No Support for Aspirin Treatment in Hospitalized COVID Patients
NEW YORK (Reuters Health) – Results of a large randomized controlled trial do not support adding daily aspirin to standard thromboprophylaxis or therapeutic anticoagulation in patients hospitalized with COVID-19.
In the RECOVERY study, treatment with 150 mg aspirin daily on top of usual care did not reduce the death rate at 28 days or the likelihood of progressing to invasive mechanical ventilation but was associated with a small increase in the rate of being discharged alive within 28 days.
The results were “consistent across the prespecified subgroups of age, sex, ethnicity, duration of symptoms before randomization, amount of respiratory support at randomization, and use of corticosteroids,” report Dr. Peter Horby of the University of Oxford, in the U.K., and the RECOVERY Collaborative Group in The Lancet.
“As expected, allocation to aspirin was associated with an increased risk of major bleeding and a decreased risk of thromboembolic complications, such that for every 1000 patients treated with aspirin, approximately six more patients would have a major bleeding event and approximately six fewer patients would have a thromboembolic event,” they say.
The findings are based on 7,351 COVID-19 patients randomized to usual standard of care plus 150 mg aspirin once per day until discharge and 7,541 like COVID-19 patients randomized to usual standard of care alone (control group). The trial took place at 177 hospitals in the U.K., two in Indonesia, and two in Nepal.
Overall, 1,222 (17%) patients in the aspirin group and 1,299 (17%) in the control group died within 28 days (rate ratio, 0.96; 95% confidence interval, 0.89 to 1.04).
Patients taking aspirin had a slightly shorter length of hospital stay (median, eight days vs. nine days) and a higher proportion of patients were discharged from hospital alive within 28 days (75% vs. 74%; rate ratio, 1.06; 95% CI, 1.02 to 1.10).
Among patients not on invasive mechanical ventilation at the outset, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio, 0.96; 95% CI, 0.90 to 1.03).
Aspirin use was associated with a reduction in thrombotic events (4.6% vs. 5.3%) and an increase in major bleeding events (1.6% vs. 1.0%).
The authors of a linked comment note that the “coagulopathy caused by SARS-CoV-2 seen in patients hospitalized with COVID-19, especially those with severe or critical illness, is by now well established. For the most part, randomized trials to date have not shown benefits of add-on or escalated antithrombotic therapy over usual standard of care.”
Dr. Alex Spyropoulos of Lenox Hill Hospital in New York and Dr. Marc Bonaca of University of Colorado in Aurora wonder: “Have we set too high a bar in the design of antithrombotic clinical trials in COVID-19? Traditional antithrombotic clinical trial designs in patients who are hospitalized used a composite of thromboembolic disease and mortality as primary endpoints in enriched populations, and it was the rare trial that gave us reductions in mortality alone if thrombotic causes were the dominant driver,” they point out.
“Whether antithrombotics reduce thrombotic microangiopathy is still a matter of debate. And yet, the entire premise of many COVID-19 antithrombotic clinical trial designs, which are based on primary endpoints of mortality or disease severity, is that they would have potential to reduce thrombotic microangiopathy and ameliorate the course of disease on the basis of thromboinflammatory mechanisms. It can indeed be a slippery slope to base an entire clinical trial design on an unproven hypothesis,” they write.
“Although it can be argued that the urgency of the pandemic required broader outcomes to speed up discovery, perhaps the time has come for us to rethink how we study the coagulopathy of COVID-19, returning to principles that led to traditional antithrombotic clinical trial designs,” they conclude.
Funding for the study was provided by UK Research and Innovation (Medical Research Council), National Institute of Health Research, and the Wellcome Trust through the COVID-19 Therapeutics Accelerator.
SOURCE: https://bit.ly/32ysmeN and https://bit.ly/3xn7CSw The Lancet, online November 17, 2021.
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