Author : Fred Fuentes, MD
The National Institutes of Health (NIH) of the United States releases two updates on the ongoing multi-plaform randomized controlled trial on anticoagulation in Covid-19. The trial is a huge collaboration among three different RCTs spanning four continents, over 300 hospitals, with more than 12,000 participants, aiming to determine whether full-dose (therapeutic) anticoagulation is beneficial in moderately ill to critically ill patients with Covid-19 compared to lower (prophylactic) dose.
Based on recommendations by their monitoring boards composed of experts, enrollment was halted in the subgroup of critically-ill patients because therapeutic dose “did not reduce the need for organ support” and “a potential for harm could not be excluded”. This news came as a surprise to those who advocated higher doses of anticoagulants for ICU patients based on Covid-19’s well-known association with thrombosis. It is possible, as with the other therapies for Covid-19, that anticoagulants may also be phase-specific, depending on the stage the patient is in. Any incremental benefit of full dose in ICU patients may be offset by bleeding complications.
However, in another press release a month later, the NIH announced “improved outcomes” with full-dose anticoagulation in moderately ill (hospitalized) Covid-19 patients, compared to lower doses. In particular, it “reduced the requirement of vital organ support such as the need for ventilation” and there was “a trend in possible reduction of mortality” but is still being further analyzed. Nevertheless, the full results of the study are still being worked on and no definitive date of release has yet been announced.
Still, several questions remain such as what to do with moderately ill patients started on full-dose anticoagulation and subsequently needing intensive care, as well as duration of prophylaxis post-discharge among others.
Our existing PSVM interim guideline on anticoagulation in Covid-19 does recommend an intermediate-dose of anticoagulation in severe to critically ill patients, but reserve full doses in those with established indications such as presence of deep vein thrombosis or pulmonary embolism. Several trials on intermediate dose are ongoing (e.g. INSPIRATION, COVI-DOSE, X-COVID 19) to further inform us whether this dose improves outcomes where full-dose has failed. As for moderately ill patients, the PSVM guideline still recommends prophylactic dose anticoagulation but may yet be revised as more data and full results become available. Stay tuned.
First update here:
NIH ACTIV Trial of blood thinners pauses enrollment of critically ill COVID-19 patients <https://www.nih.gov/news-events/news-releases/nih-activ-trial-blood-thinners-pauses-enrollment-critically-ill-covid-19-patients> Up
NIH ACTIV Trial of blood thinners pauses enrollment of critically ill COVID-19 patients Anticoagulation drugs did not reduce the need for organ support.
Second update here:
Full-dose blood thinners decreased need for life support and improved outcome in hospitalized COVID-19 patients <https://www.nih.gov/news-events/news-releases/full-dose-blood-thinners-decreased-need-life-support-improved-outcome-hospitalized-covid-19-patients>
Full-dose blood thinners decreased need for life support and improved outcome in hospitalized COVID-19 patients Full doses of blood thinners, in addition to being safe, were superior to the doses normally given to prevent blood clots in hospitalized patients.