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Intermediate and standard-dose prophylactic anticoagulation in COVID-19 equivalent

Although thromboembolic complications are a recognised feature of infection with COVID-19 the optimal anticoagulation regime is unclear.

Early in the COVID-19 pandemic it was noted that infection led to endothelial injury and a prothrombotic milieu with both venous and arterial micro- and macro-thrombosis being a common feature.

In fact, a systematic review in November 2020 revealed how among those hospitalised with COVID-19, the pooled estimate of venous thromboembolism was 17%.

However, while disturbances of the coagulation system are a recognised complication of infection with COVID-19, there is limited evidence to guide the selection of the most effective anticoagulant regime.

This prompted a team from the Cardiovascular Intervention Research Centre, Tehran, Iran, to undertake a randomised, controlled trial, to examine the impact on thrombosis, use of extracorporeal oxygen (ECMO) and mortality from two anticoagulant regimes.

The team recruited patients from 10 centres across the country and considered two separate hypotheses. The first was to compare intermediate dose vs standard dose of anticoagulation and the second was to consider the impact of additional statin therapy although this data was not reported.

The team recruited PCR COVID-19 positive patients admitted to an intensive care unit (ICU). The anticoagulant used was enoxaparin and eligible patients were then randomised on a 1:1 basis to either enoxaparin 1mg/kg daily (intermediate dose) or 40 mg daily (standard dose).

The treatment assignment continued until the 30-day follow-up, irrespective of hospital discharge status.

The primary outcome was a composite of adjudicated acute venous thromboembolism, arterial thrombosis, ECMO or all-cause mortality within 30 days of enrolment.


A total of 562 patients with a median age of 62 years (42.2% women) and a median body mass index of 27 were included in the final analysis.

The median length of hospital stay was six days in both groups and a similar proportion of patients (61.2% vs 60.8%, intermediate vs standard) were discharged from ICU.

The primary outcome occurred in 126 (45.7%) of patients in the intermediate group and 126 (44.1%) of the standard dose, giving an odds ratio of 1.06 (95% CI 0.76–1.48, p =0.70).

Similarly, all-cause mortality occurred in 236 (42%) in the intermediate and 119 (43.1%) in the standard therapy group and again this difference was not significantly different.

The authors concluded that their results do not support the use of empirical intermediate-dose prophylactic anticoagulant therapy compared with standard dosing.

INSPIRATION Investigators. Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomised Clinical Trial. JAMA 2021.