Table 3.
Adjusted RR of safety outcomes during current exposure compared with past exposure (of same medication class) overall and stratified by exposure characteristics
| Exposure characteristics | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Medication possession ratio | |||||||||
| Safety outcome | Exposure | Overall RR(95% CI)[n] | First Rx RR(95% CI)[n] | Long gap RR(95% CI)[n] | Low RR(95% CI)[n] | Medium RR(95% CI)[n] | High RR(95% CI)[n] | Very high RR(95% CI)[n] | Proportionality of hazard rates in the 3 years following a prescription† |
| Upper GI | Ibuprofen alone | 1.18 (1.13, 1.24) [1 932] | 1.19 (1.05, 1.33)* [293] | 1.15 (1.03, 1.29) [317] | 1.04 (0.91, 1.19) [218] | 0.88 (0.73, 1.05)* [114] | 1.29 (1.08, 1.53) [130] | 1.61 (1.46, 1.78)* [440] | = |
| Paracetamol alone | 1.36 (1.31, 1.41) [3 033] | 1.74 (1.53, 1.99) [235] | 1.30 (1.17, 1.46) [336] | 1.11 (1.04, 1.21) [824] | 1.25 (1.12, 1.38) [399] | 1.49 (1.29, 1.71) [208] | 1.49 (1.34, 1.66) [367] | = | |
| Concomitant ibu + para | 1.70 (1.32, 2.19) [122] | 2.27 (1.09, 4.72) [8] | 1.45 (0.75, 2.81) [10] | 1.02 (0.51, 2.05) [9] | 1.93 (1.04, 3.57) [12] | 1.43 (0.66, 3.13) [7] | 2.10 (1.40, 3.17) [37] | Reference | |
| Myocardial infarction | Ibuprofen alone | 1.09 (1.04, 1.14) [1 688] | 0.94 (0.81, 1.09) [181] | 1.22 (1.09, 1.37) [301] | 1.06 (0.93, 1.21) [237] | 1.04 (0.89, 1.22) [158] | 1.25 (1.07, 1.47) [151] | 1.07 (0.97, 1.19) [368] | = |
| Paracetamol alone | 1.14 (1.10, 1.19) [2 761] | 1.42 (1.22, 1.65) [177] | 0.98 (0.86, 1.11) [254] | 1.11 (1.02, 1.19) [860] | 1.17 (1.05, 1.29) [407] | 1.04 (0.89, 1.23) [157] | 1.17 (1.04, 1.32) [313] | = | |
| Concomitant ibu + para | 1.12 (0.86, 1.46) [88] | 1.31 (0.48, 3.60) [4] | 0.97 (0.42, 2.23) [6] | 1.03 (0.53, 2.01) [10] | 0.80 (0.35, 1.85) [6] | 0.65 (0.24, 1.80) [4] | 1.18 (0.75, 1.87) [28] | Reference | |
| Stroke | Ibuprofen alone | 1.11 (1.06, 1.16) [1 757] | 1.08 (0.94, 1.25) [187] | 0.91 (0.79, 1.04) [214] | 0.99 (0.86, 1.13) [227] | 1.01 (0.87, 1.18) [166] | 1.13 (0.96, 1.33) [148] | 1.23 (1.12, 1.35) [493] | = |
| Paracetamol alone | 1.14 (1.10, 1.18) [4 285] | 1.17 (1.02, 1.35) [214] | 1.14 (1.03, 1.25) [453] | 1.03 (0.97, 1.10) [1248] | 1.17 (1.08, 1.27) [655] | 1.02 (0.89, 1.15) [249] | 1.30 (1.19, 1.41) [600] | = | |
| Concomitant ibu + para | 1.30 (1.01, 1.66) [121] | 1.72 (0.69, 4.25) [5] | 1.32 (0.66, 2.65) [9] | 1.15 (0.62, 2.12) [12] | 1.19 (0.61, 2.31) [10] | 1.03 (0.47, 2.25) [7] | 1.40 (0.94, 2.09) [38] | Reference | |
| Heart failure | Ibuprofen alone | 1.08 (1.03, 1.12) [2 314] | 1.04 (0.91, 1.19) [218] | 1.11 (0.98, 1.25) [286] | 0.89 (0.79, 1.01) [252] | 1.02 (0.89, 1.16) [213] | 1.22 (1.06, 1.40) [212] | 1.31 (1.21, 1.42) [707] | = |
| Paracetamol alone | 1.19 (1.16, 1.23) [5 673] | 1.52 (1.36, 1.69) [355] | 1.23 (1.13, 1.34) [579] | 1.06 (1.00, 1.12) [1 566] | 1.21 (1.12, 1.30) [810] | 1.37 (1.24, 1.52) [398] | 1.38 (1.28, 1.50) [733] | = | |
| Concomitant ibu + para | 1.05 (0.84, 1.32) [1 54] | 0.91 (0.29, 2.88) [3] | 0.97 (0.45, 2.10) [7] | 0.88 (0.47, 1.66) [11] | 1.05 (0.56, 1.98) [11] | 1.12 (0.58, 2.18) [10] | 1.41 (0.98, 2.04) [51] | Reference | |
| Renal failure | Ibuprofen alone | 1.09 (1.00, 1.18) [442] | 1.46 (1.12, 1.89) [59] | 0.88 (0.67, 1.16) [54] | 0.85 (0.64, 1.13) [48] | 0.86 (0.61, 1.21) [34] | 1.10 (0.78, 1.55) [33] | 1.42 (1.19, 1.71) [130] | Ibuprofen alone |
| Paracetamol alone | 1.20 (1.14, 1.27) [1 372] | 1.31 (1.03, 1.68) [66] | 1.21 (1.02, 1.43) [142] | 1.16 (1.04, 1.29) [423] | 1.27 (1.10, 1.47) [217] | 1.44 (1.18, 1.75) [109] | 1.34 (1.15, 1.57) [182] | Paracetamol alone | |
| Concomitant ibu + para | 1.04 (0.67, 1.60) [23] | 2.35 (0.55, 10.10) [2] | 0.53 (0.07, 3.96) [1] | 0.39 (0.05, 2.91) [1] | – | 1.90 (0.56, 6.45) [3] | 1.63 (0.75, 3.54) [10] | Reference | |
| Suicidal behaviour | Ibuprofen alone | 1.40 (1.32, 1.49) [1 072] | 1.13 (0.99, 1.30) [226] | 1.19 (1.03, 1.37) [191] | 1.58 (1.33, 1.88) [135] | 1.14 (0.84, 1.54) [42] | 1.51 (1.10, 2.08) [39] | 1.71 (1.41, 2.06) [111] | = |
| Paracetamol alone | 1.40 (1.29, 1.52) [692] | 1.10 (0.85, 1.41) [64] | 1.23 (0.98, 1.55) [78] | 1.28 (1.08, 1.51) [157] | 1.69 (1.33, 2.14) [74] | 1.83 (1.31, 2.57) [35] | 2.33 (1.84, 2.94) [77] | = | |
| Concomitant ibu + para | 1.50 (0.98, 2.31) [31] | 2.08 (0.88, 4.93) [6] | 1.43 (0.56, 3.63) [5] | 1.42 (0.51, 4.00) [4] | 0.82 (0.11, 6.03) [1] | 2.19 (0.52, 9.18) [2] | 1.36 (0.48, 3.91) [4] | Reference | |
| Overdose | Ibuprofen alone | 1.52 (1.43, 1.62) [1 130] | 1.19 (1.04, 1.37) [219] | 1.28 (1.11, 1.48) [201] | 1.77 (1.50, 2.08) [150] | 1.03 (0.75, 1.41) [39] | 1.62 (1.20, 2.19) [43] | 2.03 (1.71, 2.41) [137] | = |
| Paracetamol alone | 1.42 (1.32, 1.53) [820] | 1.22 (0.96, 1.56) [71] | 1.09 (0.87, 1.37) [79] | 1.27 (1.09, 1.48) [196] | 1.85 (1.52, 2.26) [108] | 1.73 (1.28, 2.34) [44] | 2.12 (1.72, 2.63) [94] | = | |
| Concomitant ibu + para | 1.33 (0.90, 1.96) [37] | 2.00 (0.90, 4.43) [7] | 1.36 (0.58, 3.17) [6] | 1.60 (0.68, 3.77) [6] | 0.58 (0.08, 4.25) [1] | 1.51 (0.36, 6.30) [2] | 1.17 (0.46, 3.02) [5] | Reference | |
| Mortality | Ibuprofen alone | 1.12 (1.10, 1.15) [7 265] | 1.44 (1.35, 1.54)* [948] | 1.00 (0.93, 1.07)* [850] | 0.80 (0.74, 0.86) [681] | 0.87 (0.79, 0.94)* [546] | 1.03 (0.95, 1.13) [535] | 1.31 (1.25, 1.36)* [2325] | = |
| Paracetamol alone | 1.28 (1.26, 1.30) [28 813] | 1.95 (1.87, 2.04) [2176] | 1.18 (1.14, 1.23) [2771] | 0.95 (0.92, 0.97) [6784] | 1.08 (1.05, 1.12) [3821] | 1.27 (1.21, 1.33)* [2012] | 1.63 (1.58, 1.68) [5201] | = | |
| Concomitant ibu + para | 1.50 (1.34, 1.68) [623] | 1.78 (1.23, 2.59) [30] | 1.57 (1.16, 2.12) [47] | 0.93 (0.67, 1.28) [41] | 1.23 (0.89, 1.69) [43] | 0.86 (0.58, 1.30) [2 5] | 1.72 (1.45, 2.04) [226] | Reference | |
*
P value <0.05 comparing the RR during current exposure with ibuprofen only or paracetamol only with the RR during current exposure of similar characteristics to concomitant paracetamol and ibuprofen (i.e. RR in same column).
†
Test for proportionality of RR over time after prescription, from current to past exposure, in an analysis (stratified by exposure characteristics and adjusted for age, gender and calendar year): = indicates that the RR were statistically proportional over time (P value of test for proportionality >0.05) and that the RR did not change despite changes in exposure; if there was a statistical interaction between RR and time, the table lists the subgroup with an increased hazard rate during current exposure. ibu, ibuprofen; para, paracetamol; RR, relative rates; [n], number of cases during current exposure (no prescribing of other NSAIDs or aspirin in the preceding 6 months).