Questions surrounding the efficacy and safety of escalated thromboprophylaxis regimens in critically ill COVID-19 patients may have been answered as another large trial shows the strategy does not have an advantage over standard care in reducing deaths or venous or arterial thrombosis.
COVID-19 expert guidance supporting the use of intermediate-dose prophylactic anticoagulation early on in the pandemic was fuelled by concerns about the increased risk of thrombotic events observed in patients with COVID-19.
Now, according to early results from the multicentre, randomised INSPIRATION trial published this week, researchers from Iran and the US report on the clinical trial of intermediate-dose vs standard-dose heparin-based thromboprophylaxis among 562 critically ill patients with COVID-19.
The primary efficacy outcome in INSPIRATION, a composite of adjudicated acute venous thromboembolism (VTE), arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality within 30 days, occurred in 45.7% of the intermediate-dose group and 44.1% of the standard-dose group (P = 0.70).
Death occurred in 43.1% of patients vs 40.9% of patients, VTE occurred in 3.3% of patients vs 3.5% of patients, and major bleeding occurred in 2.5% of patients vs 1.4% of patients.
Meanwhile severe thrombocytopenia, defined as a platelet count less than 20 ×103/µL, occurred in six patients in the intermediate-dose group vs 0 patients in the standard-dose group. In addition, there was no benefit of intermediate-dose thromboprophylaxis in any of the prespecified subgroups.
Writing in a linked editorial Dr Hanny Al-Samkari from the Division of Haematology at Massachusetts General Hospital in Boston said the findings challenged many current expert guidance statements but notes that the study had a low rate of thrombotic events overall “raising the possibility of a significant number of uncaptured events.”
According to Dr Al-Samkari, while critically ill patients have been the focus of prophylactic dose escalation, patients with COVID-19 who are moderately ill and not in the ICU might actually be the ones most likely to benefit from the strategy.
“Substantial organ damage has already occurred by the time organ support is required, and therefore heparin-based anticoagulation during an earlier phase of the disease could mitigate microthrombotic and macrothrombotic complications before they occur or potentially exert a meaningful protective anti-inflammatory effect,” he wrote.