Table 4.
Major bleeding risk among patients using apixaban, dabigatran or rivaroxaban with the concomitant use of drugs with pharmacodynamics interaction
| Concurrent use of * | Apixaban | Dabigatran | Rivaroxaban | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cases (n = 53), n (%) | Controls (n = 279), n (%) | Crude OR (95% CI) | Adjusted OR* (95% CI) | Cases (n = 79), n (%) | Controls (n = 366), n (%) | Crude OR (95% CI) | Adjusted OR* (95% CI) | Cases (n = 261), n (%) | Controls (n = 849), n (%) | Crude OR (95% CI) | Adjusted OR** (95% CI) | |
| Interacting drugs | 14 (26.4) | 34 (12.2) | 2.59 (1.27–5.25) | 3.32 (1.43–7.71) | 18 (22.8) | 47 (12.8) | 2.00 (1.09–3.68) | 3.00 (1.48–6.1) | 53 (20.3) | 121 (14.3) | 1.53 (1.07–2.19) | 1.39 (0.93–2.06) |
| SSRIs | 6 (11.3) | 13 (4.7) | 2.22 (0.60–8.21) | 2.78 (0.78–9.91) | 10 (12.7) | 20 (5.5) | 2.51 (1.12–5.59) | 2.70 (1.09–6.70) | 25 (9.6) | 62 (7.3) | 1.35 (0.83–2.19) | 1.23 (0.73–2.07) |
| Antiplatelet dugs | 6 (11.3) | 19 (6.8) | 2.30 (0.60–8.86) | 2.07 (0.66–6.49) | 9 (11.4) | 24 (6.6) | 1.83 (0.82–4.11) | 2.81 (1.05–7.51) | 26 (10.0) | 47 (5.5) | 1.89 (1.14–3.12) | 1.69 (0.97–2.94) |
| ASA | <5 | 12 (4.3) | *, ** | *** | 5 (6.3) | 17 (4.6) | 1.44 (0.51–4.02) | 1.90 (0.58–6.25) | 18 (6.9) | 33 (3.9) | 1.86 (1.03–3.37) | 1.71 (0.89–3.29) |
| CLOP | <5 | 6 (2.2) | *** | *** | <5 | 6 (1.6) | 1.63 (0.32–8.24) | 3.05 (0.44–21.34) | 6 (2.3) | 11 (1.3) | 1.86 (0.68–5.09) | 1.66 (0.56–4.89) |
| ASA+ CLOP | 0 | <5 | *** | *** | <5 | <5 | *** | *** | <5 | <5 | *** | *** |
| NSAIDs | <5 | <5 | *** | *** | <5 | <5 | *** | *** | <5 | 10 (1.2) | *** | *** |
All the concurrent used drugs with direct oral anticoagulants were compared with direct oral anticoagulant use without these drugs.
Adjusted for age, gender, body mass index, smoking, history of major bleeding, history of stroke or transient ischaemic attack before the bleeding event, diabetes, hypertension, myocardial infarction, congestive heart failure, chronic renal disease, hepatic impairment, peripheral vascular disease, chronic pulmonary disease, peptic ulcer disease, cancer, comedications before the index date medications (β‐adrenergic receptor blockers, angiotensin‐converting‐enzyme inhibitors, non‐P‐gp inhibitor statins, proton pump inhibitors, and cytochrome P450 enzyme inducers). For analysing the association of potentially pharmacokinetic interacting drugs we also adjusted for potentially pharmacodynamic interacting drugs and vice versa. ASA: acetylsalicylic acid; CI: confidence interval; CLOP: clopidogrel; NSAIDs, nonsteroidal anti‐inflammatory drug; OR: odds ratio; SSRIs, selective serotonin reuptake inhibitors.
Suppressed due to <5 patients (Clinical Practice Research Datalink policy).