Table A5.
Association between use of concomitant drugs in current users of DOACs and risk of major bleeding (Sensitivity 60days)
| Concurrent use of* | Cases (n = 393), n (%) | Controls (n = 1494), n (%) | Crude OR (95% CI) | Adjusted OR** (95% CI) |
|---|---|---|---|---|
| Drugs with PK interaction, n (%) | 224 (57.0) | 936 (62.7) | 0.80 (0.635–1.00) | 0.94 (0.64–1.39) |
| Amiodarone | 10 (2.5) | 51 (3.4) | 0.74 (0.38–1.48) | 0.71 (0.34–1.48) |
| Simvastatin | 95 (24.2) | 467 (31.3) | 0.71 (0.55–0.92) | 0.84 (0.58–1.20) |
| Atorvastatin | 76 (19.3) | 294 (19.7) | 1.00 (0.75–1.33) | 1.18 (0.82–1.70) |
| Verapamil | 5 (1.3) | 18 (1.2) | 1.11 (0.41–3.04) | 1.94 (0.64–5.83) |
| Digoxin | 65 (16.5) | 228 (15.3) | 1.09 (0.80–1.48) | 1.06 (0.76–1.48) |
| Diltiazem | 11 (2.8) | 82 (5.5) | 0.49 (0.26–0.94) | 0.37 (0.18–0.74) |
| Drugs with PD interaction, n (%) | 123 (31.3) | 278 (18.6) | 2.02 (1.56–2.61) | 2.10 (1.58–2.78) |
| SSRIs | 53 (13.5) | 113 (7.6) | 1.94 (1.35–2.79) | 1.91 (1.29–2.83) |
| Antiplatelet drugs | 70 (17.8) | 146 (9.8) | 1.97 (1.45–2.69) | 2.00 (1.36–2.95) |
| ASA only | 46 (11.7) | 103 (6.9) | 1.82 (1.25–2.64) | 1.88 (1.25–2.84) |
| CLOP only | 14 (3.6) | 33 (2.2) | 1.74 (0.92–3.30) | 1.59 (0.78–3.21) |
| > 1 drug | 9 (2.3) | 7 (0.5) | 5.26 (1.95–14.15) | 6.19 (2.12–18.03) |
| NSAIDs | 9 (2.3) | 29 (1.9) | 1.16 (0.54–2.48) | 1.16 (0.51–2.64) |
ASA, acetylsalicylic acid; CLOP, clopidogrel. PK, P‐gP inhibitors or CYP3A4 inhibitors; PD, pharmacodynamic.
All the concurrent used drugs with DOACs were compared to use DOACs but without use these drugs.
Adjusted for smoking, alcohol abuse, 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‐PgP inhibitor statins, proton pump inhibitors, and cytochrome P450 enzyme inducers). For evaluating the association between pharmacodynamic interacting drugs and the major bleeding, co‐medications with potential pharmacokinetic interactions were adjusted for. For evaluating the association between the combination use of pharmacokinetic interactions and DOAC and the major bleeding, drugs with potential pharmacodynamic interactions were adjusted for.
Suppressed due to <5 patients CPRD policy).