Assessment of Treatment Options to Prevent Recurrent Reflex Esophagitis

Michael Blocker

7/26/96

Case #1:
53 y.o. Black male with h/o cocaine use, s/p non Q wave MI 1 yr ago (by enzymes and chest pain), with subsequent cardiac catheterization showing no significant disease who presents to ER with chest pain without EKG changes and positive cocaine in the urine, and
ROS suggesting reflex symptoms. Course: admitted to telemetry and r/o'd for MI; UGI seriesshowed reflex disease. Sx relieved with omeprazole.

Case #2: 39 y.o. Black female with h/o GERD (rx'd with ranitidine), and severe asthma who presents to ER with severe reflex symptoms and subsequent asthma attack. Course: required albuterol 35mg over 4 hour period and admission secondary to poor peak flows and hypokalemia.

Assumption: Both admissions were secondary to recurrent GERD.

Clinical Question: What is the most efficacious medication regimen to prevent recurrent reflux esophagitis?

Data: (from Vigneri, S et. al., NEJM, 1995, 333:1106-1110)

Treatment Group Grade 1 Grade2 Grade3 vs. omeprazole vs. omeprazole/
cisapride
  # of patients (%) with recurrence    
ciapride (n=35)          
endoscopic signs 3 (20) 4 (27) 5 (100) p=0.2 p=0.003
symptoms 2 (13) 5 (40) 5 (100) p<0.001 p<0.001
ranitidine (n=35)          
endoscopic signs 4 (27) 4 (27) 5 (100) p=0.003 p<0.001
symptoms 4 (27) 5 (33) 5 (100) p<0.001 p<0.001
omeprazole (n=35)          
endoscopic signs 0 2 (13) 3 (60) n/a ns
symptoms 0 0 1(20) n/a ns
ranitidine/cisapride (n=35)          
endoscopic signs 1 (7) 3 (20) 4 (80) ns p=0.003
symptoms 2 (13) 1 (7) 3 (60) ns ns
meprazole/cisapride (n=35)          
endoscopic signs 0 0 3 (60) ns n/a
symptoms 0 0 0 ns n/a

1. Univariate analysis showed relapse was assoc. with higher frequency of grade 3 esophagitis (49%, p<0.001) and EtOH intake (54%, p<0.001).

2. Independent risk factors for relapse were found to be only grade of esophagitis (p<0.001) and maintenance therapy (p<0.001).

3. When all treatment groups were combined, risk of relapse (endoscopically) was 22.6 times higher for patients with symptoms vs without (95% CI = 7.3-69.9).

4. Side effects of treatment occurred in 28 (16%) of patients. 5 patients withdrew from the study secondary to side effects. All side effects resolved spontaneously or after withdrawal of medication.

5. At the end of the healing phase, all groups had similar elevation in gastric levels. After treatment, only the cisapride group had significantly decreased gastrin levels (p<0.001).

Conclusions:
1. Omeprazole and omeprazole/cisapride treatment is more effective than cisapride or
ranitidine alone at preventing recurrent GERD

2. Cisapride/ranitadine treatment is more effective than ranitidine alone, but not cisapride alone, at preventing recurrent GERD (data not shown)

3. Financial constraints and patient compliance with multi-drug regimens need to be considered in choosing treatment regimen .

4. Use of ranitidine alone was not supported by this study, as there was no direct comparison with placebo