, Ran600: ranitidine at 600 mg per day, Ran1200: ranitidine at 1200 mg per day).

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