Table 4

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

Intervention†Adverse eventsRR (95% CI)Category of evidence
*RR, relative risk between treatment group and control group; RR = 1, no different from the control population; RR>1, more risky than the control population; RR<1, less risky than the control population. Pooled RR was estimated for more than one study; †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.
ParacetamolGI discomfort0.80 (0.27 to 2.37)RCTs
GI perforation/bleed3.60 (2.60 to 5.10)Case-control study
GI bleeding1.2 (0.8 to 1.7)Case-control studies
Renal failure0.83 (0.50 to 1.39)Cohort study
Renal failure2.5 (1.7 to 3.6)Case-control study
NSAIDsGI perforation/ulcer/bleed5.36 (1.79 to 16.10)RCTs
GI perforation/ulcer/bleed2.70 (2.10 to 3.50)Cohort studies
GI perforation/ulcer/bleed3.00 (2.70 to 3.70)Case-control studies
Coxibs v NSAIDsEndoscopic GI ulcer0.18 (0.14 to 0.23)RCTs
CV events0.79 (0.40 to 1.55)RCTs
Coxibs v naproxenCV events1.69 (1.07 to 2.69)RCTs
MisoprostolEndoscopic GI ulcer0.26 (0.17 to 0.39)RCTs
Diarrhoea1.81 (1.52 to 2.16)RCTs
H2 Blockers (double doses)Endoscopic GI ulcer0.44 (0.03 to 0.74)RCTs
PPIsEndoscopic GI ulcer0.40 (0.32 to 0.51)RCTs
Opioids+paracetamol v paracetamolGI upset/constipation14.00 (1.86 to 105.16)RCT
DiacerheinDiarrhoea3.73 (2.61 to 5.32)RCT
Skin rash/pruritus2.40 (1.01 to 5.69)RCT