A Cochrane review included 8 studies with a total of 274 subjects. Additional bedtime H2RAs decreased the prevalence rate of nocturnal gastric acid breakthrough (RR 0.48, 95% CI 0.30 to 0.75, statistical heterogeneity I2=52%; 8 studies, n=274). Sub-group analyses showed that in short-term group additional bedtime H2RAs decreased the prevalence rate of nocturnal gastric acid breakthrough (RR 0.43, 95% CI 0.25 to 0.72, statistical heterogeneity I2=55%; 7 studies, n=254). In long-term group, additional bedtime H2RAs had no significant effect compared with control group (RR 0.75, 95% CI 0.41 to 1.36; 1 study, n=10).
The results of the analyses for secondary outcomes showed that additional bedtime H2RAs decreased the percentage of time during which pH is less than 4.0 inside the stomach (MD -10.41, 95% CI -12.51 to -8.30, statistical heterogeneity I2=50%; 2 studies, n=72) and promoted median intragastric pH (MD 1.22, 95% CI 0.78 to 1.65, statistical heterogeneity I2=83%; 3 studies, n=116).
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment and lack of blinding), by inconsistency (variability in results across studies), and by indirectness (lack of long term studies).