A pair of new studies detail the role of aspirin in the treatment of COVID-19, one estimating lower rates of in-hospital death and pulmonary embolism in moderately ill patients, and the other showing that blood thinners didn't decrease the need for organ support in critically ill patients.
Most beneficial for older, chronically ill patients
Today in JAMA Network Open, a team led by George Washington University researchers published the results of an observational study on the outcomes of 112,269 COVID-19 patients hospitalized with moderate COVID-19 at 64 US health systems participating in the National Institute of Health's National COVID Cohort Collaborative.
Patients were enrolled from Jan 1, 2020, to Sep 10, 2021. Median patient age was 63 years, 52.7% were White, 22.4% were of unknown race, 16.1% were Black, 3.8% were Asian, and 5.0% were of other races.
Before their final analysis, the scientists factored in the fact that aspirin recipients had higher rates of chronic kidney disease (39.4% vs 17.3%), chronic obstructive pulmonary disease (17.6% vs 10.3%), heart disease (55.3% vs 21.1%), high blood pressure (75.6% vs 43.9%), and diabetes (51.1% vs 27.2%). Higher proportions of aspirin recipients also had a history of aspirin use (46.9% vs 4.2%).
Death by 28 days occurred in 10.9% of all patients. The death rate was significantly lower in the 15,272 patients who received aspirin on their first day of hospitalization than in the 96,997 not given aspirin (10.2% vs 11.8%; odds ratio [OR], 0.85).
"The relative mortality reduction of 13.6% and the absolute mortality reduction of 1.6% suggested that 63 patients would need to be treated with early aspirin to prevent 1 in-hospital death," the researchers wrote.
Patients who received aspirin also had significantly lower rates of pulmonary embolism (a blood clot that blocks blood flow in a lung artery; 1.0% vs 1.4%; OR, 0.71) but not deep vein thrombosis (blood clot in a deep vein, usually in a leg). Median aspirin dose was 81 milligrams given for a median of 5 days.
Aspirin appeared most beneficial to patients 61 years and older (OR, 0.79) and those with underlying illnesses (one vs no underlying illness, 6.4% vs 9.2% [OR, 0.68]; two, 10.5% vs 12.8% [OR, 0.80]; three, 13.8% vs 17.0% [OR, 0.78]; more than three, 17.0% vs 21.6% [OR, 0.74]).
Patients in the aspirin group did not have higher rates of gastrointestinal hemorrhage than those in the non-aspirin group (0.8% vs 0.7%; OR, 1.04), nor did they have a higher proportion of cerebral hemorrhage (bleeding in the brain; 0.6% vs 0.4%; OR, 1.32), blood transfusion (2.7% vs 2.3%; OR, 1.14), or the composite of hemorrhagic complications (3.7% vs 3.2%; OR, 1.13).
"Although the composite of hemorrhagic complications was not significantly higher in the early aspirin group, aspirin's risks must be carefully weighed before treatment," the authors wrote. "An RCT [randomized controlled trial] in a diverse patient population with high-risk conditions is needed to confirm our findings, because our study cannot definitively establish causality."
The researchers said the findings are particularly important to countries in which effective COVID-19 vaccines are not widely available. "COVID-19 continues to cause more than 65,000 deaths per week worldwide, highlighting the need for accessible, inexpensive therapies in those who are not vaccinated."
In a George Washington University press release, first author Jonathan Chow, MD, said, "This is our third study and the culmination of 15 months of work looking at aspirin use in hospitalized COVID-19 patients. We continue to find that aspirin use is associated with improved outcomes and lower rates of death in hospitalized patients.
"What’s more, it's low cost and readily available."
Organ support-free days same with, without aspirin
Earlier this week, JAMA published the results of an RCT on the effect of antiplatelet (blood-thinning) medications such as aspirin on survival and organ support-free days in critically ill adult COVID-19 patients.
The ongoing adaptive platform trial testing multiple therapeutic interventions involved 1,557 COVID patients randomly assigned to a blood-thinning therapy (either aspirin [565 patients] or a P2Y12 inhibitor [455]) or no antiplatelet therapy (529) for up to 14 days.
Patients, all of whom were also given preventive anticoagulants, were enrolled from 105 sites in eight countries from Oct 30, 2020, to Jun 23, 2021, and followed for up to 90 days. Enrollment was stopped early on Jun 24, 2021, after the criterion for futility was met. Median patient age was 57 years, and 33.6% were women.
Antiplatelet treatment resulted in a 95.7% posterior probability of futility in terms of more organ support–free days within 21 days. The median for organ support-free days was 7 days in both groups (OR, 1.02).
Among the antiplatelet group, 723 of 1,011 (71.5%) survived to hospital release, compared with 354 of 521 (67.9%) in the control group (median-adjusted OR, 1.27; adjusted absolute difference, 5%; 97% posterior probability of effectiveness). Of survivors, the median for organ support–free days was 14 days in both groups.
Serious adverse events were reported in 5 of 565 (0.9%) patients in the aspirin group, 4 of 455 (0.9%) in the P2Y12 inhibitor group, and 3 of 529 (0.6%) in the control group. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97; adjusted absolute risk increase, 0.8%; 99.4% probability of harm).
"Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support–free days within 21 days," the researchers concluded.
In a related editorial, Jean Connors, MD, and Paul Ridker, MD, MPH, both of Brigham and Women's Hospital, said that all hospitalized COVID-19 patients at low risk for bleeding should receive, at minimum, preventive-dose heparin to prevent thromboinflammation (inflammation combined with blood clots).
And while therapeutic-dose heparin can be considered in some cases, they said, "There is no proven efficacy supporting the addition of traditional antiplatelet therapies to prevent progressive thromboinflammatory complications of COVID-19."
The clinical goal, Connors and Ridker wrote, "should be to avoid thromboinflammation and hospitalization in the first place, an objective largely achievable through aggressive vaccination."
