Table 4.
Factors associated with early bleeding among warfarin initiators (n=101,588)
| Factors | Age-adjusted HR (95% CI) | Multivariable-adjusted HR (95% CI)a | Multivariable-adjusted HR (95% CI)b |
|---|---|---|---|
| Sex | |||
| Men | 1.30 (1.09–1.55) | 1.32 (1.10–1.57) | 1.34 (1.11–1.60) |
| Age | |||
| Per 10 years | NA | 1.13 (1.04–1.22) | 1.12 (1.04–1.21) |
| Indications | |||
| Atrial fibrillation | 0.87 (0.73–1.03) | 1.00 (0.83–1.21) | 0.98 (0.81–1.19) |
| Venous thrombosis | 1.94 (1.54–2.44) | 1.83 (1.44–2.34) | 1.80 (1.41–2.92) |
| Mechanical heart valve | 1.04 (0.80–1.34) | 0.99 (0.76–1.30) | 0.95 (0.73–1.24) |
| Pulmonary embolism | 1.85 (1.43–2.40) | 1.46 (1.11–1.91) | 1.42 (1.09–1.87) |
| Ischemic stroke or transient ischemic attack | 1.31 (1.01–1.71) | 1.22 (0.93–1.61) | 1.04 (0.77–1.39) |
| History of bleeding | |||
| During 1 day–<180 days before warfarin initiation | 17.7 (14.3–21.9) | NA | NA |
| During 180 days–7 years before warfarin initiation | 2.35 (1.84–2.99) | 1.48 (1.15–1.90) | 1.46 (1.14–1.88) |
| Comorbidities | |||
| Coronary artery disease | 1.04 (0.87–1.24) | 1.00 (0.82–1.21) | 0.95 (0.78–1.15) |
| Heart failure | 1.10 (0.88–1.37) | 1.04 (0.83–1.31) | 0.93 (0.73–1.18) |
| Hypertension | 1.17 (0.98–1.39) | 1.13 (0.94–1.35) | 1.07 (0.89–1.29) |
| Peripheral arterial disease | 1.34 (0.94–1.90) | 1.11 (0.78–1.59) | 1.04 (0.73–1.49) |
| Thrombosis in cerebral arteries or in intracranial veins | 0.97 (0.43–2.16) | 0.75 (0.33–1.68) | 0.72 (0.32–1.62) |
| Diabetes | 0.99 (0.80–1.24) | 0.88 (0.70–1.10) | 0.79 (0.63–1.01) |
| Renal impairment | 1.87 (1.25–2.79) | 1.22 (0.81–1.85) | 1.09 (0.71–1.67) |
| Liver disease | 2.27 (1.28–4.02) | 1.40 (0.77–2.56) | 1.29 (0.71–2.36) |
| Dementia | 0.92 (0.62–1.38) | 0.89 (0.60–1.34) | 0.82 (0.55–1.23) |
| Malignancy | 1.28 (1.02–1.60) | 1.06 (0.85–1.34) | 0.94 (0.74–1.20) |
| Alcohol abuse | 2.18 (1.51–3.15) | 1.59 (1.08–2.35) | 1.55 (1.05–2.28) |
| Pulmonary disease | 1.21 (0.97–1.50) | 1.05 (0.84–1.31) | 0.95 (0.75–1.19) |
| Rheumatic disease | 1.70 (1.31–2.21) | 1.40 (1.07–1.83) | 1.30 (0.99–1.71) |
| Gastrointestinal disease | 1.58 (1.33–1.87) | 1.10 (0.92–1.33) | 1.02 (0.84–1.24) |
| Charlson comorbidity index | |||
| 0 | 1.00 | NA | 1.00 |
| 1–3 | 1.74 (1.46–2.07) | NA | 1.32 (1.06–1.65) |
| 4–9 | 3.14 (2.08–4.74) | NA | 1.66 (0.99–2.76) |
| Number of drugs | |||
| 1–4 | 1.00 | NA | 1.00 |
| 5–9 | 1.82 (1.30–2.55) | NA | 1.56 (1.10–2.20) |
| 10–14 | 2.16 (1.53–3.06) | NA | 1.57 (1.06–2.31) |
| ≥15 | 3.14 (2.20–4.50) | NA | 1.88 (1.20–2.93) |
| Exposure to interacting drugs | |||
| Drugs with dynamic mechanism of interaction | 1.63 (1.38–1.93) | 1.43 (1.20–1.71) | 1.32 (1.10–1.59) |
| Drugs with kinetic mechanism of interaction | 1.01 (0.63–1.61) | 0.94 (0.59–1.52) | 0.90 (0.56–1.44) |
| Drugs with unclear mechanism of interaction | 1.10 (0.91–1.34) | 1.10 (0.90–1.33) | 1.05 (1.05–2.28) |
Notes: History of bleeding during 1 day<180 days before warfarin initiation treated as a stratifying variable.
a
Mutually adjusted for all variables except for Charlson comorbidity index and number of drugs;
b
mutually adjusted for all variables.
Abbreviations: CI, confidence interval; HR, hazard ratio; NA, not applicable.