Background
Methods
Study design
Data source
Study populations and exposure
Outcomes and follow-up
Covariates
Statistical methods
Quantitative bias analysis
Sensitivity analyses
Sensitivity analysis | Justification |
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1. In addition to the covariates identified by DAG, we included other covariates based on prior evidence of likely confounders such as chronic obstructive pulmonary disease, other respiratory diseases, cancer, immunosuppression, chronic kidney disease, general practice attendance rate in the year prior to cohort entry, and A&E attendance rate in the year prior to cohort entry in the fully adjusted models (stratified by general practice) | To test the robustness of the covariate selection |
2. Additionally adjusted for ethnicity in DAG and fully adjusted models. In the fully adjusted models, additional covariates included chronic obstructive pulmonary disease, other respiratory diseases (not including asthma), cancer, immunosuppression, chronic kidney disease, General Practice attendance rate in the year prior to cohort entry, and Accident and Emergency attendance rate in the year prior to cohort entry | In the main analysis, we did not adjust for ethnicity as a sizable proportion of individuals with missing ethnicity (~23%). We undertook complete case analysis to address missing data |
3. Repeated main analysis excluding people prescribed antiplatelets 4 months before study start date | To explore the impact of use of antiplatelet which can reduce the risk of blood clots |
4. Repeated main analysis excluding people who were prescribed both warfarin and DOACs on the day of the latest OAC prescription | To assess the sensitivity of exposure definition |
5. Repeated main analysis excluding people who ever had warfarin prescription 4 months before study start date in the DOAC group | As warfarin is hypothesised to have harmful effect on severe COVID-19 compared with DOAC, this analysis was to assess the sensitivity of exposure definition |
6. Time-updated the OAC exposure variable | To evaluate the impact of national recommendation on drug switching from warfarin to DOACs due to COVID-19 pandemic [24] |
Role of the funding source
Results
Current use of direct oral anticoagulant | Current use of warfarin | |
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Total | 280,407 | 92,339 |
Age as of 1 Mar 2020 | ||
18– < 40 | 510 (0.2) | 112 (0.1) |
40– < 50 | 2320 (0.8) | 361 (0.4) |
50– < 60 | 12,788 (4.6) | 2245 (2.4) |
60– < 70 | 42,407 (15.1) | 9824 (10.6) |
70– < 80 | 98,848 (35.3) | 34,051 (36.9) |
80+ | 123,534 (44.1) | 45,746 (49.5) |
Median, IQR | 78 (71–84) | 79 (73–85) |
Sex | ||
Female | 122,778 (43.8) | 36,414 (39.4) |
Body mass index | ||
< 18.5 | 5437 (1.9) | 1199 (1.3) |
18.5–24.9 | 72,658 (25.9) | 21,998 (23.8) |
25–29.9 | 94,621 (33.7) | 31,981 (34.6) |
30–34.9 | 57,590 (20.5) | 19,592 (21.2) |
35–39.9 | 24,032 (8.6) | 8114 (8.8) |
40+ | 12,586 (4.5) | 4539 (4.9) |
Missing | 13,483 (4.8) | 4916 (5.3) |
Ethnicity | ||
White | 201,046 (71.7) | 66,800 (72.3) |
Mixed | 548 (0.2) | 115 (0.1) |
Asian/Asian British | 3911 (1.4) | 766 (0.8) |
Black | 1289 (0.5) | 258 (0.3) |
Other | 1100 (0.4) | 281 (0.3) |
Missing | 72,513 (25.9) | 24,119 (26.1) |
Index of multiple deprivation | ||
1 (least deprived) | 57,570 (20.5) | 17,703 (19.2) |
2 | 56,881 (20.3) | 18,400 (19.9) |
3 | 55,654 (19.8) | 19,056 (20.6) |
4 | 54,758 (19.5) | 18,615 (20.2) |
5 (most deprived) | 55,544 (19.8) | 18,565 (20.1) |
Smoking status | ||
Never | 101,492 (36.2) | 33,005 (35.7) |
Former | 161,752 (57.7) | 54,463 (59.0) |
Current | 16,828 (6.0) | 4834 (5.2) |
Missing | 335 (0.1) | 37 (0.0) |
Hazardous alcohol use | 28,375 (10.1) | 7819 (8.5) |
Care home residence | 8133 (2.9) | 1039 (1.1) |
Comorbidities | ||
Hypertension | 195,078 (69.6) | 66,888 (72.4) |
Heart failure | 71,427 (25.5) | 26,926 (29.2) |
Myocardial infarction | 31,911 (11.4) | 10,414 (11.3) |
Peripheral arterial disease | 14,273 (5.1) | 5091 (5.5) |
Stroke/transient ischaemic attack | 60,271 (21.5) | 18,470 (20.0) |
Venous thromboembolism | 19,927 (7.1) | 8202 (8.9) |
Diabetes | ||
Controlled (HbA1c < 58 mmols/mol) | 61,178 (21.8) | 23,893 (25.9) |
Uncontrolled (HbA1c ≥ 58 mmols/mol) | 22,672 (8.1) | 7696 (8.3) |
HbA1c not measured | 838 (0.3) | 298 (0.3) |
COPD | 36,189 (12.9) | 11,272 (12.2) |
Other respiratory diseases | 16,444 (5.9) | 4731 (5.1) |
Cancer | 49,488 (17.6) | 16,240 (17.6) |
Immunosuppression | 1688 (0.6) | 528 (0.6) |
Chronic kidney disease | 95,715 (34.1) | 34,633 (37.5) |
Primary care consultations | ||
Median, IQR | 10 (6–17) | 16 (9–27) |
Min, Max | 0, 432 | 0, 307 |
A&E attendance | ||
Median, IQR | 0 (0–1) | 0 (0–1) |
Min, Max | 0, 69 | 0, 45 |
Flu vaccination | 220,153 (78.5) | 78,558 (85.1) |
Medications | ||
Oestrogen/oestrogen-like drugs | 1652 (0.6) | 361 (0.4) |
Antiplatelets | 19,030 (6.8) | 4108 (4.4) |