Treatments Associated with Lower Mortality among Critically Ill COVID-19 Patients: A Retrospective Cohort Study
Zhao et al.
, Treatments Associated with Lower Mortality among Critically Ill COVID-19 Patients: A Retrospective Cohort..
, Anesthesiology, doi:10.1097/ALN.0000000000003999
Retrospective 2,070 hospitalized patients in the USA, showing lower mortality with aspirin treatment.
risk of death, 43.0% lower, HR 0.57, p < 0.001, treatment 121 of 473 (25.6%), control 140 of 473 (29.6%), adjusted per study, PSM.
risk of death, 28.0% lower, HR 0.72, p = 0.03, treatment 473, control 1,597, adjusted per study, multivariable.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Zhao et al., 1 Oct 2021, retrospective, USA, peer-reviewed, 6 authors.
Abstract: Critical Care Medicine
Background: Mortality in critically ill COVID-19 patients remains high.
Although randomized controlled trials must continue to definitively evaluate
treatments, further hypothesis-generating efforts to identify candidate treatments are required. This study’s hypothesis was that certain treatments are
associated with lower COVID-19 mortality.
Methods: This was a 1-yr retrospective cohort study involving all COVID-19
patients admitted to intensive care units in six hospitals affiliated with Yale
New Haven Health System from February 13, 2020, to March 4, 2021. The
exposures were any COVID-19–related pharmacologic and organ support
treatments. The outcome was in-hospital mortality.
Results: This study analyzed 2,070 patients after excluding 23 patients
who died within 24 h after intensive care unit admission and 3 patients who
remained hospitalized on the last day of data censoring. The in-hospital mortality was 29% (593 of 2,070). Of 23 treatments analyzed, apixaban (hazard
ratio, 0.42; 95% CI, 0.363 to 0.48; corrected CI, 0.336 to 0.52) and aspirin (hazard ratio, 0.72; 95% CI, 0.60 to 0.87; corrected CI, 0.54 to 0.96)
were associated with lower mortality based on the multivariable analysis with
multiple testing correction. Propensity score–matching analysis showed an
association between apixaban treatment and lower mortality (with vs. without
apixaban, 27% [96 of 360] vs. 37% [133 of 360]; hazard ratio, 0.48; 95%
CI, 0.337 to 0.69) and an association between aspirin treatment and lower
mortality (with vs. without aspirin, 26% [121 of 473] vs. 30% [140 of 473];
hazard ratio, 0.57; 95% CI, 0.41 to 0.78). Enoxaparin showed similar associations based on the multivariable analysis (hazard ratio, 0.82; 95% CI, 0.69
to 0.97; corrected CI, 0.61 to 1.05) and propensity score–matching analysis
(with vs. without enoxaparin, 25% [87 of 347] vs. 34% [117 of 347]; hazard
ratio, 0.53; 95% CI, 0.367 to 0.77).
Xu Zhao, M.D., Chan Gao, M.D., Ph.D.,
Feng Dai, Ph.D., Miriam M. Treggiari, M.D., Ph.D., M.P.H.,
Ranjit Deshpande, M.D., F.C.C.M., Lingzhong Meng, M.D.
Anesthesiology 2021; 135:1076–90
What We Already Know about This Topic
• While the treatment of critically ill COVID-19 patients has improved,
mortality rates remain high
What This Article Tells Us That Is New
• In a retrospective cohort consisting of 2,070 critically ill COVID-19
patients treated in six hospitals, multivariable regression analysis
showed lower in-hospital mortality associated with apixaban, aspirin, or enoxaparin treatment
• Propensity score–matching analyses demonstrated lower mortality
for patients receiving apixaban (27% [96 of 360] vs. 37% [133
of 360]), aspirin (26% [121 of 473] vs. 30% [140 of 473]), or
enoxaparin (25% [87 of 347) vs. 34% [117 of 347]) compared to
Particular challenge of COVID-19 treatment is the
high mortality, especially among critically ill patients.
Although the mortality rate was estimated to be ~50%
among critically ill COVID-19 patients in the early stage
of the pandemic,1 a study performed at a later stage of the
pandemic showed a downward trend of mortality rates
from ~44% to ~19%.2 Effective treatments might be one
factor responsible for this decline. Continuous efforts in
Conclusions: Consistent with the known hypercoagulability in severe
COVID-19, the use of apixaban, enoxaparin, or aspirin was independently
associated with lower mortality in critically ill COVID-19..
is less effective
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