Abstract
Background: Reported results of clinical trials assessing higher-dose anticoagulation in patients hospitalized for COVID-19 have been inconsistent.
Purpose: To estimate the association of higher- versus lower-dose anticoagulation with clinical outcomes.
Data Sources: Randomized trials were identified from the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov with no restriction by trial status or language.
Study Selection: Eligible randomized trials assigned patients hospitalized for COVID-19 to higher- versus lower-dose anticoagulation.
Data Extraction: 20 eligible trials provided data in a prospectively agreed format. Two further studies were included based on published data. The primary outcome was all-cause mortality 28 days after randomization. Secondary outcomes were progression to invasive mechanical ventilation or death, thromboembolic events, and major bleeding.
Data Synthesis: Therapeutic- compared with prophylactic-dose anticoagulation with heparins reduced 28-day mortality (OR, 0.77 [95% CI, 0.64 to 0.93]; I 2 = 29%; 11 trials, 6297 patients, of whom 5456 required low or no oxygen at randomization). The ORs for 28-day mortality were 1.21 (CI, 0.93 to 1.58; I 2 = 0%) for therapeutic-dose compared with intermediate-dose anticoagulation (6 trials, 1803 patients, 843 receiving noninvasive ventilation at randomization) and 0.95 (CI, 0.76 to 1.19; I 2 = 0%; 10 trials, 3897 patients, 2935 receiving no or low oxygen at randomization) for intermediate- versus prophylactic-dose anticoagulation. Treatment effects appeared broadly consistent across predefined patient subgroups, although some analyses were limited in power. Higher- compared with lower-dose anticoagulation was associated with fewer thromboembolic events, but a greater risk for major bleeding.
Conclusion: Therapeutic-dose compared with prophylactic-dose anticoagulation reduced 28-day mortality. Mortality was similar for intermediate-dose compared with prophylactic-dose anticoagulation and higher for therapeutic-dose compared with intermediate-dose anticoagulation, although this comparison was not estimated precisely.
Purpose: To estimate the association of higher- versus lower-dose anticoagulation with clinical outcomes.
Data Sources: Randomized trials were identified from the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov with no restriction by trial status or language.
Study Selection: Eligible randomized trials assigned patients hospitalized for COVID-19 to higher- versus lower-dose anticoagulation.
Data Extraction: 20 eligible trials provided data in a prospectively agreed format. Two further studies were included based on published data. The primary outcome was all-cause mortality 28 days after randomization. Secondary outcomes were progression to invasive mechanical ventilation or death, thromboembolic events, and major bleeding.
Data Synthesis: Therapeutic- compared with prophylactic-dose anticoagulation with heparins reduced 28-day mortality (OR, 0.77 [95% CI, 0.64 to 0.93]; I 2 = 29%; 11 trials, 6297 patients, of whom 5456 required low or no oxygen at randomization). The ORs for 28-day mortality were 1.21 (CI, 0.93 to 1.58; I 2 = 0%) for therapeutic-dose compared with intermediate-dose anticoagulation (6 trials, 1803 patients, 843 receiving noninvasive ventilation at randomization) and 0.95 (CI, 0.76 to 1.19; I 2 = 0%; 10 trials, 3897 patients, 2935 receiving no or low oxygen at randomization) for intermediate- versus prophylactic-dose anticoagulation. Treatment effects appeared broadly consistent across predefined patient subgroups, although some analyses were limited in power. Higher- compared with lower-dose anticoagulation was associated with fewer thromboembolic events, but a greater risk for major bleeding.
Conclusion: Therapeutic-dose compared with prophylactic-dose anticoagulation reduced 28-day mortality. Mortality was similar for intermediate-dose compared with prophylactic-dose anticoagulation and higher for therapeutic-dose compared with intermediate-dose anticoagulation, although this comparison was not estimated precisely.
| Original language | English |
|---|---|
| Pages (from-to) | 59-69 |
| Number of pages | 11 |
| Journal | Annals of Internal Medicine |
| Volume | 178 |
| Issue number | 1 |
| Early online date | 24 Dec 2024 |
| DOIs | |
| Publication status | Published - Jan 2025 |
Bibliographical note
Publisher Copyright:© 2025 American College of Physicians. All rights reserved.
Funding
The WHO contributed to the design and conduct of the study by convening the WHO COVID-19 Clinical Management and Characterization Working Group. This group assembled information on ongoing trials and invited trial investigators to participate in this prospective meta-analysis. The WHO chief scientist invited trial investigators to participate and provided a secure portal for submission of data. Funding for administrative and communications support was provided by the World Health Organization.
| Funders |
|---|
| World Health Organization |
Keywords
- Anticoagulants
- Cardiology and cardiovascular diseases
- Clinical trials
- COVID-19
- Hemorrhage
- Hospital medicine
- Mortality
- Prophylaxis
- Randomized trials
- Vascular medicine
