Table 3.
Major bleeding risk among patients taking direct oral anticoagulants (DOACs) with the concomitant use of potentially interacting drugs
| Concurrent use of* | Cases (n = 393), n (%) | Controls (n = 1494), n (%) | Crude OR (95% CI) | Adjusted OR ** (95% CI) |
|---|---|---|---|---|
| Drugs with PK interaction, n (%) | 177 (45.0) | 765 (51.2) | 0.69 (0.62–0.98) | 0.69 (0.53–0.90) |
| Amiodarone | 7 (1.8) | 40 (2.7) | 0.66 (0.29–1.48) | 0.67 (0.28–1.59) |
| Simvastatin | 76 (19.3) | 374 (25.0) | 0.72 (0.54–0.95) | 0.69 (0.42–1.13) |
| Atorvastatin | 59 (15.0) | 232 (15.5) | 0.96 (0.71–1.31) | 1.25 (0.83–1.88) |
| Verapamil | 5 (1.3) | 12 (0.8) | 1.67 (0.59–4.73) | 1.76 (0.58–5.35) |
| Digoxin | 54 (13.7) | 192 (12.9) | 1.08 (0.78–1.50) | 1.08 (0.75–1.55) |
| Diltiazem | 7 (1.8) | 69 (4.6) | 0.37 (0.17–0.81) | 0.26 (0.11–0.61) |
|
Drugs with PD Interaction, n (%) |
85 (21.6) | 202 (13.5) | 1.79 (1.34–2.40) | 1.88 (1.36–2.61) |
| SSRIs | 41 (10.4) | 95 (6.4) | 1.71 (1.14–2.54) | 1.68 (1.10–2.59) |
| Antiplatelet drugs | 41 (10.4) | 90 (6.0) | 1.79 (1.21–2.64) | 2.01 (1.29–3.11) |
| ASA | 28 (7.1) | 62 (4.1) | 1.76 (1.10–2.82) | 1.94 (1.16–3.26) |
| CLOP | 9 (2.3) | 23 (1.5) | 1.54 (0.70–3.41) | 1.68 (0.71–3.97) |
| ASA + CLOP | <5 | <5 | *, ** | *** |
| NSAIDs | 7 (1.8) | 19 (1.3) | 1.45 (0.60–3.54) | 1.30 (0.50–3.41) |
All the concurrent used drugs with DOACs were compared to use DOACs but without use these drugs.
Adjusted for 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, co‐medications 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).