Table 4

 Evidence of safety—pooled relative risk (RR) or odds ratio (OR)* and 95% confidence interval (CI)

Intervention†Adverse eventsRR/OR (95% CI)EvidenceReferences
*RR was calculated for an RCT or cohort study and OR was for a case-control study. RR (or OR)  = 1: no difference between treatment and control; RR (or OR)>1: more risky with treatment; RR <1: less risky with treatment. The results were pooled if more than one study was involved; †compared with placebo/non-exposure unless otherwise stated.
H2-blockers, histamine type 2 receptor antagonists; PPIs, proton pump inhibitors; GI, gastrointestinal; CV, cardiovascular; CNS, central nervous system; T, trapeziectomy; LRTI, ligament reconstruction and tendon interposition; IA, interposition arthroplasty; TJR, total joint replacement.
ParacetamolGI discomfort0.80 (0.27 to 2.37)RCTs48
GI perforation/bleed3.60 (2.60 to 5.10)Case-control study49
GI bleeding1.2 (0.8 to 1.7)Case-control studies50
Renal failure2.5 (1.7 to 3.6)Case-control study51
Renal failure0.83 (0.50 to 1.39)Cohort study52
Topical NSAIDsGI events0.81 (0.43 to 1.56)RCTs25
GI bleed/perforation1.45 (0.84 to 2.50)Case-control42
Glucosamine sulphate preparationsAny0.97 (0.88 to 1.08)RCTs53
DiacerheinDiarrhoea3.98 (2.90 to 5.47)RCTs54, 55
NSAIDsGI perforation/ulcer/bleed5.36 (1.79 to 16.10)RCTs56
GI perforation/ulcer/bleed2.70 (2.10 to 3.50)Cohort studies56
GI perforation/ulcer/bleed3.00 (2.70 to 3.70)Case-control studies56
GI protective strategies versus NSAID alone
H2 blocker+NSAIDSerious GI complications0.33 (0.01 to 8.14)RCTs57
Symptomatic ulcers1.46 (0.06 to 35.53)RCTs57
Serious CV or renal events0.53 (0.08 to 3.46)RCTs57
PPI+NSAIDSerious GI complications0.46 (0.07 to 2.92)RCTs57
Symptomatic ulcers0.09 (0.02 to 0.47)RCTs57
Serious CV or renal events0.78 (0.10 to 6.26)RCTs57
Misoprostol+NSAIDSerious GI complications0.57 (0.36 to 0.91)RCTs57
Symptomatic ulcers0.36 (0.20 to 0.67)RCTs57
Serious CV or renal events1.78 (0.26 to 12.07)RCTs57
Diarrhoea1.81 (1.52 to 2.61)RCTs58
COX-2 selectiveSerious GI complications0.61 (0.34 to 1.10)RCTs57
Symptomatic ulcers0.41 (0.26 to 0.65)RCTs57
Serious CV or renal events0.95 (0.55 to 1.66)RCTs57
COX-2 specific (coxibs)Serious GI complications0.55 (0.38 to 0.80RCTs57
Symptomatic ulcers0.49 (0.38 to 0.62)RCTs57
Serious CV or renal events1.19 (0.80 to 1.75)RCTs57
    T+LRTI/IA v TAny2.12 (1.24 to 3.60)RCTs29
    TJR v T+IAAny5.00 (0.26 to 95.02)RCTs29