Studies yield new insights into anticoagulant use and COVID-19 outcomes
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Two studies presented at the virtual ASH Annual Meeting and Exposition yielded conflicting results in terms of the effect of anticoagulants on COVID-19 outcomes.
According to an author of one of the studies, a wide range of well-conducted research is crucial to advancing knowledge of COVID-19, regardless of a study’s outcome.
“Given this is a pandemic, our clinical treatment practices have been evolving as we understand more about SARS-CoV-2 infection and have more data,” Gwendolyn Ho, MD, MAS, a hematologist/oncologist at Kaiser Permanente Medical Center in Sacramento, California, said in an interview with Healio. “We really need good prospective studies looking at whether to use and/or how to use anticoagulants/antiplatelets in patients with COVID-19 to better affect the severity of disease and, hopefully, reduce the morbidity and mortality in these patients.”
Effect of dose on survival
In one study, Filip Ionescu, MD, an internal medicine specialist at William Beaumont Hospital in Royal Oak, Michigan, and colleagues evaluated 3,480 consecutive patients with COVID-19 (mean age, 64.5 ±17 years; 51.5% women; 52.1% Black) admitted between March 13 and May 5 to one of eight hospitals within a large academic hospital system in Michigan. The researchers stratified patients based on whether they received no anticoagulation (10.4%; n = 361); prophylactic anticoagulation for most of their hospitalization (60.9%; n = 2,121) or at least 3 days of therapeutic anticoagulation (28.7%; n = 998).
A propensity score-weighted Kaplan-Meier plot showed a significant difference in 25-day survival probability among patients receiving therapeutic vs. prophylactic anticoagulation (57.5% vs. 50.7%; P < .001). In addition, a propensity score-weighted multivariate proportional hazards model adjusted for age, BMI and ICU status showed a lower mortality risk with both prophylactic (HR= 0.35; 95% CI, 0.22-0.54) and therapeutic (HR = 0.14; 95% CI, 0.05-0.23) anticoagulation vs. no anticoagulation.
Patients who received therapeutic anticoagulation had a greater incidence of major bleeding (8.1%) than those who had prophylactic anticoagulation (2.2%) or no anticoagulation (5.5%).
“We postulated that anticoagulation could be beneficial based on bedside observation of hypercoagulation and data from laboratory animals that it interferes with inflammatory pathways,” Ionescu said in an interview with Healio. “Now we recognize that the most severe form of COVID-19 is actually a hyperinflammatory state. We see that the patients who benefit most from anticoagulation are those with evidence of severe pulmonary inflammation.”
Risk for severe outcomes
In their retrospective cohort study, Ho and colleagues evaluated 28,076 adults who tested positive for COVID-19 between Feb. 25 and May 8 within the Kaiser Permanente Northern California health system. They stratified patients based on electronic medical records documenting a filled prescription or active treatment with antiplatelets or anticoagulants within 90 days before COVID-19 diagnosis.
“There is a SARS-CoV-2-associated coagulopathy that is thought to contribute to the morbidity and mortality associated with infection,” Ho said. “There has been increased interest and clinical use of anticoagulation and antiplatelet therapy to try to address this, but there are not much data on whether it actually influences outcomes. We wanted to see if those patients who were on chronic anticoagulants and antiplatelets had differences in the severity of COVID-19 infection compared with those not on these medications.”
Among the patients, 6% (n = 167) used antiplatelets, 2% (n = 69) used anticoagulants and 0.2% (n = 7) used both.
ED visit, inpatient hospitalization, ICU stay, venous thromboembolism or mortality between COVID-19 diagnosis and June 9 (or 45 days after COVID-19 diagnosis) served as the study’s primary outcomes. Researchers defined severe outcome as inpatient hospitalization, mechanical ventilation or mortality. They used logistic regression to calculate ORs and 95% CIs for the correlation between anticoagulants/antiplatelets and primary outcomes.
The researchers found that, after adjusting for sociodemographic and clinical characteristics, chronic use of anticoagulants or antiplatelets did not appear to be associated with a reduced risk for any of the primary outcomes (OR = 1.03; 95% CI, 0.74-1.45).
“We did see an association, however, with decreased odds of ventilator use among those on these drugs compared with those not on these drugs,” Ho said.
Older patients demonstrated an elevated risk for all outcomes expect for VTE, and those aged 80 years and older had the highest risk compared with those aged 18 to 29 years (OR = 13.62; 95% CI, 7.69-24.11). Men had increased risk for unfavorable outcomes, as did Asian and Hispanic patients compared with white patients. Researchers also observed a higher risk for mortality among patients with underlying obesity (OR = 2.28; 95% CI, 1.31-3.95) and hypertension (OR = 2.03; 95% CI, 1.3-3.19), but not among those who had diabetes (OR = 1.43; 95% CI, 0.89-2.28).
‘Important information’
Ionescu said differences in the patient populations and the medications evaluated may have been responsible for the contradictory outcomes of the studies. He noted that Ho’s study included both hospitalized individuals and outpatients with COVID-19, as well as use of both anticoagulants and antiplatelets.
“If anything, I would say the two studies are complementary,” he said. “They looked at patients with milder disease, and this is what we’ve seen, as well — that anticoagulation doesn’t have the same benefit in patients with mild disease. They just don’t have the same level of inflammation as the patients who require ICU-level of care.”
Ho said that each study is distinct and valuable.
“The major difference in these two studies is that we looked primarily at all patients with COVID-19 diagnosis, including those in the outpatient and inpatient settings, and we looked at how severe their disease was based on need for hospitalization,” Ho said. “The other abstract looked only at patients hospitalized with COVID-19 — therefore, patients with greater severity of disease — and how varying doses of anticoagulation may influence outcomes in these patients. Both studies give us important information.”
Given the pressing need to understand COVID-19, quality research into this topic is essential, Ho said.
“These are unprecedented times,” she said. “The more well-done studies and helpful information we have, the better equipped we will be to combat this pandemic.”
References:
Ho G, et al. Abstract 206. Presented at: ASH Annual Meeting and Exposition (virtual meeting). Dec 5-8, 2020.
Ionescu F, et al. Abstract 577. Presented at: ASH Annual Meeting and Exposition (virtual meeting). Dec 5-8, 2020.
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Ionescu F, et al. Abstract 577. Presented at: ASH Annual Meeting and Exposition (virtual meeting). Dec 5-8, 2020.
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