Sixteen studies were included (n at least 13,374): 9 RCTs (n=5,771) and 7 observational studies (n at least 7,603).
In terms of study quality, the Jadad scores ranged from 1 to 5 points. Four RCTs scored 4 or more points. Five of the 9 RCTs failed to report an adequate method of randomisation and were only awarded one out of a possible 2 points for this criterion.
Intermittent PPI treatment. One RCT (704 patients with EE or ENRD) reported that one year of intermittent treatment (2- to 4-week courses) was successfully completed in 48% allocated to omeprazole 20 mg, 46% allocated to omeprazole 10 mg and 47% allocated to ranitidine. Patients experienced between 273 and 279 days in 12 months off treatment with PPI or H2-receptor antagonist.
On-demand PPI treatment.
One RCT (421 patients with GERD but without EE) reported that the percentage of patients willing to continue their allocated regimen at 6 months was 83% for omeprazole 20 mg, 69% for omeprazole 10 mg (P<0.01 for 10 mg versus 20 mg) and 56% for placebo (P<0.001 versus 20 mg omeprazole and P<0.01 versus omeprazole 10 mg). Patients taking placebo consumed more antacid tablets.
One RCT (342 patients with GERD but without EE) reported a statistically significantly higher percentage of patients who had discontinued treatment by 6 months because of insufficient control of heartburn with placebo compared with esomeprazole 20 mg (52% versus 14%, P<0.0001). Patients taking placebo consumed significantly more antacid tablets.
One RCT (721 patients with ENRD) reported that the percentage of patients who discontinued their allocated regimen at 6 months was 11% for esomeprazole 40 mg, 8% for esomeprazole 20 mg and 42% for placebo. Significantly more patients taking esomeprazole were free from gastrointestinal symptoms at 6 months compared with placebo.
One RCT (100 patients with grade A or B endoscopically diagnosed EE entered; 66 patients whose symptoms resolved with initial treatment took on-demand treatment) reported similar levels of symptom control at 4 to 8 weeks between patients taking on-demand esomeprazole 40 mg or omeprazole 20 mg and those taking continual daily dosing. On-demand treatment with omeprazole 20 mg was superior to continuous treatment in controlling GERD symptoms.
One RCT (1,052 patients with GERD with EE or ENRD) reported that the percentage of patients 'quite satisfied' or 'completely satisfied' with their treatment by 6 months was 89.6% for continuous omeprazole 20 mg and 88.4% for esomeprazole 40 mg.
One RCT (418 patients with GERD) reported that the number of patients discontinuing their allocated regimen by 6 months was 16 out of 279 for rabeprazole 10 mg and 28 out of 137 for placebo (P<0.00001).
One RCT (1,471 patients with GERD) reported similar levels of patient satisfaction for on-demand esomeprazole 20 mg and intermittent esomeprazole 40 mg daily for 2 to 4 weeks.
Step-down from PPI to alternative treatment.
One RCT (593 patients with uninvestigated heartburn) reported that the highest percentage of heartburn-free periods were in patients receiving continuous lansoprazole 30 mg once daily for 20 weeks (82%). Corresponding rates were 66% for continuous ranitidine (150 mg twice daily for 20 weeks), 74% for 'step-up' from ranitidine 150 mg twice daily for 8 weeks followed by lansoprazole 30 mg daily for 12 weeks, and 67% for 'step-down' from lansoprazole 30 mg once daily for 8 weeks followed by ranitidine 150 mg twice daily for 12 weeks (P<0.01 for each comparison versus continuous lansoprazole).
Non-randomised studies reported that some patients with EE can achieve remission with PPI taken on alternate days or less often; the rates of remission on these reduced-dose regimens ranged from 26 to 79.5%.
Further details of these studies were reported in the review.