TABLE 5.
Risk of gastrointestinal hemorrhage among AF patients taking non-vitamin-K antagonist oral anticoagulants with or without concurrent antipsychotics.
| Concurrent medication | Person- quarters with NOAC use | No. of bleeding events | Crude major bleeding incidence rate (95% CI) per 1,000 person-years | Adjusted incidence rate (95% CI) per 1,000 person-years a | Adjusted rate ratio (95% CI) a | Adjusted incidence rate difference (95% CI) per 1,000 person-years | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Typical | ||||||||||
| with | 29,858 | 730 | 96.22 | (89.14 to 103.87) | 98.49 | (91.38 to 106.15) | 2.31 b | (2.13 to 2.50) | 55.77 b | (48.31 to 63.22) |
| without c | 675,663 | 5,760 | 34.46 | (33.49 to 35.46) | 42.72 | (41.34 to 44.15) | 1 | (1.00 to 1.00) | — | — |
| Chlorpromazine | ||||||||||
| with | 963 | 23 | 91.94 | (60.32 to 140.13) | 96.05 | (64.19 to 143.71) | 2.17 b | (1.44 to 3.25) | 51.71 b | (12.94 to 90.49) |
| without c | 704,558 | 6,467 | 37.06 | (36.06 to 38.08) | 44.34 | (42.08 to 46.71) | 1 | (1.00 to 1.00) | — | — |
| Droperidol | ||||||||||
| with | 192 | 7 | 143.31 | (67.87 to 302.64) | 146.11 | (70.52 to 302.71) | 3.28 b | (1.58 to 6.81) | 101.59 | (−4.87 to 208.05) |
| without c | 705,329 | 6,483 | 37.1 | (36.11 to 38.12) | 44.52 | (42.63 to 46.49) | 1 | (1.00 to 1.00) | — | — |
| Flupentixol | ||||||||||
| with | 8,034 | 84 | 41.86 | (33.13 to 52.90) | 42.23 | (33.46 to 53.30) | 1.05 | (0.83 to 1.33) | 2.07 | (−7.83 to 11.98) |
| without c | 697,487 | 6,406 | 37.08 | (36.08 to 38.10) | 40.16 | (38.73 to 41.64) | 1 | (1.00 to 1.00) | — | — |
| Flupentixol/Melitracen | ||||||||||
| with | 7,804 | 79 | 40.46 | (31.73 to 51.60) | 40.88 | (32.11 to 52.05) | 1.02 | (0.80 to 1.30) | 0.69 | (−9.26 to 10.64) |
| without c | 697,717 | 6,411 | 37.1 | (36.10 to 38.12) | 40.19 | (38.75 to 41.67) | 1 | (1.00 to 1.00) | — | — |
| Haloperidol | ||||||||||
| with | 5,613 | 219 | 151.31 | (131.70 to 173.84) | 157.08 | (137.43 to 179.54) | 2.88 b | (2.51 to 3.31) | 102.63 b | (81.57 to 123.69) |
| without c | 699,908 | 6,271 | 36.18 | (35.20 to 37.19) | 54.45 | (52.40 to 56.58) | 1 | (1.00 to 1.00) | — | — |
| Prochlorperazine | ||||||||||
| with | 15,968 | 433 | 105.53 | (95.69 to 116.37) | 108.41 | (98.53 to 119.28) | 2.48 b | (2.25 to 2.74) | 64.73 b | (54.34 to 75.13) |
| without c | 689,553 | 6,057 | 35.5 | (34.52 to 36.51) | 43.68 | (42.30 to 45.09) | 1 | (1.00 to 1.00) | — | — |
| Atypical | ||||||||||
| with | 41,497 | 784 | 75.34 | (69.87 to 81.23) | 76.53 | (71.05 to 82.43) | 1.59 b | (1.46 to 1.73) | 28.3 b | (22.28 to 34.32) |
| without c | 664,024 | 5,706 | 34.71 | (33.73 to 35.73) | 48.22 | (46.13 to 50.41) | 1 | (1.00 to 1.00) | — | — |
| Aripiprazole | ||||||||||
| with | 874 | 15 | 67.01 | (38.83 to 115.64) | 68.85 | (40.56 to 116.88) | 1.5 | (0.88 to 2.56) | 23.04 | (−13.47 to 59.54) |
| without c | 704,647 | 6,475 | 37.1 | (36.10 to 38.12) | 45.81 | (43.43 to 48.34) | 1 | (1.00 to 1.00) | — | — |
| Olanzapine | ||||||||||
| with | 1,662 | 16 | 37.67 | (22.80 to 62.22) | 38.61 | (23.74 to 62.80) | 0.85 | (0.52 to 1.39) | −6.72 | (−25.59 to 12.14) |
| without c | 703,859 | 6,474 | 37.13 | (36.14 to 38.15) | 45.34 | (43.55 to 47.20) | 1 | (1.00 to 1.00) | — | — |
| Quetiapine | ||||||||||
| with | 35,483 | 695 | 78.03 | (72.06 to 84.50) | 79.41 | (73.42 to 85.89) | 1.61 b | (1.48 to 1.76) | 30.15 b | (23.62 to 36.69) |
| without c | 670,038 | 5,795 | 34.94 | (33.95 to 35.95) | 49.26 | (47.15 to 51.47) | 1 | (1.00 to 1.00) | — | — |
| Risperidone | ||||||||||
| with | 5,404 | 109 | 79.72 | (64.68 to 98.25) | 81.51 | (66.40 to 100.07) | 1.67 b | (1.36 to 2.06) | 32.82 b | (16.02 to 49.62) |
| without c | 700,117 | 6,381 | 36.8 | (35.81 to 37.82) | 48.69 | (46.87 to 50.59) | 1 | (1.00 to 1.00) | — | — |
Adjusted by the inverse probability of treatment weighting using the propensity score (gender, age, medical utilization, hypertension, myocardial infarction, congestive heart failure, percutaneous coronary intervention, coronary bypass surgery, peripheral vascular disease, cerebrovascular disease, ischemic stroke, transient ischemic attack, hemiplegia or paraplegia, dementia, epilepsy, diabetes mellitus, chronic kidney disease, chronic pulmonary disease, peptic ulcer disease, liver disease, malignancy, anemia, rheumatic disease, human immunodeficiency virus infection, antibiotics and anti-fungal drugs, anti-epileptics, anti-hypertensives, anti-platelets, bisphosphate, cardiovascular drugs, cyclosporine, glucocorticoid, insulin, lipid-lowering drugs, nonsteroid anti-inflammatory drugs, proton pump inhibitors, residence, income level, and occupation, see Tables 1, 2 and Supplementary Table S3).
p < 0.05, compared with NOAC alone.
Without indicates NOAC alone.