Current best evidence for clinical care (more info)
BACKGROUND: Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown.
METHODS: This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding.
RESULTS: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24).
CONCLUSION: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.
| Discipline / Specialty Area | Score |
|---|---|
| Respirology/Pulmonology | |
| Hemostasis and Thrombosis | |
| Infectious Disease | |
| Intensivist/Critical Care | |
| Hospital Doctor/Hospitalists | |
| Internal Medicine | |
Extends the results of INSPIRATION out to 90 days, confirming a lack of benefit for intermediate-dose AC compared with prophylactic-dose AC for critically ill patients with COVID.
This is a preliminary study with a number of limitations. Although this may be supportive of an evidence-based change in clinical approach on the wards as other investigations accumulate, it is not particularly important in isolation.
Previous studies have suggested that using higher-dose anticoagulation is not beneficial in patients admitted to the ICU with COVID.
This multicenter international trial shows that intermediate-dose anticoagulation with enoxaparin in ICU patients with COVID-9 has no benefit when compared with standard-dose enoxaparin.
This article gives me more confidence that I am not under-treating ICU patients with COVID-19 for prevention of thrombotic events using standard VT prophylaxis. There may also be a safety benefit to avoiding intermediate anticoagulation in the long run.