Upper GI bleeding: rofecoxib reduced the risk compared with NSAIDs

Clinical bottom line (level 1b)

  1. Patients with osteoarthritis who took rofecoxib compared with NSAIDs were less likely to discontinue medication (NNT = 16 at 4 months) , have adverse GI effects (NNT = 78 at 4 months) , or suffer perforation, upper GI bleeding or symptomatic peptic ulcers (NNT = 103 at 4 months) .
  2. Patients on rofecoxib developed fewer gastroduodenal ulcers (NNT = 16 at 4 months) .
Langman et al: Journal of the American Medical Association 1999; 282: 1929-1933
Expires December 2002

The study

Double-blinded ?concealed randomised trial ?with intention-to-treat
Setting: acute hospitals around the world

5435 patients (aged 38 to 94; mean 63, 73% female) with osteoarthritis (mainly knee or hip)

Excluded if
  • asymptomatic ulcer diagnosed on endoscopy before randomisation

Control Group: (n = 1564, 1564 analysed): ibuprofen 800 mg three times a day, diclofenac 50 mg three times a day, or nambutone 1500 mg daily
Experimental Group: (n = 3357, 3357 analysed): rofecoxib 12.5 mg, 25 mg or 50 mg daily

91% followed for 4 months - 68% completed the course of medication

The evidence

Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
discontinued medication 4 months 580
(37.1%)		 1034
(30.1%)		 17%
(10% to 23%)		 6.28%
(3.43% to 9.14%)		 16
(11 to 29)
discontinuation due to adverse GI symptoms 4 months 75
(4.80%)		 118
(3.52%)		 27%
(3% to 45%)		 1.28%
(0.05% to 2.51%)		 78
(40 to 1933)
gastroduodenal ulcer on endoscopy 4 months 127
(8.12%)		 64
(1.91%)		 77%
(68% to 83%)		 6.21%
(4.78% to 7.64%)		 16
(13 to 21)
GI perforation, symptomatic gastroduodenal ulcer or upper GI bleeding 4 months 24
(1.53%)		 19
(0.57%)		 63%
(33% to 80%)		 0.97%
(0.31% to 1.63%)		 103
(61 to 324)

Comments

  1. Data pooled from 8 separate double-blind randomised controlled trials (phase 2b/3 studies).
  2. This study was supported by the drug company manufacturing rofecoxib.

Citation

  1. Langman MJ, Jensen DM, Watson DJ, et al: adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. Journal of the American Medical Association 1999; 282: 1929-1933
Contributor: Chris Ball and Musab Hayatli, December 1999
Reviewer:

Clinical Question.
Patient osteoarthritis
Intervention or Exposure rofecoxib
Comparison NSAIDs
Outcome discontinued medication, GI adverse effects