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Full-dose anticoagulation was superior to low, prophylactic doses in reducing the need for vital organ support such as ventilation in moderately ill patients hospitalized for COVID-19, according to a report released today by the National Institutes of Health (NIH).
“This is a major advance for patients hospitalized with COVID. Full dose of anticoagulation in these non-ICU patients improved outcomes and there’s a trend toward a reduction in mortality,” Judith Hochman, MD, director of the Cardiovascular Clinical Research Center at NYU Langone Medical Center in New York City, told theheart.org | Medscape Cardiology.
“We have treatments that are improving outcomes but not as many that reduce mortality, so we’re hopeful when the full dataset comes in that will be confirmed,” she said.
The observation of increased rates of blood clots and inflammation among COVID-19 patients, which can lead to complications such as lung failure, heart attack, and stroke, has given rise to various anticoagulant treatment protocols and a need for randomized data on routinely administering increased doses of anticoagulation to hospitalized patients.
Today’s top-line findings come from three linked clinical trials — REMAP-CAP, ACTIV-4, and ATTACC — examining the safety and efficacy of full-dose anticoagulation to treat moderately ill or critically ill adults hospitalized with COVID compared with a lower dose typically used to prevent blood clots in hospitalized patients.
Last month, all three trials paused enrollment of the critically ill subgroup after results showed that full-dose anticoagulation started in the intensive care unit (ICU) was not beneficial and may have been harmful in some patients.
Moderately ill patients with COVID-19, defined as those who did not require ICU care or organ support, made up 80% of participants at enrollment in the three trials, Hochman said.
Among more than 1000 moderately ill patients reviewed as of the data cut with the data safety monitoring board, full doses of low molecular weight or unfractionated heparin were superior to low prophylactic doses for the primary endpoint of need for ventilation or other organ supportive interventions at 21 days after randomization.
This met the predefined threshold for 99% probability of superiority and recruitment was stopped, Hochman reported. “Obviously safety figured into this decision. The risk/benefit ratio was very clear.”
The results do not pertain to patients with a previous indication for anticoagulation, who were excluded from the trials.
Data from an additional 1000 patients will be reviewed and the data published sometime in the next 2 to 3 months, she said.
With large numbers of COVID-19 patients requiring hospitalization, the outcomes could help reduce the overload on intensive care units around the world, the NIH noted.
The results also highlight the critical role of timing in the course of COVID-19.
“We believe that full anticoagulation is effective early in the disease course,” Hochman said. “Based on the results so far from these three platform trials, those that were very, very sick at the time of enrollment really didn’t benefit and we needed to have caught them at an earlier stage.
“It’s possible that the people in the ICU are just different and the minute they get sick they need the ICU; so we haven’t clearly demonstrated this time course and when to intervene, but that’s the implication of the findings.”
The question of even earlier treatment is being examined in the partner ACTIV-4B trial, which is enrolling patients with COVID illness not requiring hospitalization and randomizing them to the direct oral anticoagulant apixaban or aspirin or placebo.
“It’s a very important trial and we really want to get the message out that patients should volunteer for it,” said Hochman, who is principal investigator of the ACTIV-4 trial.
In the United States, the ACTIV-4 trial is being led by a collaborative effort involving a number of universities, including the University of Pittsburgh in Pennsylvania and New York University in New York City.
The REMAP-CAP, ACTIV-4, and ATTACC study platforms span five continents in more than 300 hospitals and are supported by multiple international funding organizations including the National Institutes of Health, Canadian Institutes of Health Research, the National Institute for Health Research (UK), the National Health and Medical Research Council (Australia), and the PREPARE and RECOVER consortia (European Union).