Table 1. Baseline Characteristics of Critically Ill Participantsa.
| Characteristics | Aspirin (n = 565) | P2Y12 inhibitors (n = 455) | Control (n = 529)b |
|---|---|---|---|
| Age, median (IQR), y | 57.0 (48.0-64.0) | 57.0 (49.0-65.0) | 57.0 (48.0-63.0) |
| Sex, No. (%) | |||
| Female | 199 (35.2) | 139 (30.5) | 183 (34.6) |
| Male | 366 (64.8) | 316 (69.5) | 346 (65.4) |
| Race and ethnicity, No./total (%)c | |||
| Asian | 46/460 (10.0) | 36/372 (9.7) | 58/419 (13.8) |
| Black | 16/460 (3.5) | 9/372 (2.4) | 16/419 (3.8) |
| Multiracial | 19/460 (4.1) | 5/372 (1.3) | 10/419 (2.4) |
| White | 352/460 (76.5) | 307/372 (82.5) | 309/419 (73.7) |
| Other | 27/460 (5.9) | 15/372 (4.0) | 26/419 (6.2) |
| Body mass index, median (IQR)d | 31.7 (27.4-37.6) | 31.3 (26.9-37.2) | 31.1 (27.0-35.9) |
| APACHE II score, median (IQR)e | 12.0 (8.0-17.0) | 12.0 (8.0-18.0) | 12.0 (8.0-17.0) |
| Confirmed SARS-CoV-2 infection, No./total (%)f | 505/519 (97.3) | 400/415 (96.4) | 465/477 (97.5) |
| Preexisting condition, No./total (%)g | |||
| Diabetes | 134/562 (23.8) | 93/449 (20.7) | 112/521 (21.5) |
| Respiratory disease | 113/562 (20.1) | 88/449 (19.6) | 97/522 (18.6) |
| Kidney disease | 16/528 (3.0) | 18/416 (4.3) | 18/485 (3.7) |
| Severe cardiovascular disease | 18/552 (3.3) | 23/437 (5.3) | 26/517 (5.0) |
| Any immunosuppressive condition | 23/562 (4.1) | 19/449 (4.2) | 23/522 (4.4) |
| Time to enrollment, median (IQR) | |||
| From hospital admission, d | 1.5 (0.9-3.0) | 1.8 (1.0-3.5) | 1.8 (0.9-3.7) |
| From intensive care unit admission, h | 17.2 (9.8-22.4) | 17.9 (12.0-23.5) | 18.2 (10.7-23.9) |
| Acute respiratory support, No. (%) | |||
| Invasive mechanical ventilation | 213 (37.7) | 161 (35.4) | 194 (36.7) |
| Noninvasive ventilation only | 227 (40.2) | 173 (38.0) | 202 (38.2) |
| High-flow nasal cannula | 125 (22.1) | 121 (26.6) | 132 (25.0) |
| None/supplemental oxygen | 0 | 0 | 1 (0.2) |
| Pao2/Fio2, median (IQR) | 115 (86-148) [n = 537] | 118 (90-163) [n = 430] | 113 (89-147) [n = 495] |
| Vasopressor support, No. (%) | 121 (21.4) | 72 (15.8) | 88 (16.6) |
| Laboratory values, median (IQR)h | |||
| C-reactive protein, μg/mL | 118 (62-180) [n = 486] | 109 (59-179) [n = 411] | 113 (60-180) [n = 452] |
| D-dimer, μg/mL | 972 (500-2599) [n = 334] | 850 (386-2297) [n = 279] | 898 (490-2705) [n = 307] |
| D-dimer ratioi | 2.5 (1.3-7.6) [n = 213] | 2.1 (1.3-5.1) [n = 60] | 2.2 (1.3-6.6) [n = 234] |
| Platelet count, ×109/L | 251 (194-313) [n = 547] | 239 (184-312) [n = 444] | 253 (196-327) [n = 513] |
| Concomitant therapies within 48 h of randomization, No./total (%) | |||
| Steroids | 552/562 (98.2) | 433/448 (96.7) | 511/521 (98.1) |
| Remdesivir | 113/562 (20.1) | 87/448 (19.4) | 126/521 (24.2) |
| Tocilizumab | 248/562 (44.1) | 201/448 (44.9) | 217/521 (41.7) |
| Sarilumab | 66/562 (11.7) | 45/448 (10.0) | 54/521 (10.4) |
| Concurrent anticoagulant type, No./total (%) | |||
| Low-molecular-weight heparin | 512/522 (98.1) | 395/408 (96.8) | 480/489 (98.2) |
| Unfractionated heparin | 8/522 (1.5) | 8/408 (2.0) | 8/489 (1.6) |
| Direct oral anticoagulants | 2/522 (0.4) | 5/408 (1.2) | 1/489 (0.2) |
| Anticoagulant dose, No. (%) | |||
| Low prophylactic | 112 (19.8) | 87 (19.1) | 75 (14.2) |
| Intermediate prophylactic | 312 (55.2) | 214 (47.0) | 312 (59.0) |
| Subtherapeutic | 22 (3.9) | 21 (4.6) | 24 (4.5) |
| Therapeutic | 54 (9.6) | 65 (14.3) | 56 (10.6) |
| Unknown | 65 (11.5) | 68 (14.9) | 62 (11.7) |
Abbreviation: Pao2/Fio2, ratio of partial pressure of arterial oxygen to fraction of inspired oxygen.
Percentages may not sum to 100 because of rounding.
The control group include all patients randomized to control who were also eligible to be randomized to an antiplatelet agent.
Data collection was not approved in Asia, Canada, and continental Europe. “Other” includes Māori, Aboriginal, Pacific Islander, and “other ethnic group.” Participants (or their surrogates) self-reported their race and ethnicity via fixed categories appropriate to their region. A patient may decline to provide their race or ethnicity at the time of registration, and the person performing the registration may decline to ask the patient to clarify race or ethnicity at the time of registration.
Body mass index is calculated as weight in kilograms divided by the square of height in meters.
The Acute Physiology and Chronic Health Evaluation (APACHE) II measures severity of illness based on age, medical history, and physiologic variables. The score ranges from 0 to 71, with higher scores indicating more severe disease and a higher risk of death; eg, an APACHE II score of 12 indicates a 15% probability of mortality in a medical patient admitted for a respiratory condition (outside of COVID-19). The median score of 12 is typical for COVID-19 patients admitted to intensive care units in England, Wales, and Northern Ireland. However, the hospital mortality rate for the 261 patients in this study’s current data with an APACHE II score of 12 is 30.1% (95% CI, 24.0%-36.2%).
SARS-CoV-2 infection was confirmed by respiratory tract polymerase chain reaction test.
Kidney disease was determined from the most recent serum creatinine level prior to this hospital admission, except in patients who were receiving dialysis. Abnormal kidney function was defined as a creatinine level of 130 μmol/L (1.5 mg/dL) or greater for men or 100 μmol/L (1.1 mg/dL) or greater for women not previously receiving dialysis. Cardiovascular disease was defined as New York Heart Association class IV symptoms. Immunosuppression was defined by receipt of recent chemotherapy, radiation, high-dose or long-term steroid treatment, or presence of immunosuppressive disease.
Laboratory results were available when captured for clinical care.
Given variability in clinical assays, relative D-dimer is reported, calculated as the ratio of the measured D-dimer to the local site’s upper limit of normal.