Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis

N Engl J Med. 2002 Dec 26;347(26):2104-10. doi: 10.1056/NEJMoa021907.

Abstract

Background: Current guidelines recommend that patients at risk for ulcer disease who require treatment for arthritis receive nonsteroidal antiinflammatory drugs (NSAIDs) that are selective for cyclooxygenase-2 or the combination of a nonselective NSAID with a proton-pump inhibitor. We assessed whether celecoxib would be similar to diclofenac plus omeprazole in reducing the risk of recurrent ulcer bleeding in patients at high risk for bleeding.

Methods: We studied patients who used NSAIDs for arthritis and who presented with ulcer bleeding. After their ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 200 mg of celecoxib twice daily plus daily placebo or 75 mg of diclofenac twice daily plus 20 mg of omeprazole daily for six months. The end point was recurrent ulcer bleeding.

Results: In the intention-to-treat analysis, which included 287 patients (144 receiving celecoxib and 143 receiving diclofenac plus omeprazole), recurrent ulcer bleeding occurred in 7 patients receiving celecoxib and 9 receiving diclofenac plus omeprazole. The probability of recurrent bleeding during the six-month period was 4.9 percent (95 percent confidence interval, 3.1 to 6.7) for patients who received celecoxib and 6.4 percent (95 percent confidence interval, 4.3 to 8.4) for patients who received diclofenac plus omeprazole (difference, -1.5 percentage points; 95 percent confidence interval for the difference, -6.8 to 3.8). Renal adverse events, including hypertension, peripheral edema, and renal failure, occurred in 24.3 percent of the patients receiving celecoxib and 30.8 percent of those receiving diclofenac plus omeprazole.

Conclusions: Among patients with a recent history of ulcer bleeding, treatment with celecoxib was as effective as treatment with diclofenac plus omeprazole, with respect to the prevention of recurrent bleeding. Renal toxic effects are common in high-risk patients receiving celecoxib or diclofenac plus omeprazole.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Anti-Ulcer Agents / therapeutic use
  • Arthritis / drug therapy*
  • Celecoxib
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / adverse effects
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Diclofenac / adverse effects
  • Diclofenac / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Duodenal Ulcer / chemically induced
  • Duodenal Ulcer / prevention & control
  • Helicobacter pylori / isolation & purification
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Membrane Proteins
  • Omeprazole / therapeutic use
  • Peptic Ulcer Hemorrhage / chemically induced
  • Peptic Ulcer Hemorrhage / prevention & control*
  • Probability
  • Prospective Studies
  • Prostaglandin-Endoperoxide Synthases
  • Pyrazoles
  • Risk Factors
  • Secondary Prevention
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / prevention & control
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anti-Ulcer Agents
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Pyrazoles
  • Sulfonamides
  • Diclofenac
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Celecoxib
  • Omeprazole