The ability of Misoprostol to seduce serious gastrointestinal complications due to chronic NSAID use.

Christopher H.Chay, MD.
July 25, 1997

Clinical scenario:

1. Serious gastrointestinal complications as defined by strict criteria showed a relative risk reduction of 40% with an absolute risk reduction of 0.38% (41 of 4439 patients on placebo and 25 or 4404 on misoprostol.)

2. The dropout rate was large with 42% of the misoprostol treatment group and 36% of the placebo group with 19% of the dropout group having a history of peptic ulcer disease compared to 13% of those who completed the study.

3. Age => 75 (Odds Ratio: 2.48), history of peptic ulcer disease (OR:2.29), history of gastrointestinal bleeding (OR: 2.56), and history of cardiac disease (OR: 1.84) were found to be risk factors for serious upper gastrointestinal complications.

4. Despite the primarily clinical basis of this study, the relative risk reduction of adding misoprostol to NS AID use correlates with prior endoscopic based studies. This study adds generalizability with multiple NS AIDs as well as multiple clinical endpoints.

The Evidence:

Large, Randomized, Double Blind, Placebo-Controlled Trial comparing 8843 men and women on NSAIDs with misoprostol versus placebo use.

Variable All Patients Patients with Events 1 to 8 Odds Ratio (95% CI)

n (%)
Risk factor
Age=>75 years 1419 (16.0) 23 (34.3) 2.48 (1.48 to 4.14)
History of peptic ulcer 1281 (14.5) 24 (35.8) 2.29 (1.28 to 4.12)
History of gastrointestinal bleeding 573 (6.5) 15 (22.4) 2.56 (1.30 to 5.03)
History of heart disease 4831 (54.6) 48 (71.6) 1.84 (1.07 to 3.15)
Treatment Factor
Misoprostol treatment 4404 (49.8) 25 (37.3) 0.60 (0.36 to 0.98)

Comments:

1. The large nature of this study leads itself to generizability but compromises the absolute risk reduction 0.38% despite a relative risk reduction of 40%. Because of this the number of patients needed to treat (NNT)= 264 to prevent one serious gastrointestinal complication.

2. Four risk factors were identified, the number of patients with a history of cardiac disease was not reported and of those patients with age => 75 a significant number more were found in the placebo group (n=724) than the misoprostol group (n=695).

3. With 0/4 risk: factors the NNT= 625, with 4/4 risk factors the NNT= 28, and with the three major criteria of age=>75, history of peptic ulcer disease, and history of gastrointestinal bleeding the NNT= 47.

4. The large dropout rate was greater in the misoprostol treat group 42% as compared with the placebo group 36%. In addition 19% of those who withdrew had a history of peptic ulcer disease, a major risk favor, compared to 13% of those who completed the study. In addition the endpoints of those who withdrew went unreported.

Reference:
Silverstein F.et al. Misoprostol Reduces Serious Gastrointestinal Complications in Patients with Rheumatoid Arthritis Receiving Nonsteroidal Anti-Inflammatory Drugs. Annals of Internal Medicine. 1995; 123: 241-249.