Full-dose anticoagulants reduced need for respiratory support and improved outcomes in non-ICU Covid-19 patients, study finds

Based on a new report released by the National Institutes of Health (NIH), full-dose anticoagulation has been shown to be more beneficial over lower prophylactic doses in reducing the need for critical life-saving measures such as mechanical ventilation in moderately ill, non-ICU patients. patients hospitalized for Covid-19.

“There appears to be a window of time – before ICU admission – in which full-dose anticoagulation is beneficial,” said Amesh Adalja, MD, infectious disease physician and principal investigator at the ‘Johns Hopkins University. “This illustrates the nuanced treatment needed for COVID-19 depending on the severity and phase of the disease.”

During the first months of the pandemic, it was not uncommon for healthcare providers to subject patients to protective or prophylactic doses of anticoagulants (as opposed to a full dose) upon admission to hospital. . Blood thinners such as low molecular weight heparin or unfractionated heparin reduce the risk of blood clots, a common and potentially fatal condition that has become quite evident in the first few months of patients being treated with Covid -19.

High rates of thrombosis or blood clots, triggered by the inflammation of Covid-19, can lead to heart attacks, strokes, and pulmonary emboli (lung clots). Such clinical findings have therefore led to the initiation of various anticoagulation protocols as well as to a need for randomized data concerning the routine administration of high doses of anticoagulation to hospitalized patients with Covid-19.

The NIH report describes the results of three related clinical trials (REMAP-CAP, ACTIV-4, and ATTACC) investigating the safety and efficacy of full-dose anticoagulation for treating both moderately ill adults (not -USI) or critically ill (ICU). hospitalized with COVID-19, compared to a prophylactic or lower dose commonly used to prevent blood clots in hospitalized patients.

But last month, the 3 trials halted the registration of the seriously ill subgroup after data demonstrated that full-dose anticoagulation initiated in ICU was not beneficial and may have caused harm in some patients. It could be inferred that safety was likely a factor in the decision to suspend the recruitment of intensive care patients, taking into account the potential damage (caused by excessive bleeding).

This was not the case, however, for moderately ill patients, defined as those not requiring intensive care (mechanical ventilation or interventions to increase blood pressure). In fact, in this subgroup of almost 1000 patients (which represented 80% of the recruitment in the three trials), it was noted that full doses of low molecular weight heparin or unfractionated heparin were greater than lower prophylactic doses for the primary endpoint of need. for ventilation or other organ support interventions 21 days after randomization.

“As one might suspect, there appears to be a sweet spot when it comes to blood thinners in # Covid-19. Severely ill – no signs of benefit, moderate illness seems to have some benefit. If only we had randomized people in March… ”said Dr. Laura Westafer, emergency physician and research director at the University of Massachusetts Baystate in a tweet earlier today.

It is important to realize that with a large number of patients currently requiring hospitalization over the next few months, the results of these studies may help reduce the potential for intensive care admission, with more aggressive treatment earlier. in the course of the hospital. It goes without saying that with a shortage of not only intensive care beds but skilled staff, these findings can help streamline and improve care in resource-limited areas of the United States.

Beyond that, it also highlights the important role of timing and dose of anticoagulation during Covid-19. Based on these results, the take-home message is that initiation of full-dose anticoagulation is essential and effective earlier in the course of the disease. Patients who were critically ill in the intensive care unit at the time of enrollment did not receive full dose anticoagulation, implying that starting treatment much earlier in their disease course would have been beneficial.

And if earlier treatment leads to better results, the resulting question is whether initiation of anticoagulation in Covid-19 patients who do not require hospitalization may also be of benefit. The ACTIV-4B trial is currently recruiting patients with Covid-19 who do not require hospitalization, randomizing them to the direct oral anticoagulant, apixiban, aspirin or placebo. This is a pivotal trial that could offer new therapy for the outpatient management of patients with Covid-19 who are safe for discharge, potentially preventing progression of the disease requiring hospitalization.