The effect of anticoagulation on clinical outcomes in Novel Coronavirus (COVID-19) Pneumonia in a U.S. Cohort

Abstract

Background

COVID-19 infection is associated with D-dimer elevations, high rates of thrombus formation, and poor clinical outcomes. We sought to determine if empiric therapeutic anticoagulation (AC) affected survival in COVID-19 patients compared to standard prophylactic AC.

Methods

Retrospective analysis of 402 COVID-19 patients hospitalized between March 15 and May 31, 2020 was performed. Clinical outcomes were compared between 152 patients treated with therapeutic AC to 250 patients on prophylactic AC. An elastic net logistic regression was designed to first identify the important variables affecting mortality. These variables were then included as covariates to AC in standard multivariate logistic regression models studying the effect of AC on death. Nonparametric survival analysis was conducted, and Kaplan Meier curves were constructed.

Results

Increased mortality was associated with therapeutic AC [OR 3.42 (2.06, 5.67)]. The log-rank test was statistically significant at p = 0.001 showing higher mortality for patients treated with therapeutic AC compared to prophylactic AC. Subset analysis of critically ill and intubated patients had similar survival curves regardless of AC dose. The log-rank test was not significant even with Prentice modification. For non-ICU patients, the log rank test favoring prophylactic AC disappeared when the analysis was stratified by D-dimer level less or greater than 3 ug/mL. Approximately 9% of patients receiving therapeutic AC experienced clinically significant bleeding or thrombocytopenia, versus 3% in those receiving prophylactic AC.

Conclusions

In our cohort, therapeutic anticoagulation provided no mortality benefit over thromboprophylaxis, independent of co-morbidities or disease severity. More adverse events were observed with therapeutic AC.

Highlights

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  Anticoagulation strategies for patients with COVID-19 infections remain unclear.

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  Outcomes of prophylactic versus therapeutic anticoagulation were compared.

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  In our cohort, therapeutic anticoagulation provided no mortality benefit over thromboprophylaxis.

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  Therapeutic anticoagulation was associated with increased adverse events.