Heartburn-dominant, uninvestigated dyspepsia:: a comparison of 'PPI-start' and 'H2-RA-start' management strategies in primary care -: the CADET-HR Study

Background: There are few data on empiric, stepped therapy for heartburn relief or subsequent relapse in primary care. Aims: To compare heartburn relief produced by a proton pump inhibitor-start or an H-2-receptor antagonist-start with step-up therapy, as needed, followed by a treatment-free period to assess relapse. Methods: Heartburn-dominant uninvestigated dyspepsia patients from 46 primary care centres were randomized to one of two active treatment strategies: omeprazole 20 mg daily (proton pump inhibitor-start) or ranitidine 150 mg bid (H-2-receptor antagonist-start) for the first 4-8 weeks, stepping up to omeprazole 40 or 20 mg daily, respectively, for 4-8 weeks for persistent symptoms. Daily diaries documented heartburn relief (score <= 3/7 on <= 1 of 7 prior days) and relapse (score >= 4 on >= 2 of 7 prior days). Results: For 'proton pump inhibitor-start' (n = 196) vs. 'H-2-receptor antagonist-start' (n = 194), respectively, heartburn relief occurred in 55.1% vs. 27.3% (P < 0.001) at 4 weeks and in 88.3% vs. 87.1% at 16 weeks. After therapy, 308 patients were heartburn-free (159 vs. 149); median times to relapse were 8 vs. 9 days and cumulative relapse rates were 78.6% vs. 75.8%, respectively. Conclusions: An empiric 'proton pump inhibitor-start' strategy relieves heartburn more effectively than an 'H-2-receptor antagonist-start' strategy up to 12 weeks but has no effect on subsequent relapse, which is rapid in most patients.