Peptic ulcer: NSAIDs: 40 mg omeprazole heals ulcers and erosions with the fewest adverse effects.

Clinical bottom line (level 1b)

  1. Patients with peptic ulcers or erosions from regular NSAIDs use were equally likely to have healed after eight weeks if they took omeprazole or misoprostol.
  2. Patients who took 20 mg omeprazole compared with misoprostol were less likely to discontinue therapy (NNT = 14 at 8 weeks) .
  3. Patients who took 40 mg omeprazole compared with misoprostol were less likely to have moderate to severe symptoms of dyspepsia (NNT = 20 at 8 weeks) and were less likely to discontinue therapy (NNT = 16 at 8 weeks) .
  4. Patients who took 40 mg omeprazole compared with 20 mg were less likely to have moderate to severe symptoms of dyspepsia (NNT = 20 at 8 weeks) . There was no clear difference in the numbers who stop therapy.
Hawkey et al: New England Journal of Medicine 1998; 338: 727-734
Expires January 2003

The study

Double-blinded ?concealed randomised trial without intention-to-treat
Setting: 93 hospitals, Europe, Australia and North America

935 patients (aged 20 to 85; mean 58, 63% female) with any condition requiring continuous treatment with oral or rectal NSAIDs (at least 50 mg diclofenac, 100 mg ketoprofen, 500 mg naproxen daily), and gastric or duodenal peptic ulcers or erosions on endoscopy.

Excluded if
  • aged <18, or >85
  • severe concurrent reflux esophagitis
  • clinically important upper GI bleeding
  • pyloric stenosis
  • history of gastric surgery
  • gastrointestinal disorders that might impair absorption of the study drugs
  • on steroids at a dose equivalent to > 10 mg prednisolone

Note:

  • All patients continued NSAID medication during the study.

Control Group: (n = , 298 analysed): misoprostol 200 microg qds
Experimental Group: (n = , 308 analysed): omeprazole 20 mg daily
Experimental Group: (n = , 315 analysed): omeprazole 40 mg daily

99% followed for 8 weeks
Outcome notes:
  • treatment success : fewer than 5 gastric or duodenal erosions, no ulcer n endoscopy: and only mild symptoms of dyspepsia omeprazole 20 mg v. misoprostol
  • treatment success : omeprazole 40 mg v. misoprostol
  • treatment success : omeprazole 40 mg v. omeprazole 20 mg

The evidence

omeprazole 20 mg v. misoprostol
Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
treatment success 8 weeks 212
(71.1%)		 233
(75.7%)		 6%
(-3% to 17%)		 4.51%
(-2.52% to 11.5%)		 22
(NNT = 9 to infinity;
NNH = 40 to infinity)
moderate to severe symptoms of dypepsia weeks 33
(11.1%)		 34
(11.0%)		 0%
(-57% to 57%)		 0.03%
(-4.96% to 5.03%)		 2700
(NNT = 20 to infinity;
NNH = 20 to infinity)
discontinuation of treatment weeks 51
(17.1%)		 31
(10.1%)		 41%
(11% to 61%)		 7.05%
(1.61% to 12.5%)		 14
(8 to 62)

omeprazole 40 mg v. misoprostol
Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
treatment success 8 weeks 212
(71.1%)		 315
(75.2%)		 6%
(-4% to 16%)		 4.10%
(-2.92% to 11.1%)		 24
(NNT = 9 to infinity;
NNH = 34 to infinity)
moderate to severe symptoms of dyspepsia weeks 33
(11.1%)		 19
(6.0%)		 46%
(6% to 68%)		 5.04%
(0.61% to 9.47%)		 20
(11 to 160)
discontinuation of medication weeks 51
(17.1%)		 34
(10.8%)		 37%
(6% to 58%)		 6.32%
(0.84% to 11.8%)		 16
(8 to 120)

omeprazole 40 mg v. omeprazole 20 mg
Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
treatment success 8 weeks 233
(75.7%)		 237
(75.2%)		 -1%
(-9% to 9%)		 -0.41%
(-7.17% to 6.35%)		 -240
(NNT = 16 to infinity;
NNH = 14 to infinity)
moderate to severe symptoms of dypepsia 8 weeks 34
(11.0%)		 19
(6.03%)		 45%
(6% to 68%)		 5.01%
(0.63% to 9.38%)		 20
(11 to 160)
discontinuation of treatment 8 weeks 31
(10.1%)		 34
(10.8%)		 -7%
(-70% to 32%)		 -0.73%
(-5.53% to 4.07%)		 -140
(NNT = 25 to infinity;
NNH = 18 to infinity)

Comments

  1. Misoprostol is significantly cheaper than omeprazole
  2. Study results may need reviewing as new information concerning COX-2 specific NSAIDs emerge

Citation

  1. Hawkey CJ, Karrasch JA, Szczepanski L, et al: omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. New England Journal of Medicine 1998; 338: 727-734
Contributor: Sharon Straus and Chris Ball, October 1999
Reviewer: Ali Taha

Clinical Question.
Patient NSAID use with peptic ulcers or erosions
Intervention or Exposure omeprazole 40 mg or 20 mg
Comparison misoprostol
Outcome healing of ulcers or erosions