Background
Methods
Data source
Study population
Endpoints and follow-up
Treatment classification
Statistical analysis
Stroke population after matching | VKA (n = 347,240) | DOAC (n = 347,240) | SMD | ||
---|---|---|---|---|---|
Before | After | ||||
Age | Mean(± SD) | 75.78 (± 8.84) | 75.70 (± 9.85) | 0.03 | 0.01 |
Median | 77 | 77 | |||
Age distribution (%) | 18–36 | 0.09 | 0.19 | ||
37–54 | 2.14 | 3.22 | |||
55–72 | 27.53 | 27.43 | |||
73+ | 70.24 | 69.16 | |||
Female sex (%) | 52.02 | 53.00 | − 0.07 | − 0.02 | |
CHA2DS2-VASc score | Mean (± SD) | 4.45 (± 1.70) | 4.39 (± 1.77) | 0.12 | 0.04 |
Median | 4 | 4 | |||
CHA2DS2-VASc score distribution (%) | 0–1 | 3.77 | 5.29 | ||
2–3 | 25.12 | 25.28 | |||
4–5 | 44.74 | 43.23 | |||
6–7 | 22.41 | 22.02 | |||
8–9 | 3.96 | 4.18 | |||
Charlson Comorbidity Index | Mean (± SD) | 2.92 (± 2.63) | 2.84 (± 2.63) | 0.09 | 0.03 |
Median | 2 | 2 | |||
Charlson Comorbidity Index distribution (%) | 0–4 | 76.76 | 77.66 | ||
5–9 | 20.91 | 20.03 | |||
10–15 | 2.24 | 2.24 | |||
15+ | 0.16 | 0.14 | |||
Number of distinct prescriptions (ATCs) | Mean (± SD) | 12.50 (± 5.72) | 12.43 (± 5.78) | 0.05 | 0.01 |
Median | 12 | 11 | |||
Number of prescriptions (ATCs) | Mean (± SD) | 35.43 (± 21.17) | 34.88 (± 21.43) | 0.08 | 0.03 |
Median | 31 | 30 | |||
Number of diagnoses (ICD codes) | Mean (± SD) | 28.21 (± 15.39) | 27.97 (± 15.52) | 0.04 | 0.02 |
Median | 26 | 25 | |||
Prescribed medicines (%) | Antiarrhythmic agents | 90.47 | 90.41 | 0.01 | 0.00 |
Antihypertensive drugs | 80.94 | 80.39 | 0.06 | 0.01 | |
Antiplatelet drugs | 25.14 | 25.56 | − 0.03 | − 0.01 | |
Corticosteroids (systemic use) | 14.83 | 15.09 | − 0.03 | − 0.01 | |
Fondaparinux | 0.78 | 0.68 | 0.02 | 0.01 | |
Heparins | 27.02 | 23.44 | 0.36 | 0.07 | |
Insulin | 10.98 | 10.57 | 0.04 | 0.01 | |
Lipid-lowering agents | 47.61 | 46.35 | 0.09 | 0.03 | |
NSAIDs | 40.00 | 40.79 | − 0.05 | − 0.02 | |
Oral anti-diabetic drugs | 20.12 | 20.09 | 0.01 | 0.00 | |
Peptic ulcer/reflux disease | 49.88 | 50.32 | − 0.04 | − 0.01 | |
SSRIs | 5.39 | 5.62 | − 0.04 | − 0.01 | |
Comorbidities (%) | Alcohol abuse/addiction | 2.33 | 2.42 | − 0.02 | − 0.01 |
Bleeding extracerebral | 5.53 | 5.11 | 0.05 | 0.02 | |
Bleeding GI | 5.81 | 5.68 | 0.02 | 0.01 | |
Bleeding intracerebral | 0.45 | 0.48 | − 0.02 | 0.00 | |
Cancer | 19.77 | 19.80 | 0.00 | 0.00 | |
Coagulopathy | 1.81 | 1.63 | 0.03 | 0.01 | |
Congestive heart failure | 28.97 | 27.18 | 0.12 | 0.04 | |
COPD | 16.04 | 15.79 | 0.02 | 0.01 | |
Coronary heart disease | 40.67 | 38.72 | 0.13 | 0.04 | |
Diabetes | 38.69 | 37.84 | 0.05 | 0.02 | |
Diverticulitis | 10.66 | 10.80 | − 0.01 | 0.00 | |
Embolism systemic | 0.80 | 0.70 | 0.03 | 0.01 | |
Embolism venous | 5.15 | 4.75 | 0.05 | 0.02 | |
Esophageal varices | 0.21 | 0.21 | 0.00 | 0.00 | |
Hypertension | 88.14 | 87.79 | 0.05 | 0.01 | |
Ischemic stroke | 8.62 | 8.41 | 0.02 | 0.01 | |
Liver disease | 13.48 | 13.31 | 0.02 | 0.00 | |
Nicotine use/dependence | 4.44 | 4.51 | − 0.01 | 0.00 | |
Renal disease | 14.88 | 13.31 | 0.12 | 0.04 | |
Upper GI | 25.97 | 26.25 | − 0.03 | − 0.01 | |
Vascular disease | 21.99 | 21.54 | 0.04 | 0.01 | |
Vascular dementia | 1.87 | 1.99 | − 0.05 | − 0.01 | |
Venous malformation | 1.85 | 1.64 | 0.04 | 0.02 |
Sensitivity analysis
Results
Number of patients before matching | |||||||
VKA | DOAC | Dabigatran | Rivaroxaban | Apixaban | Edoxaban | ||
Study population | Stroke | 405,437 | 430,940 | 53,057 | 228,609 | 131,751 | 14,276 |
Embolism | 404,823 | 431,816 | 52,796 | 228,522 | 132,872 | 14,556 | |
TIA | 405,012 | 431,574 | 52,839 | 228,593 | 132,547 | 14,442 | |
Bleeding | 408,402 | 427,477 | 53,233 | 229,934 | 127,613 | 13,266 | |
Mortality | 404,695 | 431,978 | 52,763 | 228,499 | 133,059 | 14,586 | |
Number of patients after matching | |||||||
VKA | DOAC | Dabigatran* | Rivaroxaban* | Apixaban* | Edoxaban* | ||
Study population | Stroke | 347,240 | 347,240 | 53,057 | 228,600 | 131,748 | 14,276 |
Embolism | 347,297 | 347,297 | 52,796 | 228,513 | 132,869 | 14,556 | |
TIA | 347,247 | 347,247 | 52,839 | 228,584 | 132,544 | 14,442 | |
Bleeding | 346,343 | 346,343 | 53,233 | 229,926 | 127,610 | 13,266 | |
Mortality | 347,351 | 347,351 | 52,763 | 228,490 | 133,056 | 14,586 |
Events | Incidence rate per 1000 PY | Adjusted HR (95% CI) | p value | |
---|---|---|---|---|
VKA | DOAC | |||
Stroke | 26.69 | 33.45 | 1.32 (1.29–1.35) | < .001 |
TIA | 11.16 | 11.71 | 1.10 (1.06–1.14) | < .001 |
Embolism (systemic) | 4.01 | 2.99 | 0.78 (0.73–0.83) | < .001 |
Bleeding | 136.57 | 117.7 | 0.89 (0.88–0.90) | < .001 |
Mortality (all cause) | 61.36 | 73.5 | – | – |
Events | Incidence rate per 1000 PY | Adjusted HR (95% CI) | p value | |
---|---|---|---|---|
VKA | Dabigatran | |||
Stroke | 26.77 | 45.94 | 1.93 (1.82–2.03) | < .001 |
TIA | 11.64 | 14.13 | 1.33 (1.22–1.45) | < .001 |
Embolism (systemic) | 3.69 | 3.07 | 0.93 (0.79–1.10) | .42 |
Bleeding | 134.82 | 107.77 | 0.85 (0.83–0.88) | < .001 |
Mortality (all cause) | 52.34 | 63.49 | – | – |
VKA | Rivaroxaban | |||
Stroke | 25.88 | 27.77 | 1.13 (1.10–1.17) | < .001 |
TIA | 10.69 | 10.83 | 1.06 (1.01–1.11) | .02 |
Embolism (systemic) | 3.79 | 2.99 | 0.83 (0.77–0.90) | < .001 |
Bleeding | 135.19 | 133.23 | 1.03 (1.01–1.04) | < .001 |
Mortality (all cause) | 57.79 | 75.02 | – | – |
VKA | Apixaban | |||
Stroke | 27.58 | 38.81 | 1.52 (1.46–1.58) | < .001 |
TIA | 11.58 | 12.33 | 1.15 (1.08–1.22) | < .001 |
Embolism (systemic) | 3.77 | 2.75 | 0.75 (0.67–0.85) | < .001 |
Bleeding | 137.8 | 93.36 | 0.71 (0.70–0.73) | < .001 |
Mortality (all cause) | 64.26 | 74.45 | – | – |
VKA | Edoxaban | |||
Stroke | 26.24 | 15.53 | 0.88 (0.74–1.05) | .16 |
TIA | 11.18 | 5.18 | 0.71 (0.53–0.95) | .02 |
Embolism (systemic) | 3.94 | 1.31 | 0.29 (0.17–0.51) | < .001 |
Bleeding | 133.92 | 69.82 | 0.74 (0.68–0.81) | < .001 |
Mortality (all cause) | 53.58 | 30.62 | – | – |