Table 4 Evidence of safety—pooled relative risk (RR) or odds ratio (OR)* and 95% confidence interval (CI).
| Intervention† | Adverse events | RR/OR (95% CI) | Evidence | References | |
|---|---|---|---|---|---|
| Paracetamol | GI discomfort | 0.80 (0.27 to 2.37) | RCTs | 48 | |
| GI perforation/bleed | 3.60 (2.60 to 5.10) | Case‐control study | 49 | ||
| GI bleeding | 1.2 (0.8 to 1.7) | Case‐control studies | 50 | ||
| Renal failure | 2.5 (1.7 to 3.6) | Case‐control study | 51 | ||
| Renal failure | 0.83 (0.50 to 1.39) | Cohort study | 52 | ||
| Topical NSAIDs | GI events | 0.81 (0.43 to 1.56) | RCTs | 25 | |
| GI bleed/perforation | 1.45 (0.84 to 2.50) | Case‐control | 42 | ||
| Glucosamine sulphate preparations | Any | 0.97 (0.88 to 1.08) | RCTs | 53 | |
| Diacerhein | Diarrhoea | 3.98 (2.90 to 5.47) | RCTs | 54, 55 | |
| NSAIDs | GI perforation/ulcer/bleed | 5.36 (1.79 to 16.10) | RCTs | 56 | |
| GI perforation/ulcer/bleed | 2.70 (2.10 to 3.50) | Cohort studies | 56 | ||
| GI perforation/ulcer/bleed | 3.00 (2.70 to 3.70) | Case‐control studies | 56 | ||
| GI protective strategies versus NSAID alone | |||||
| H2 blocker+NSAID | Serious GI complications | 0.33 (0.01 to 8.14) | RCTs | 57 | |
| Symptomatic ulcers | 1.46 (0.06 to 35.53) | RCTs | 57 | ||
| Serious CV or renal events | 0.53 (0.08 to 3.46) | RCTs | 57 | ||
| PPI+NSAID | Serious GI complications | 0.46 (0.07 to 2.92) | RCTs | 57 | |
| Symptomatic ulcers | 0.09 (0.02 to 0.47) | RCTs | 57 | ||
| Serious CV or renal events | 0.78 (0.10 to 6.26) | RCTs | 57 | ||
| Misoprostol+NSAID | Serious GI complications | 0.57 (0.36 to 0.91) | RCTs | 57 | |
| Symptomatic ulcers | 0.36 (0.20 to 0.67) | RCTs | 57 | ||
| Serious CV or renal events | 1.78 (0.26 to 12.07) | RCTs | 57 | ||
| Diarrhoea | 1.81 (1.52 to 2.61) | RCTs | 58 | ||
| COX‐2 selective | Serious GI complications | 0.61 (0.34 to 1.10) | RCTs | 57 | |
| Symptomatic ulcers | 0.41 (0.26 to 0.65) | RCTs | 57 | ||
| Serious CV or renal events | 0.95 (0.55 to 1.66) | RCTs | 57 | ||
| COX‐2 specific (coxibs) | Serious GI complications | 0.55 (0.38 to 0.80 | RCTs | 57 | |
| Symptomatic ulcers | 0.49 (0.38 to 0.62) | RCTs | 57 | ||
| Serious CV or renal events | 1.19 (0.80 to 1.75) | RCTs | 57 | ||
| Surgery | |||||
| T+LRTI/IA v T | Any | 2.12 (1.24 to 3.60) | RCTs | 29 | |
| TJR v T+IA | Any | 5.00 (0.26 to 95.02) | RCTs | 29 |
*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.