Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: A propensity score-matched analysis

Abstract

Thrombotic complications occur at high rates in hospitalized patients with COVID-19, yet the impact of intensive antithrombotic therapy on mortality is uncertain. We examined in-hospital mortality with intermediate- compared to prophylactic-dose anticoagulation, and separately with in-hospital aspirin compared to no antiplatelet therapy, in a large, retrospective study of 2785 hospitalized adult COVID-19 patients. In this analysis, we established two separate, nested cohorts of patients (a) who received intermediate- or prophylactic-dose anticoagulation ("anticoagulation cohort", N = 1624), or (b) who were not on home antiplatelet therapy and received either in-hospital aspirin or no antiplatelet therapy ("aspirin cohort", N = 1956). To minimize bias and adjust for confounding factors, we incorporated propensity score matching and multivariable regression utilizing various markers of illness severity and other patient-specific covariates, yielding treatment groups with well-balanced covariates in each cohort. The primary outcome was cumulative incidence of in-hospital death. Among propensity score-matched patients in the anticoagulation cohort (N = 382), in a multivariable regression model, intermediate- compared to prophylactic-dose anticoagulation was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.518 [0.308-0.872]). Among propensity-score matched patients in the aspirin cohort (N = 638), in a multivariable regression model, in-hospital aspirin compared to no antiplatelet therapy was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.522 [0.336-0.812]). In this propensity score-matched, observational study of COVID-19, intermediate-dose anticoagulation and aspirin were each associated with a lower cumulative incidence of in-hospital death.

FIGURE 1

Cumulative incidence of in‐hospital death among propensity score‐matched patients (A) in the anticoagulation cohort, comparing intermediate‐ versus prophylactic‐dose anticoagulation, and (B) in the aspirin cohort admitted after May 18, 2020, comparing in‐hospital aspirin versus no antiplatelet therapy. (A) Patients in the anticoagulation cohort were propensity score matched for age, maximum D‐dimer level, admission Rothman Index score, body mass index, and African‐American race using a random number seed and a caliper width of 0.25. (B) Patients in the aspirin cohort admitted after May 18 were propensity score matched for age, maximum D‐dimer level, and admission Rothman Index score. In each panel, p values from Gray's test describe differences in cumulative incidence functions between treatment groups [Color figure can be viewed at wileyonlinelibrary.com]