Upper GI bleed: NSAIDs increased the risk, but ibuprofen and diclofenac were the safest.

Clinical bottom line (level 3b)

  1. Patients who took non-aspirin NSAIDs were at increased risk of having a bleeding peptic ulcer in the next 3 months (NNH = 570 at 3 months) .
  2. Ibuprofen and diclofenac were the safest drugs to take.
  3. The risk increased with higher daily doses.
Langman et al: Lancet 1994; 343: 1075-1078
Expires October 2002

The study

Case-control study with objective outcomes, adjusted for confounding factors, not validated in an independent set of patients.

Setting: 5 acute hospitals, UK

3259 patients (aged , 55% male)

Excluded if
  • acute MI, acute rheumatic disease, or active non-bleeding ulcers
  • aged < 60


Cases: 1144 patients (55% male, mean age -): with acute upper GI bleeding due to duodenal or gastric ulcers (confirmed on endoscopy or surgery)
Controls: 2115 patients (56% male, mean age -): hospital or community control matched for age and sex

Factors studied:

previous history of proven peptic ulcer disease, history of dyspepsia, smoking, alcohol intake, age, sex



Factors summarised:

  • non-aspirin NSAID use within the previous 3 months
  • ibuprofen
  • diclofenac
  • naproxen
  • indomethacin
  • piroxicam
  • ketoprofen
  • azapropazone
  • low dose equivalent to ibuprofen < 1200 mg daily, diclofenac < 75 mg daily
  • medium dose
  • high dose equivalent to ibuprofen > 1800 mg daily, diclofenac 150 mg daily


Outcomes studied:
  • bleeding peptic ulcer

 

The evidence

Patient expected event rate for bleeding peptic ulcer: 0.05%
risk factor for
bleeding peptic ulcer 		adjusted OR
(95% CI)		 NNH
(95% CI)
non-aspirin NSAID use 4.5
(3.6 to 5.6) 		570
(440 to 770)
ibuprofen 2.0
(1.4 to 2.8) 		2000
(1100 to 5000)
diclofenac 4.2
(2.6 to 6.8) 		630
(350 to 1300)
naproxen 9.1
(5.5 to 15.1) 		250
(140 to 450)
indomethacin 11.3
(6.3 to 20.3) 		200
(110 to 380)
piroxicam 13.7
(7.1 to 26.3) 		160
(80 to 330)
ketoprofen 23.7
(7.6 to 74.2) 		89
(28 to 300)
azapropazone 31.5
(10.3 to 96.9) 		67
(22 to 220)
low dose 2.5
(1.7 to 3.8) 		1300
(80 to 2900)
medium dose 4.5
(3.3 to 6.0) 		570
(400 to 870)
high dose 8.6
(5.8 to 12.6) 		260
(170 to 420)

Citation

  1. Langman MJ, Weil J, Wainwright P, et al: Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994; 343: 1075-1078
Contributor: Chris Ball and Musab Hayatli, October 1999
Reviewer: Goutham Rao

Clinical Question.
    Patient adult
    Intervention or Exposure NSAID use
    Outcome bleeding peptic ulcer