Therapeutic-dose anticoagulation reduces mortality risk compared with prophylactic-dose anticoagulation in patients hospitalized for COVID-19

1. In this meta-analysis of randomized trials involving patients hospitalized with COVID-19, therapeutic-dose anticoagulation was found to be associated with a lower 28-day mortality risk compared with prophylactic-dose anticoagulation.

2. In studies that utilized intermediate dosing, mortality risk appeared higher for therapeutic-dose versus intermediate-dose anticoagulation, and similar between prophylactic-dose and intermediate-dose anticoagulation.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Various anticoagulants have been assessed for effectiveness against thrombosis in patients hospitalized for COVID-19, but optimal drug selection and dosing remain unclear, particularly among patients with differing disease severity. This study aimed to synthesize the data from existing randomized trials to elucidate associations between anticoagulant dose and clinical outcomes. Data were collected from twenty-two studies across twenty-one countries. Overall, patients receiving therapeutic-dose anticoagulation were found to have a lower absolute 28-day mortality risk compared to those receiving prophylactic-dose anticoagulation. Therapeutic-dose anticoagulation was also associated with a higher absolute mortality risk versus intermediate-dose anticoagulation, and intermediate-dose anticoagulation was associated with little change in absolute mortality risk when compared with prophylactic-dose anticoagulation. Higher doses of anticoagulation were linked to fewer thromboembolic events but more major bleeding events. Degree of respiratory support did not seem to affect the associations between anticoagulation and these clinical outcomes. The generalizability of this study was limited by its lack of data on direct oral anticoagulants, its use of major bleeding as the only primary adverse event, and relatively few comparisons of intermediate dosing. Nevertheless, this study provided an understanding of the relationships between anticoagulant dose and short-term mortality in patients hospitalized with COVID-19.

Click to read the study in AIM

Relevant Reading: Thromboprophylaxis in Patients with COVID-19: Systematic Review of National and International Clinical Guidance Reports

In-Depth [systematic review and meta-analysis]: This meta-analysis aimed to characterize the associations between anticoagulant dose and various clinical outcomes among patients with COVID-19. Trials were eligible for inclusion if they randomly assigned higher-dose and lower-dose anticoagulants among hospitalized patients; anticoagulant regimens were sorted into therapeutic-dose, prophylactic-dose, and intermediate-dose. The primary outcome was all-cause mortality within 28 days following randomization; secondary outcomes included progression to invasive mechanical ventilation (IMV) or death, arterial or venous thromboembolic events, and major bleeding. Only one trial evaluated direct oral anticoagulants. Mortality data for 6297 patients receiving therapeutic- versus prophylactic-dose anticoagulation were obtained from 11 trials, yielding a summary odds ratio (OR) of 0.77 (95% CI, 0.64 to 0.93) and an absolute mortality risk of 8% for therapeutic-dose anticoagulation compared with an assumed risk of 10% for prophylactic-dose anticoagulation. There were a total of 222 thromboembolic events (summary OR, 0.48 [95% CI, 0.36 to 0.64]) and 81 major bleeding events (summary OR, 1.90 [95% CI, 1.19 to 3.05]) in this population. Mortality data for 1798 patients receiving therapeutic- versus intermediate-dose anticoagulation were obtained from 6 trials, yielding a summary OR of 1.21 (95% CI, 0.93 to 1.58) and an absolute mortality risk of 27% for therapeutic-dose anticoagulation compared with an assumed risk of 24% for intermediate-dose anticoagulation. There were a total of 121 thromboembolic events (summary OR, 0.63 [95% CI, 0.43 to 0.93]) and 46 major bleeding events (summary OR, 1.21 [95% CI, 0.66 to 2.20]) in this population. Mortality data for 3897 patients receiving intermediate- versus prophylactic-dose anticoagulation were obtained from 10 trials, which yielded a summary OR of 0.95 (95% CI, 0.76 to 1.19). There were 121 thromboembolic events (summary OR, 0.67 [95% CI, 0.45 to 1.00]) and 44 major bleeding events (summary OR, 1.22 [95% CI, 0.66 to 2.25]) in this population. Overall, this study showed potential associations between the dose of anticoagulants and mortality, thromboembolic events, and major bleeding events in patients hospitalized for COVID-19.

Image: PD

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