Results from the international RAPID trial support the use of therapeutic heparin in moderately ill COVID-19 patients in hospital who have increased D-dimer levels, say researchers.

The year-long trial trial in patients at 28 hospitals across six countries found that therapeutic heparin reduced the odds of death at 28 days compared with prophylactic heparin without increasing the risk of major bleeding which was low across the study.

There was not a signification difference between the two anticoagulation approaches the combined primary outcome of death, ventilation or admission to intensive care, the researchers reported in the BMJ.

But they concluded that the ‘substantially decreased odds of all cause death’ and low risk of major bleeding, suggests that ‘therapeutic heparin in beneficial in moderately ill patients with COVID-19’.

The analysis included 465 adults admitted to hospital and had increased D-dimer levels in the first five days of admission but not requiring ventilation and being managed on a ward. The mean age was 60 years, 56.8% were men and the mean body mass index was 30kg/m2.

I love the ⁦@bmj_latest⁩ visual abstracts!
This one summarises the elegant RAPID trial led by ⁦@sholzberg⁩, which adds to the accumulating data that full-dose heparin improves outcome in moderate COVID-19 when compared to prophylactic heparin pic.twitter.com/hQgsk3X5mB

— Professor Beverley Hunt (@bhwords) October 14, 2021

At 28 days, the primary outcome of death, mechanical or non-invasive ventilation or admittance to ICU had happened in 16.2% given therapeutic heparin and 21.9% in the prophylactic heparin group.

Looking at deaths specifically, there were 18 patients (7.6%) on prophylactic heparin and four patients (1.8%) on therapeutic – a reduction of 78%.

The team also found venous thromboembolism in two patients (0.9%) in the therapeutic heparin arm and six (2.5%) taking prophylactic heparin.

Major bleeding was reported in two patients (0.9%) on therapeutic heparin and four (1.7%) taking prophylactic heparin.

While there were differences between the groups for ventilation and ICU admission, these were smaller and not significant, the analysis showed.

The researchers noted that the reduction in mortality seen in RAPID was more pronounced that than reported in the ATTACC, ACTIV-4a and REMAP-CAP studies.

This could be down to chance but could also relate to a bigger contrast between treatment groups with others using variable or intermediate doses. The type of anticoagulation used may also have an impact, they said.

‘Randomised trials suggest that therapeutic heparin is beneficial in moderately ill patients with COVID-19 admitted to hospital, but of no benefit and potential harm when provided to critically ill patient. Given the disparate findings in these two patient populations, there is hesitancy to adopt therapeutic heparin as standard care in moderately ill patients with COVID-19,’ they concluded.

‘Although the difference in the primary outcome was not statistically significant, a noticeable reduction in mortality and low risk of bleeding was observed with therapeutic heparin,’ they added.

Pointing to the ‘elegant’ results on social media, Professor Beverley Hunt, medical director of Thrombosis UK said it added ‘to the accumulating data that full-dose heparin improves outcome in moderate COVID-19 when compared to prophylactic heparin’.