Table 3.
Antiplatelet Treatment Studies in Patients with COVID-19
| Type of study | Population | Results | |
|---|---|---|---|
| Observational studies | |||
|
TARGET-COVID, Sub-analysis (185) |
Observational study |
120 hospitalized COVID-19 patients and patients without COVID-19 29% of patients were on aspirin (81–325 mg/day) |
U11-dh TxB2 was lower in aspirin-treated patients (p = 0.003) Inadequate therapeutic aspirin response observed in 91% of patients on 81 mg and 50% of patients on ≥ 162 mg daily aspirin |
| CRUSH COVID registry (186) | Retrospective, observational cohort study | 314 hospitalized COVID-19 patients received aspirin within 24 h of admission; 98 no aspirin | Aspirin use associated with less mechanical ventilation (35.7% versus 48.4%, P = 0.03) and ICU admission (38.8% versus 51.0%, P = 0.04), but no crude association with in-hospital mortality (26.5% versus 23.2%, P = 0.51) |
| Veteran’s health administration study (187) | Retrospective, propensity score matching study | Hospitalized patients COVID-19 13,114 on prior aspirin and 13,114 no aspirin | Preexisting aspirin prescription was associated significant decrease in overall mortality at 14-days (OR = 0.38) and at 30-days (OR = 0.38) |
| Meizlish et al. (188) | Retrospective, propensity score matching study | 638 hospitalized COVID-19 patients treated with aspirin |
In‐hospital aspirin associated with a significantly lower in‐hospital death (HR = 0.52) |
| Merzon et al. (189) | Retrospective population‐based cross‐sectional study | 73 COVID-19 positive patients who were on aspirin and 1548 not on aspirin | Patients on aspirin had a lower rate of COVID-19 (OR, 0.71; p = 0.04), and a shorter clinical duration of COVID-19 (19.8 ± 7.8 vs. 21.9 ± 7.9 days, p = 0.045) |
| Chow JH et al. (190) | Retrospective, propensity score matching study | 6,781 COVID-19 patients on prehospital antiplatelet therapy and 10,566 patients on non‐antiplatelet therapy | Prehospital antiplatelet therapy was associated with significantly lower in‐hospital mortality (HR = 0.81, p < 0.005) |
| National Institutes of Health’s National COVID Cohort Collaborative Data Enclave study (191) | Observational cohort study | 13,795 patients were on early hospital aspirin use and 98,275 not on aspirin | Aspirin use was associated with lower 28-day in-hospital mortality (OR = 0.85; P < 0.001) and pulmonary embolism (OR = 0.71, p = 0.004), similar gastrointestinal hemorrhage, cerebral hemorrhage or blood transfusion |
| Meta-analysis of observational studies (192) | 23 pooled observational studies | 87,824 patients | Antiplatelet therapy was associated with lower risk of mortality (OR = 0.72) |
| Randomized clinical trials | |||
| RECOVERY Trial (NCT04381936) (193) | Randomized clinical trial | 7351 patients received 150 mg/day aspirin and 7541 patients to receive usual care alone |
No difference in 28-day mortality Aspirin therapy was associated with slightly shorter duration of hospitalization (median 8 days, vs 9 days,) a higher discharged from hospital alive within 28 days (75% vs 74%; rate ratio 1·06, p = 0·0062), lower rate of thrombotic events (absolute reduction = 0.6%) and higher major bleeding (absolute increase = 0.6%) |
|
ACTIV-4A trial (194) |
Open label, Bayesian, adaptive randomized clinical trial | 293 non-critically ill patients treated with therapeutic dose of heparin plus a P2Y12 inhibitor vs. 269 patients on therapeutic dose of heparin only (usual care) for 14 days or until hospital discharge | Similar median number of organ support-free days -21 days (adjusted OR = 0.83) and non-significantly higher major bleeding in P2Y12 inhibitor group (adjusted OR = 3.31, P = 0.15) |
|
ACTIV-4B trial (195) |
Adaptive, randomized, double-blind, placebo-controlled trial | 164 symptomatic clinically stable outpatients treated with 81 mg aspirin, 165 patients with 2.5 mg twice daily apixaban, 164 patients with 5 mg twice apixaban twice daily and 164 with placebo | Aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The study was terminated after enrollment of 9% of participants due to lower than anticipated event rate |
|
REMAP-CAP (NCT02735707) (196) |
Ongoing adaptive platform trial testing multiple interventions | 565 critically ill patients received open-label aspirin, 455 received a P2Y12 receptor blocker, or 529 received no antiplatelet therapy for a maximum of 14 days in addition to anticoagulation thromboprophylaxis | There was similar median organ support–free days (7 in both the antiplatelet and control groups), median organ support-free days (14 days) and slightly higher proportions of patients surviving to hospital discharge (median-adjusted OR = 1.27; 96% posterior probability of efficacy), but higher major bleeding with antiplatelet therapy vs. control group (adjusted OR = 2.97, 99.4% probability of harm) |
| Meta-analysis of observational studies (192) | 4 RCTs | – | Conflicting results. No benefit of adding antiplatelet therapy to the standard care, regardless of the baseline illness severity and concomitant anticoagulation intensity |
COVID-19 Coronavirus disease, U11-dh TxB2 urinary 11-dehydro thromboxane B2, OR Odds ratio, RCT randomized control trial