Table 3.
Subgroup analyses of risk of intracranial haemorrhage with combined use of antidepressants and non-steroidal anti-inflammatory drugs (NSAIDs), compared with antidepressants use without NSAIDs, in propensity based matched cohort
| Subgroup | Hazard ratio (95% CI)* | P value for interaction |
|---|---|---|
| Age | ||
| <45 years (n=1 285 011) | 2.2 (1.24 to 3.80) | 0.234 |
| ≥45 years (n=2 860 215) | 1.5 (0.87 to 2.67) | |
| Sex | ||
| Male (n=1 600 710) | 2.6 (1.93 to 3.42) | <0.001 |
| Female (n=2 544 516) | 1.2 (0.89 to 1.57) | |
| Subtype of intracranial haemorrhage (n=4 145 226) | ||
| Subarachnoid haemorrhage (I60) (n=262) | 1.3 (1.05 to 1.52) | † |
| Intracerebral haemorrhage (I61) (n=313) | 1.3 (1.08 to 1.55) | |
| Other non-traumatic intracranial haemorrhage (I62) (n=167) | 1.3 (1.08 to 1.57) | |
| History of comorbidities in previous year | ||
| Diabetes: | 0.002 | |
| Yes (n=521 696) | 1.1 (0.86 to 1.30) | |
| No (n=3 623 530) | 1.9 (1.53 to 2.29) | |
| Chronic obstructive pulmonary disease: | 0.003 | |
| Yes (n=620 779) | 3.7 (3.13 to 4.46) | |
| No (n=3 524 447) | 1.4 (1.21 to 1.72) | |
| Hypertension: | <0.001 | |
| Yes (n=1 107 587) | 1.0 (0.80 to 1.30) | |
| No (n=3 037 639) | 2.4 (1.87 to3.03) | |
| Dyslipidaemia: | 0.455 | |
| Yes (n=154 933) | 2.1 (1.75 to 2.46) | |
| No (n=3 990 293) | 1.5 (1.30-1.84) | |
| Osteoarthritis: | 0.052 | |
| Yes (n=849 327) | 1.2 (0.98 to 1.44) | |
| No (n=3 295 899) | 1.7 (1.42 to 2.10) | |
| Rheumatoid arthritis: | 0.010 | |
| Yes (n=81 271) | 0.2 (0.18 to 0.25) | |
| No (n=4 063 955) | 1.6 (1.38 to 1.94) | |
| Osteoporosis: | 0.009 | |
| Yes (n=321 711) | 0.8 (0.69 to 0.98) | |
| No (n=3 823 515) | 1.7 (1.42 to 2.04) | |
| Alcohol related disorder: | 0.868 | |
| Yes (n=75 057) | 1.7 (1.40 to 1.98) | |
| No (n=4 070 169) | 1.6 (1.31 to 1.86) | |
| Ischaemic heart disease: | <0.001 | |
| Yes (n=223 039) | 0.8 (0.69 to 0.99) | |
| No (n=3 922 187) | 1.8 (1.48 to 2.13) | |
| Chronic kidney disease: | 0.026 | |
| Yes (n=56 031) | 0.5 (0.43 to 0.60) | |
| No (n=4 089 195) | 1.6 (1.38 to 1.94) | |
| Peptic ulcer: | 0.023 | |
| Yes (n=772 740) | 1.1 (0.90 to 1.32) | |
| No (n=3 372 486) | 1.7 (1.43 to 2.08) | |
| Non-alcoholic liver disease: | 0.823 | |
| Yes (n=364 689) | 1.6 (1.38 to 1.97) | |
| No (n=3 780 537) | 1.6 (1.30 to 1.86) | |
| Neoplasm: | 0.692 | |
| Yes (n=611 623) | 1.5 (1.22 to 1.78) | |
| No (n=3 533 603) | 1.6 (1.32 to 1.93) | |
| Heart failure: | 0.071 | |
| Yes (n=44 616) | 9.9 (8.30 to 11.68) | |
| No (n=4 100 610) | 1.5 (1.28 to 1.80) | |
| Disease of arteries: | 0.021 | |
| Yes (n=262 085) | 0.6 (0.47 to 0.66) | |
| No (n=3 883 141) | 1.6 (1.38 to 1.95) | |
| Disease of veins: | 0.149 | |
| Yes (n=210 315) | 1.0 (0.84 to 1.18) | |
| No (n=3 934 911) | 1.6 (1.36 to 1.93) | |
| Drug use in previous year | ||
| Low dose aspirin: | 0.317 | |
| Yes (n=521 621) | 1.3 (1.10 to 1.59) | |
| No (n=3 623 605) | 1.6 (1.35 to 1.96) | |
| Platelet aggregation inhibitors: | 0.0026 | |
| Yes (n=253 222) | 0.7 (0.59 to 0.84) | |
| No (n=3 892 004) | 1.7 (1.44 to 2.05) | |
*Adjusted for dementia, warfarin, heparin group, and steroids as time varying covariates, using matched Cox regression models.
†P value for interaction not calculated, because subtype of intracranial haemorrhage was an outcome variable.