Abstract
Purpose
Methods
Results
Conclusions
Keywords
- •Direct oral anticoagulants with antiplatelets are associated with a similar risk of gastrointestinal bleeding compared with vitamin K antagonists and antiplatelets.
- •Direct oral anticoagulants with antiplatelets are associated with a decreased risk of intracranial hemorrhage and other major bleeding compared with vitamin K antagonists and antiplatelets.
- •There were no duration–response relations for the 3 bleeding outcomes.
- •Age, sex, or baseline bleeding risk did not modify the associations.
Background
Methods
Data Sources
Régie de l'assurance maladie Quebec (RAMQ). Public prescription drug insurance plan. Available at: http://www.ramq.gouv.qc.ca/en/citizens/prescription-drug-insurance/Pages/prescription-drug-insurance.aspx. Accessed March 9, 2018.
Base Cohort of Patients with Incident Nonvalvular Atrial Fibrillation
Study Cohort of Concomitant Oral Anticoagulant-Antiplatelet Users
Exposure Groups
Bleeding Outcomes
Disease Risk Score
Statistical Analysis
Secondary Analyses
Sensitivity Analyses
Results

Characteristic | Concomitant DOAC-Antiplatelet Use | Concomitant VKA-Antiplatelet Use |
---|---|---|
Total | 5301 | 9106 |
Age, y (mean, SD) | 75.5 (9.1) | 78.0 (9.0) |
Male, n (%) | 2819 (53.2) | 4709 (51.7) |
Time from NVAF diagnosis to VKA/DOAC initiation, d (mean, SD) | 77.0 (180.2) | 38.6 (116.3) |
History of alcohol-related disorders, n (%) | 210 (4.0) | 427 (4.7) |
History of arterial hypertension, n (%) | 4544 (85.7) | 8337 (91.6) |
History of cancer, n (%) | 787 (14.9) | 1399 (15.4) |
History of congestive heart failure, n (%) | 1043 (19.7) | 2804 (30.8) |
History of coronary artery disease, n (%) | 2577 (48.6) | 5588 (61.4) |
History of diabetes mellitus, n (%) | 1685 (31.8) | 3577 (39.3) |
History of liver disease, n (%) | 269 (5.1) | 676 (7.4) |
History of peripheral vascular disease, n (%) | 556 (10.5) | 1718 (18.9) |
Prior ischemic stroke or transient ischemic attack, n (%) | 486 (9.2) | 1105 (12.1) |
Prior major bleeding | 70 (1.3) | 171 (1.9) |
History of renal disease, n (%) | 457 (8.6) | 2210 (24.3) |
CHA2DS2-VASC score, mean (SD) | 3.7 (1.5) | 4.3 (1.5) |
Modified HAS-BLED score, mean (SD) | 1.4 (0.8) | 1.7 (1.0) |
Number of antiplatelets at cohort entry, mean (SD) | 1.1 (0.3) | 1.1 (0.4) |
One, n (%) | 4886 (92.2) | 7862 (86.3) |
Two or more, n (%) | 415 (7.8) | 1244 (13.7) |
Class of antiplatelets at cohort entry, n (%) | ||
Acetylsalicylic acid | 4972 (93.8) | 8487 (93.2) |
P2Y12 inhibitors | 744 (14.0) | 1863 (20.5) |
H2 blockers, n (%) | 85 (1.6) | 185 (2.0) |
Nonsteroidal anti-inflammatory drugs, n (%) | 947 (17.9) | 1527 (16.8) |
Proton pump inhibitors, n (%) | 2752 (51.9) | 5577 (61.3) |
Selective serotonin reuptake inhibitors, n (%) | 457 (8.6) | 901 (9.9) |
Number of non-antithrombotic drugs, mean (SD) | 11.5 (6.0) | 13.7 (6.6) |
Patients | Events | Person-Years | Incidence Rate (95% CI) | Rate Difference (95% CI) | Crude HR (95% CI) | Adjusted HR (95% CI) † Adjusted for disease risk score and calendar year. References: Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138:1093-1100. 18 Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137:263-272. 21 | |
---|---|---|---|---|---|---|---|
Intracranial hemorrhage | |||||||
Current concomitant VKA-antiplatelet use | 9106 | 54 | 3508 | 1.5 (1.2-2.0) | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 5301 | 11 | 1461 | 0.8 (0.4-1.4) | −0.3 (-1.6-1.1) | 0.47 (0.25-0.91) | 0.46 (0.24-0.91) |
Gastrointestinal bleeding | |||||||
Current concomitant VKA-antiplatelet use | 9106 | 181 | 3462 | 5.2 (4.5-6.1) | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 5301 | 72 | 1448 | 5.0 (3.9-6.3) | −0.8 (-1.4–0.2) | 0.87 (0.66-1.14) | 1.08 (0.81-1.45) |
Other major bleeding | |||||||
Current concomitant VKA-antiplatelet use | 9106 | 246 | 3421 | 7.2 (6.3-8.2) | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 5301 | 62 | 1450 | 4.3 (3.3-5.5) | −2.9 (-4.3–1.5) | 0.56 (0.43-0.74) | 0.68 (0.51-0.91) |
Type of Bleeding | ICD-10 Code | Description |
---|---|---|
ICH | I60 | Subarachnoid |
I61 | Intracerebral | |
I620 | Subdural | |
I621 | Nontraumatic extradural (acute) | |
I629 | Unspecified intracranial hemorrhage (nontraumatic) | |
I690 | Sequelae of subarachnoid hemorrhage | |
I691 | Sequelae of intracerebral hemorrhage | |
I692 | Sequelae of intracranial hemorrhage | |
S0636 | Traumatic hemorrhage of cerebrum | |
S064 | Epidural hemorrhage | |
S065 | Subdural (traumatic) | |
S066 | Subarachnoid (traumatic) | |
GIB | I850 | Esophageal varices with bleeding |
K920 | Hematemesis | |
K921 | Melena | |
K922 | Gastrointestinal hemorrhage (unspecified) | |
K226 | Gastro-esophageal laceration-hemorrhage syndrome | |
K228 | Hemorrhage of esophagus NOS | |
K250 | Acute gastric ulcer with hemorrhage | |
K252 | Acute gastric ulcer with hemorrhage/perforation | |
K254 | Chronic gastric ulcer with hemorrhage | |
K256 | Chronic gastric ulcer with hemorrhage/perforation | |
K260 | Acute duodenal ulcer with hemorrhage | |
K262 | Acute duodenal ulcer with hemorrhage/perforation | |
K264 | Chronic duodenal ulcer with hemorrhage | |
K266 | Chronic duodenal ulcer with hemorrhage/perforation | |
K270 | Acute peptic ulcer with hemorrhage | |
K272 | Acute peptic ulcer with hemorrhage/perforation | |
K274 | Chronic peptic ulcer with hemorrhage | |
K276 | Chronic peptic ulcer with hemorrhage/perforation | |
K280 | Acute gastrojejunal ulcer with hemorrhage | |
K282 | Acute gastrojejunal ulcer with hemorrhage/perforation | |
K284 | Chronic gastrojejunal ulcer with hemorrhage | |
K286 | Chronic gastrojejunal ulcer with hemorrhage/perforation | |
K290 | Acute hemorrhagic gastritis | |
K2921 | Alcoholic gastritis (with hemorrhage) | |
K2961 | Other gastritis with bleeding | |
K2971 | Gastritis (unspecified with bleeding) | |
K2991 | Gastroduodenitis (unspecified with bleeding) | |
K2981 | Duodenitis (with hemorrhage) | |
K3181 | Angiodysplasia of stomach and duodenum with hemorrhage | |
K5521 | Angiodysplasia of colon with hemorrhage | |
K5711 | Diverticulosis of small intestine without perforation or abscess with bleeding | |
K5713 | Diverticulitis of small intestine without perforation or abscess with bleeding | |
K5731 | Diverticulosis of large intestine without perforation or abscess with bleeding | |
K5733 | Diverticulitis of large intestine without perforation or abscess with bleeding | |
K625 | Hemorrhage of anus and rectum | |
K661 | Hemoperitoneum | |
Other | D683 | Hemorrhagic disorder due to circulating anticoagulants |
D699 | Unspecified hemorrhagic conditions | |
H0523 | Orbital hemorrhage | |
H113 | Conjunctival hemorrhage | |
H313 | Choroidal hemorrhage and rupture | |
H356 | Retinal hemorrhage | |
H431 | Vitreous hemorrhage | |
H44819 | Hemophthalmos, unspecified eye | |
H450 | Vitreous hemorrhage in diseases classified elsewhere | |
H922 | Otorrhagia | |
I230 | Hemopericardium as current complication following acute myocardial infarction | |
I312 | Hemopericardium NEC | |
J942 | Hemothorax | |
M250 | Hemarthrosis | |
M7981 | Nontraumatic hematoma of soft tissue | |
N02 | Recurrent and persistent hematuria | |
N421 | Congestion and hemorrhage of prostate | |
N836 | Hematosalpinx | |
N837 | Hematoma of broad ligament | |
N857 | Hematometra | |
N897 | Hematocolpos | |
N92 | Excessive, frequent and irregular menstruation | |
N93 | Other abnormal uterine and vaginal bleeding | |
N950 | Postmenopausal bleeding | |
R04 | Hemorrhage from respiratory passages | |
R31 | Unspecified hematuria | |
R233 | Spontaneous ecchymoses | |
R58 | Hemorrhage NEC | |
T810 | Hemorrhage and hematoma complicating a procedure NEC | |
T792 | Traumatic secondary and recurrent hemorrhage and seroma, initial encounter |
Type of Bleeding Event | |||
---|---|---|---|
Reasons for Censoring | Intracranial Hemorrhage | Gastrointestinal Bleeding | Other Major Bleeding |
Total number | 14,407 | 14,407 | 14,407 |
Discontinuation of concomitant use, n (%) | |||
DOAC/VKA | 2947 (20.5) | 2861 (19.9) | 2859 (19.8) |
Antiplatelet | 8591 (59.6) | 8529 (59.2) | 8518 (59.1) |
Both | 3 (0.02) | 3 (0.02) | 3 (0.02) |
Switch of use, n (%) | |||
From DOAC to VKA | 1 (0.01) | 1 (0.01) | 1 (0.01) |
From VKA to DOAC | 1 (0.01) | 1 (0.01) | 1 (0.01) |
End of registration, n (%) | 29 (0.2) | 28 (0.2) | 27 (0.2) |
Death, n (%) | 427 (3.0) | 424 (2.9) | 416 (2.9) |
End of study period, n (%) | 2136 (14.8) | 2108 (14.6) | 2084 (14.5) |
Exposure | Patients | Events | Person-Years | Incidence Rate (95% CI) | Crude HR (95% CI) | Adjusted HR (95% CI) |
---|---|---|---|---|---|---|
Intracranial hemorrhage | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 54 | 3508 | 1.5 (1.2-2.0) | [Reference] | [Reference] |
Current concomitant dabigatran-antiplatelet use | 2575 | 9 | 927 | 1.0 (0.4-1.8) | 0.63 (0.31-1.28) | 0.64 (0.32-1.30) |
Current concomitant rivaroxaban-antiplatelet use | 2207 | 1 | 446 | 0.2 (0.01-1.3) | 0.13 (0.02-0.97) | 0.12 (0.02-0.88) |
Current concomitant apixaban-antiplatelet use | 519 | 1 | 58 | 1.7 (0.04-9.6) | 0.90 (0.12-6.64) | 0.72 (0.09-5.61) |
Gastrointestinal bleeding | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 181 | 3462 | 5.2 (4.5-6.1) | [Reference] | [Reference] |
Current concomitant dabigatran-antiplatelet use | 2575 | 44 | 918 | 4.8 (3.5-6.4) | 0.91 (0.66-1.27) | 1.10 (0.79-1.54) |
Current concomitant rivaroxaban-antiplatelet use | 2207 | 26 | 442 | 5.9 (3.8-8.6) | 0.89 (0.59-1.35) | 1.18 (0.75-1.87) |
Current concomitant apixaban-antiplatelet use | 519 | 2 | 58 | 3.5 (0.4-12.5) | 0.45 (0.11-1.81) | 0.54 (0.13-2.24) |
Other major bleeding | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 246 | 3421 | 7.2 (6.3-8.2) | [Reference] | [Reference] |
Current concomitant dabigatran-antiplatelet use | 2575 | 30 | 922 | 3.3 (2.2-4.7) | 0.45 (0.31-0.66) | 0.54 (0.37-0.80) |
Current concomitant rivaroxaban-antiplatelet use | 2207 | 28 | 442 | 6.3 (4.2-9.2) | 0.77 (0.52-1.14) | 1.01 (0.66-1.56) |
Current concomitant apixaban-antiplatelet use | 519 | 4 | 58 | 6.9 (1.9-17.7) | 0.74 (0.28-2.01) | 0.96 (0.34-2.66) |
Exposure | < 3 Months HR (95% CI) | 3-5.9 Months HR (95% CI) | ≥6 Months HR (95% CI) | P for Interaction |
---|---|---|---|---|
Intracranial hemorrhage | ||||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 0.37 (0.15-0.92) | 0.35 (0.04-2.82) | 0.63 (0.22-1.87) | .73 |
Gastrointestinal bleeding | ||||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 1.09 (0.75-1.57) | 1.18 (0.61-2.29) | 0.90 (0.48-1.70) | .83 |
Other major bleeding | ||||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 0.67 (0.46-0.97) | 0.84 (0.43-1.64) | 0.62 (0.34-1.12) | .77 |
Exposure | ≤75 Years of Age HR (95% CI) | >75 Years of Age HR (95% CI) | P for Interaction |
---|---|---|---|
Intracranial hemorrhage | |||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 0.23 (0.05-0.99) | 0.63 (0.30-1.33) | .22 |
Gastrointestinal bleeding | |||
Current concomitant VKA-antiplatelet use | 1.00 [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 1.32 (0.86-2.04) | 0.94 (0.64-1.37) | .22 |
Other major bleeding | |||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 0.78 (0.52-1.18) | 0.61 (0.41-0.91) | .38 |
Exposure | Female HR (95% CI) | Male HR (95% CI) | P for Interaction |
---|---|---|---|
Intracranial hemorrhage | |||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 0.66 (0.24-1.80) | 0.37 (0.15-0.88) | .38 |
Gastrointestinal bleeding | |||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 1.34 (0.88-2.03) | 0.93 (0.63-1.36) | .19 |
Other major bleeding | |||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 0.53 (0.32-0.89) | 0.77 (0.54-1.09) | .24 |
Exposure | HAS-BLED Score 0-2 HR (95% CI) | HAS-BLED Score 3-7 HR (95% CI) | P for Interaction |
---|---|---|---|
Intracranial hemorrhage | |||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 0.62 (0.31-1.24) | – | .98 |
Gastrointestinal bleeding | |||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 1.25 (0.91-1.73) | 0.72 (0.36-1.46) | .16 |
Other major bleeding | |||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 0.68 (0.49-0.94) | 0.79 (0.42-1.49) | 0.69 |
Exposure | Patients | Events | Person-Years | Incidence Rate (95% CI) | Crude HR (95% CI) | Adjusted HR (95% CI) |
---|---|---|---|---|---|---|
Current concomitant VKA-antiplatelet use | 9106 | 59 | 3484 | 1.7 (1.3-2.2) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 29 | 1458 | 2.0 (1.3-2.9) | 1.15 (0.74-1.81) | 1.42 (0.88-2.27) |
DOAC types | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 59 | 3484 | 1.7 (1.3-2.2) | [Reference] | [Reference] |
Current concomitant dabigatran-antiplatelet use | 2575 | 14 | 925 | 1.5 (0.8-2.5) | 0.90 (0.50-1.62) | 1.04 (0.58-1.87) |
Current concomitant rivaroxaban-antiplatelet use | 2207 | 13 | 445 | 2.9 (1.6-5.0) | 1.67 (0.90-3.08) | 2.81 (1.35-5.81) |
Current concomitant apixaban-antiplatelet use | 519 | 2 | 58 | 3.4 (0.4-12.4) | 1.87 (0.45-7.81) | 3.57 (0.78-16.38) |
Exposure | Patients | Events | Person-Years | Incidence Rate (95% CI) | Crude HR (95% CI) | Adjusted HR (95% CI) |
---|---|---|---|---|---|---|
Intracranial hemorrhage | ||||||
Current concomitant VKA-ASA use | 7243 | 41 | 2568 | 1.6 (1.2-2.2) | [Reference] | [Reference] |
Current concomitant DOAC-ASA use | 4557 | 9 | 1181 | 0.8 (0.4-1.5) | 0.47 (0.23-0.97) | 0.47 (0.22-0.99) |
Gastrointestinal bleeding | ||||||
Current concomitant VKA-ASA use | 7243 | 121 | 2543 | 4.8 (4.0-5.7) | [Reference] | [Reference] |
Current concomitant DOAC-ASA use | 4557 | 54 | 1171 | 4.6 (3.5-6.0) | 0.89 (0.65-1.23) | 1.15 (0.82-1.62) |
Other major bleeding | ||||||
Current concomitant VKA-ASA use | 7243 | 155 | 2522 | 6.1 (5.2-7.2) | [Reference] | [Reference] |
Current concomitant DOAC-ASA use | 4557 | 48 | 1173 | 4.1 (3.0-5.4) | 0.63 (0.45-0.87) | 0.75 (0.54-1.06) |
Exposure | Patients | Events | Person-Years | Incidence Rate (95% CI) | Crude HR (95% CI) | Adjusted HR (95% CI) |
---|---|---|---|---|---|---|
Intracranial hemorrhage | ||||||
Current concomitant use of a VKA with multiple antiplatelets | 1244 | 8 | 767 | 1.0 (0.5-2.1) | [Reference] | [Reference] |
Current concomitant use of a DOAC with multiple antiplatelets | 415 | 0 | 209 | - | - | - |
Gastrointestinal bleeding | ||||||
Current concomitant use of a VKA with multiple antiplatelets | 1244 | 52 | 749 | 7.0 (5.2-9.1) | [Reference] | [Reference] |
Current concomitant use of a DOAC with multiple antiplatelets | 415 | 16 | 206 | 7.8 (4.4-12.6) | 1.04 (0.59-1.82) | 1.13 (0.63-2.04) |
Other major bleeding | ||||||
Current concomitant use of a VKA with multiple antiplatelets | 1244 | 76 | 737 | 10.3 (8.1-12.9) | [Reference] | [Reference] |
Current concomitant use of a DOAC with multiple antiplatelets | 415 | 11 | 208 | 5.3 (2.6-9.5) | 0.49 (0.26-0.93) | 0.56 (0.29-1.07) |
Exposure | Addition of Antiplatelets HR (95% CI) | Addition of an Oral Anticoagulant HR (95% CI) | Concomitant Initiation of an Oral Anticoagulant and Antiplatelets HR (95% CI) | P for Interaction |
---|---|---|---|---|
Intracranial hemorrhage | ||||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 0.61 (0.06-5.85) | 0.46 (0.23-0.92) | – | .97 |
Gastrointestinal bleeding | ||||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 1.66 (0.44-6.22) | 1.03 (0.76-1.40) | 1.65 (0.54-5.06) | .58 |
Other major bleeding | ||||
Current concomitant VKA-antiplatelet use | [Reference] | [Reference] | [Reference] | |
Current concomitant DOAC-antiplatelet use | 1.96 (0.65-5.87) | 0.63 (0.46-0.86) | 0.78 (0.23-2.62) | .14 |





Exposure | Patients | Events | Person-Years | Incidence Rate (95% CI) | Crude HR (95% CI) | Adjusted HR (95% CI) |
---|---|---|---|---|---|---|
Intracranial hemorrhage | ||||||
Current concomitant VKA-antiplatelet use | 8814 | 40 | 2568 | 1.6 (1.1-2.2) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5144 | 7 | 1157 | 0.6 (0.2-1.3) | 0.39 (0.18-0.88) | 0.39 (0.17-0.89) |
Gastrointestinal bleeding | ||||||
Current concomitant VKA-antiplatelet use | 8814 | 147 | 2541 | 5.8 (4.9-6.8) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5144 | 58 | 1148 | 5.1 (3.8-6.5) | 0.82 (0.60-1.11) | 1.02 (0.74-1.40) |
Other major bleeding | ||||||
Current concomitant VKA-antiplatelet use | 8814 | 187 | 2517 | 7.4 (6.4-8.6) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5144 | 47 | 1151 | 4.1 (3.0-5.4) | 0.52 (0.38-0.72) | 0.61 (0.44-0.86) |
Exposure | Patients | Events | Person-Years | Incidence Rate (95% CI) | Crude HR (95% CI) | Adjusted HR (95% CI) |
---|---|---|---|---|---|---|
Intracranial hemorrhage | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 40 | 3508 | 1.1 (0.8-1.6) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 9 | 1461 | 0.6 (0.3-1.2) | 0.51 (0.25-1.06) | 0.47 (0.22-0.99) |
Gastrointestinal bleeding | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 74 | 3488 | 2.1 (1.7-3.3) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 34 | 1457 | 2.3 (1.6-3.3) | 1.00 (0.66-1.50) | 1.21 (0.79-1.85) |
Other major bleeding | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 77 | 3481 | 2.2 (1.8-2.8) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 13 | 1461 | 0.9 (0.5-1.5) | 0.39 (0.22-0.70) | 0.42 (0.23-0.78) |
Exposure | Patients | Events | Person-Years | Incidence Rate (95% CI) | Crude HR (95% CI) | Adjusted HR (95% CI) |
---|---|---|---|---|---|---|
Intracranial hemorrhage | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 91 | 7579 | 1.2 (1.0-1.5) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 24 | 3763 | 0.6 (0.4-1.0) | 0.53 (0.34-0.83) | 0.58 (0.36-0.93) |
Gastrointestinal bleeding | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 266 | 7477 | 3.6 (3.1-4.0) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 115 | 3717 | 3.1 (2.6-3.7) | 0.84 (0.68-1.05) | 1.05 (0.83-1.33) |
Other major bleeding | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 385 | 7422 | 5.2 (4.7-5.7) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 108 | 3722 | 2.9 (2.4-3.5) | 0.54 (0.44-0.67) | 0.67 (0.54-0.84) |
Exposure | Patients | Events | Person-Years | Incidence Rate (95% CI) | Crude HR (95% CI) | Adjusted HR (95% CI) |
---|---|---|---|---|---|---|
Intracranial hemorrhage | ||||||
Current concomitant VKA-antiplatelet use | 9092 | 54 | 3503 | 1.5 (1.2-2.0) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5248 | 11 | 1444 | 0.8 (0.4-1.4) | 0.48 (0.25-0.92) | 0.47 (0.24-0.91) |
Gastrointestinal bleeding | ||||||
Current concomitant VKA-antiplatelet use | 9092 | 180 | 3458 | 5.2 (4.5-6.0) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5248 | 70 | 1432 | 4.9 (3.8-6.2) | 0.85 (0.65-1.13) | 1.08 (0.81-1.45) |
Other major bleeding | ||||||
Current concomitant VKA-antiplatelet use | 9092 | 245 | 3416 | 7.2 (6.3-8.1) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5248 | 61 | 1433 | 4.3 (3.3-5.5) | 0.56 (0.42-0.74) | 0.68 (0.51-0.91) |
Exposure | Patients | Events | Person-Years | Incidence Rate (95% CI) | Crude HR (95% CI) | Adjusted HR (95% CI) |
---|---|---|---|---|---|---|
Intracranial hemorrhage | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 54 | 3508 | 1.5 (1.2-2.0) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 11 | 1461 | 0.8 (0.4-1.4) | 0.48 (0.25-0.92) | 0.47 (0.24-0.93) |
Gastrointestinal bleeding | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 181 | 3462 | 5.2 (4.5-6.1) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 72 | 1448 | 5.0 (3.9-6.3) | 0.88 (0.67-1.15) | 1.09 (0.82-1.45) |
Other major bleeding | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 246 | 3421 | 7.2 (6.3-8.2) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 62 | 1450 | 4.3 (3.3-5.5) | 0.57 (0.43-0.75) | 0.69 (0.52-0.92) |
Exposure | Patients | Events | Person-Years | Incidence Rate (95% CI) | Crude HR (95% CI) | Adjusted HR (95% CI) |
---|---|---|---|---|---|---|
Intracranial hemorrhage | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 51 | 3378 | 1.5 (1.1-2.0) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 11 | 1438 | 0.8 (0.4-1.4) | 0.49 (0.25-0.94) | 0.49 (0.25-0.96) |
Gastrointestinal bleeding | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 178 | 3378 | 5.3 (4.5-6.1) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 70 | 1438 | 4.9 (3.8-6.2) | 0.85 (0.64-1.12) | 1.05 (0.78-1.41) |
Other major bleeding | ||||||
Current concomitant VKA-antiplatelet use | 9106 | 240 | 3378 | 7.1 (6.2-8.1) | [Reference] | [Reference] |
Current concomitant DOAC-antiplatelet use | 5301 | 61 | 1438 | 4.2 (3.2-5.5) | 0.57 (0.43-0.75) | 0.68 (0.51-0.91) |
Discussion
ClinicalTrials.gov. NIH U.S. National Library of Medicine. A study of apixaban in patients with atrial fibrillation, not caused by a heart valve problem, who are at risk for thrombosis (blood clots) due to having had a recent coronary event, such as a heart attack or a procedure to open the vessels of the heart. Available at: https://clinicaltrials.gov/ct2/show/NCT02415400. Accessed April 9, 2018.
Acknowledgments
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Article info
Publication history
Footnotes
Funding: This work was supported, in part, by an infrastructure grant from the Canadian Foundation for Innovation (CFI), and the dataset was acquired thanks to unrestricted funding from Bayer Pharma AG. The sponsors had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Conflict of Interest: SS has received research grants from Bayer Pharma AG, Boehringer Ingelheim, and Bristol-Myers-Squibb, and has participated in advisory board meetings or as speaker for AstraZeneca, Boehringer Ingelheim, and Novartis. AD, CR, HY, KBF, and LA have no conflicts of interest to disclose.
Authorship: LA had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.