Empiric use of anticoagulation in hospitalized patients with COVID-19: a propensity score-matched study of risks and benefits

Abstract

Background Hospitalized patients with COVID-19 demonstrate a higher risk of developing thromboembolism. Anticoagulation (AC) has been proposed for high-risk patients, even without confirmed thromboembolism. However, benefits and risks of AC are not well assessed due to insufficient clinical data. We performed a retrospective analysis of outcomes from AC in a large population of COVID-19 patients. Methods We retrospectively reviewed 1189 patients hospitalized for COVID-19 between March 5 and May 15, 2020, with primary outcomes of mortality, invasive mechanical ventilation, and major bleeding. Patients who received therapeutic AC for known indications were excluded. Propensity score matching of baseline characteristics and admission parameters was performed to minimize bias between cohorts. Results The analysis cohort included 973 patients. Forty-four patients who received therapeutic AC for confirmed thromboembolic events and atrial fibrillation were excluded. After propensity score matching, 133 patients received empiric therapeutic AC while 215 received low dose prophylactic AC. Overall, there was no difference in the rate of invasive mechanical ventilation (73.7% versus 65.6%, p = 0.133) or mortality (60.2% versus 60.9%, p = 0.885). However, among patients requiring invasive mechanical ventilation, empiric therapeutic AC was an independent predictor of lower mortality (hazard ratio [HR] 0.476, 95% confidence interval [CI] 0.345–0.657, p < 0.001) with longer median survival (14 days vs 8 days, p < 0.001), but these associations were not observed in the overall cohort (p = 0.063). Additionally, no significant difference in mortality was found between patients receiving empiric therapeutic AC versus prophylactic AC in various subgroups with different D-dimer level cutoffs. Patients who received therapeutic AC showed a higher incidence of major bleeding (13.8% vs 3.9%, p < 0.001). Furthermore, patients with a HAS-BLED score of ≥2 had a higher risk of mortality (HR 1.482, 95% CI 1.110–1.980, p = 0.008), while those with a score of ≥3 had a higher risk of major bleeding (Odds ratio: 1.883, CI: 1.114–3.729, p = 0.016). Conclusion Empiric use of therapeutic AC conferred survival benefit to patients requiring invasive mechanical ventilation, but did not show benefit in non-critically ill patients hospitalized for COVID-19. Careful bleeding risk estimation should be pursued before considering escalation of AC intensity.

Risk Factors for Venous Thromboembolism in Severe COVID-19: A Study-Level Meta-Analysis of 21 Studies

“…Indeed, the stratifications of VTE risk may increase the benefit–risk ratio of primary prevention of thrombosis using intermediate or therapeutic anticoagulant dose. This concept is supported by a retrospective monocentric study including critically ill COVID-19 patients, suggesting that this subgroup of patients with elevated D-dimer levels requiring mechanical ventilation—two risk factors identified in the present meta-analysis—may benefit from therapeutic anticoagulation [ 43 ]. Although subgroup analysis from recent trials did not show any interaction between D-dimer levels and the efficacy of full-dose anticoagulation, critically ill COVID-19 patients are likely to represent a highly heterogeneous group of patients with a diverse risk of VTE and bleeding.…”

Effect of therapeutic versus prophylactic anticoagulation therapy on clinical outcomes in COVID-19 patients: a systematic review with an updated meta-analysis

“…Eight of the 11 RCTs compared therapeutic versus prophylactic doses of anticoagulants, and three trials compared moderate therapeutic versus prophylactic doses of anticoagulants. Seven of the 17 OBs trials involved critically ill patients [ 29 , 31 – 33 , 36 , 41 , 42 ], and ten involved non-critically ill patients [ 8 , 28 , 30 , 34 , 35 , 37 – 40 , 43 ]. The outcomes of the 28 clinical studies are summarized in Tables 3 and 4 .…”

Intermediate-to-therapeutic versus prophylactic anticoagulation for coagulopathy in hospitalized COVID-19 patients: a systemic review and meta-analysis

“…Of the forty-two included studies, 6 studies [ 34 – 39 ] were RCTs and 36 studies [ 40 – 75 ] were cohort studies. Thirteen studies [ 34 , 38 , 39 , 41 , 43 , 52 , 55 , 58 , 61 , 64 , 67 , 69 , 70 ] were performed exclusively in patients admitted to ICU.…”

“…Thirteen studies [ 34 , 38 , 39 , 41 , 43 , 52 , 55 , 58 , 61 , 64 , 67 , 69 , 70 ] were performed exclusively in patients admitted to ICU. Eighteen studies [ 34 , 40 , 42 , 48 , 51 , 53 – 55 , 57 , 62 – 66 , 68 – 70 , 73 ] reported results from the United States and two [ 37 , 38 ] were international studies. Other studies originated from eleven countries ( Italy [ 47 , 49 , 56 , 58 , 60 , 72 , 75 ], France [ 41 , 61 , 67 ], Brazil [ 35 , 36 ], England [ 59 ], Greek [ 46 ], China [ 45 ], Japan [ 43 ], Mexico [ 44 ], United Arab Emirates [ 52 , 71 ], Turkey [ 74 ], Iran [ 39 ] and Spain [ 50 ] ).…”