Therapeutic Anticoagulation Is Associated with Decreased Mortality in Mechanically Ventilated COVID-19 Patients

Abstract

Objective: To evaluate differences in morbidity and mortality among mechanically ventilated patients with COVID-19 treated with therapeutic versus prophylactic anticoagulation. Methods: We performed a retrospective review of 245 COVID-19 positive patients admitted to the ICU requiring mechanical ventilation from March 1, 2020 through April 11, 2020 at Mount Sinai Hospital. Patients either received therapeutic anticoagulation for a minimum of 5 days or prophylactic dose anticoagulation. Morbidity and mortality data were analyzed. Results: Propensity score (PS) weighted Kaplan-Meier plot demonstrated a survival advantage (57% vs. 25%) at 35 days from admission to the ICU in patients who received therapeutic anticoagulation for a minimum of 5 days compared to those who received prophylactic anticoagulation during their hospital course. A multivariate Cox proportional hazard regression model with PS weights to adjust for baseline differences found a 79% reduction in death in patients who were therapeutically anticoagulated HR 0.209, [95% CI (0.10, 0.46), p <0.001]. Bleeding complications were similar between both groups. A 26.7% [95% CI (1.16, 1.39), p<0.001] excess mortality was found for each 1 mg/dL rise in serum creatinine over a 21-day period. Conclusions: Therapeutic anticoagulation is associated with a survival advantage among patients with COVID-19 who require mechanical ventilation in the ICU.

Association of anticoagulation dose and survival in hospitalized COVID‐19 patients: A retrospective propensity score‐weighted analysis

“…Frequencies in our cohort are higher, but comparable to those reported by Nadkarni et al (3% and 1.7% for those receiving tAC and pAC respectively, compared to 1.9% in the no AC group) 11 . Trinh et al reported markedly higher rates of bleeding events in critically ill patients, especially in the tAC vs pAC groups (31.7% vs 20.5%; P = .07) 14 . While the benefit of tAC came at the cost of more bleeding, the rate of intracranial bleed as evidenced on cranial imaging was similar between the tAC and no AC groups (1.3% vs 1.1%).…”

“…The first study by Paranjpe et al found similar in‐hospital mortality rates between patients treated with tAC and those who were not (22.5% vs 22.8%), a longer median survival time in the tAC group (21 days vs 14 days), and an association between tAC duration and reduced risk of death (HR, 0.86 per day [95% CI 0.82‐0.89]) 13 . Subsequently, Trinh et al reported a 79% decrease in the risk of death in patients treated with at least 5 days of tAC compared to pAC (HR, 0.209 [95% CI 0.1‐0.46]) in critically ill patients belonging to the same cohort and 14 . Most recently, Nadkarni et al expanded the existing cohort to nearly 4400 subjects and specifically investigated the impact of tAC and pAC compared to patients who did not receive AC.…”

“…Others have also explored the effect of AC in a large cohort of hospitalized COVID‐19 patients and found superior outcomes for those treated with tAC, but the comparison group consisted of patients who either received pAC or no AC, and no conclusions could be reached regarding optimal dosing 13 . Notably, in critically ill patients, a significant association with improved survival in subjects treated with tAC compared to pAC was observed 14 . A subsequent analysis of the same cohort again found superior outcomes with the use of AC, but a direct comparison between tAC and pAC failed to show a significant difference 11…”

The Use of Therapeutic-Dose Anticoagulation and Its Effect on Mortality in Patients With COVID-19: A Systematic Review

“…While only 1 study showed a statistically-significant increase in the bleeding risk among patients treated with therapeutic-dose anticoagulation, 20 2 other studies also showed an increase among those receiving this treatment, although this was not significant. 12,13 A larger sample size in the study could have led to a statisticallysignificant result. Therefore, we propose that the use of therapeutic-dose anticoagulation must be further elucidated in the settings of larger propensity-matched prospective cohorts or randomized controlled trials before its implementation in clinical practice.…”

“…Ultimately, 8 studies were included in the final qualitative synthesis (Figure 1). [12][13][14][15][16][17][18][19][20] The main features of the 8 studies are presented in Table 1.…”