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 μg/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.

Pragmatic Recommendations for the Management of Anticoagulation and Venous Thrombotic Disease for Hospitalized Patients with COVID-19 in Low- and Middle-Income Countries

“…It may be that the primary driver of mortality in these patients is the degree of severity of infection rather than initiation of therapeutic anticoagulation. 40 Availability, feasibility, affordability, and safety. Guidelines for chemoprophylaxis for non-COVID-19 cases in LMICs frequently are in accordance with recommendations from HICs.…”

Anticoagulation therapy in COVID-19: Is there a dose-dependent benefit?

“…We read with interest the study by Lynn et al among 402 hospitalized COVID-19 patients, which did not show any survival benefit in those who were administered therapeutic dosage of anticoagulation (AC) compared to standard thromboprophylaxis [ 1 ]. It should be mentioned that the study had retrospective design and therapeutic AC was empirically prescribed mainly to patients with severe COVID-19, especially those admitted to Intensive Care Unit (ICU) [ 1 ].…”

“…We read with interest the study by Lynn et al among 402 hospitalized COVID-19 patients, which did not show any survival benefit in those who were administered therapeutic dosage of anticoagulation (AC) compared to standard thromboprophylaxis [ 1 ]. It should be mentioned that the study had retrospective design and therapeutic AC was empirically prescribed mainly to patients with severe COVID-19, especially those admitted to Intensive Care Unit (ICU) [ 1 ]. Another retrospective study including 4389 COVID-19 patients, showed that the administration of prophylactic or therapeutic AC therapy was associated with lower in-hospital mortality and intubation compared with no AC; however, in a sub-analysis including patients initiating AC ≤48 h from admission, no significant difference was observed between therapeutic and prophylactic AC, despite a trend in favor of the former [ 2 ].…”

“…However, it should be mentioned that in these studies, therapeutic AC was administered empirically or according to protocols taking into consideration adverse parameters related to COVID-19 severity, which in turn might have predicted an unfavorable prognosis. Therefore, the benefit of the therapeutic AC might have been blunted by the severity of COVID-19 in these high-risk patients despite the fact that the authors used a meticulous statistical approach and adjusted for several confounding factors [ [1] , [2] , [3] ].…”

“…Apart from issues regarding the efficacy of the AC treatment, the safety profile of such interventions should be carefully considered. Interestingly, among the abovementioned studies, only in the study by Lynn et al, therapeutic dosage of AC was associated with increased risk of clinically significant bleeding events compared to lower AC dosages [ 1 ]. However, in this study therapeutic AC was more likely to be administered to frail patients with severe COVID-19 which could imply an indication bias.…”