Table 4.
Risk of bleeding associated with type of antidepressant in atrial fibrillation patients taking oral anticoagulants in PS-matched cohorts, stratified by sex, age, and oral anticoagulation type, MarketScan®, 2007–2015
| Hazard ratio (95% confidence interval)a | |||
|---|---|---|---|
| SSRI vs SNRI | SSRI vs SRI | SSRI vs TCA | |
| Warfarin | 1.23 (0.96 to 1.59) | 1.11 (0.89 to 1.37) | 1.06 (0.85 to 1.35) |
| DOAC | 1.10 (0.56 to 2.13) | 1.03 (0.54 to 2.00) | 1.18 (0.40 to 3.45) |
| P for multiplicative interaction | 0.92 | 0.86 | 0.42 |
| RERI (95% confidence interval) | − 0.07 (− 0.81 to 0.67) | − 0.06 (− 0.61 to 0.49) | − 0.69 (− 1.23 to − 0.15) |
| P for additive interaction | 0.85 | 0.83 | 0.01 |
| Male | 1.39 (0.99 to 1.39) | 1.09 (0.83 to 1.43) | 1.14 (0.83 to 1.56) |
| Female | 1.08 (0.77 to 1.49) | 1.10 (0.80 to 1.49) | 0.96 (0.69 to 1.33) |
| P for multiplicative interaction | 0.31 | 0.94 | 0.45 |
| RERI (95% confidence interval) | 0.24 (− 0.27 to 0.74) | 0.02 (− 0.37 to 0.41) | 0.15 (− 0.40 to 0.70) |
| P for additive interaction | 0.36 | 0.92 | 0.60 |
| Age > 75 years | 1.30 (0.95 to 1.79) | 1.32 (1.02 to 1.69) | 1.20 (0.91 to 1.59) |
| Age ≤ 75 years | 1.14 (0.79 to 1.61) | 0.79 (0.56 to 1.12) | 0.81 (0.55 to 1.18) |
| P for multiplicative interaction | 0.66 | 0.02 | 0.10 |
| RERI (95% confidence interval) | 0.16(− 0.28 to 0.60) | 0.44 (− 0.20 to 1.08) | 0.37 (− 0.23 to 0.97) |
| P for additive interaction | 0.47 | 0.18 | 0.22 |
| SNRI vs TCA | SNRI vs SRI | SRI vs TCA | |
|---|---|---|---|
| Warfarin | 0.95 (0.72 to 1.23) | 0.85 (0.65 to 1.11) | 1.00 (0.79 to 1.28) |
| DOAC | 1.85 (0.72 to 4.76) | 1.12 (0.54 to 2.32) | 1.28 (0.56 to 3.03) |
| P for multiplicative interaction | 0.37 | 0.55 | 0.43 |
| RERI (95% confidence interval) | 0.48 (− 0.30 to 1.25) | 0.21 (− 0.46 to 0.88) | 0.42 (− 0.22 to 1.09) |
| P for additive interaction | 0.23 | 0.54 | 0.22 |
| Male | 1.08 (0.74 to 1.56) | 0.84 (0.58 to 1.20) | 1.16 (0.84 to 1.61) |
| Female | 0.94 (0.65 to 1.30) | 0.88 (0.62 to 1.27) | 0.93 (0.66 to 1.30) |
| P for multiplicative interaction | 0.51 | 0.68 | 0.41 |
| RERI (95% Confidence Interval) | 0.16 (− 0.39 to 0.72) | − 0.08 (− 0.56 to 0.39) | 0.20 (− 0.28 to 0.69) |
| p for additive interaction | 0.57 | 0.73 | 0.41 |
| Age > 75 years | 0.96 (0.68 to 1.35) | 1.00 (0.71 to 1.41) | 0.96 (0.70 to 1.30) |
| Age ≤ 75 years | 1.01 (0.69 to 1.49) | 0.70 (0.48 to 1.01) | 1.19 (0.83 to 1.69) |
| P for multiplicative interaction | 0.72 | 0.16 | 0.35 |
| RERI (95% confidence interval) | − 0.12 (− 0.56 to 0.33) | 0.30 (− 0.03 to 0.64) | − 0.26 (− 0.63 to 0.12) |
| P for additive interaction | 0.61 | 0.07 | 0.18 |
DOAC direct oral anticoagulant, PS propensity score, RERI relative excess risk due to Interaction, SNRI serotonin/norepinephrine reuptake inhibitor, SRI serotonin reuptake inhibitor, SSRI selective serotonin reuptake inhibitor, TCA tricyclic antidepressant
aAll models corresponded to pairwise PS-matched cohorts. Models were adjusted for age, sex, HAS-BLED score, CHA2DS2-VASc score, alcohol use, comorbid conditions (heart failure, hypertension, diabetes, myocardial infarction, peripheral artery disease, kidney failure, stroke, bleeding, anemia, coagulopathy, cancer, mood disorder, cognitive impairment, chronic obstructive pulmonary disease, and liver disease) and other medications (antiplatelet, diuretic drugs, antiarrhythmic drugs, digoxin, angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, and lipid-lowering medications)