Enoxaparin for thromboprophylaxis in hospitalized COVID‐19 patients: The X‐COVID‐19 Randomized Trial

Abstract

Background It is uncertain whether higher doses of anticoagulants than recommended for thromboprophylaxis are necessary in COVID‐19 patients hospitalized in general wards Methods This is a multicentre, open‐label, randomized trial performed in 9 Italian centres, comparing 40 mg b.i.d. versus 40 mg o.d. enoxaparin in COVID‐19 patients, between April 30 2020 and April 25 2021. Primary efficacy outcome was in‐hospital incidence of venous thromboembolism (VTE): asymptomatic or symptomatic proximal deep vein thrombosis (DVT) diagnosed by serial compression ultrasonography (CUS), and/or symptomatic pulmonary embolism (PE) diagnosed by computed tomography angiography (CTA). Secondary endpoints included each individual component of the primary efficacy outcome and a composite of death, VTE, mechanical ventilation, stroke, myocardial infarction, admission to ICU. Safety outcomes included major bleeding. Results The study was interrupted prematurely due to slow recruitment. We included 183 (96%) of the 189 enrolled patients in the primary analysis (91 in b.i.d., 92 in o.d.). Primary efficacy outcome occurred in 6 patients (6.5%, 0 DVT, 6 PE) in the o.d. group and 0 in the b.id. group (ARR 6.5, 95% CI: 1.5–11.6). The absence of concomitant DVT and imaging characteristics suggests that most pulmonary artery occlusions were actually caused by local thrombi rather than PE. Statistically nonsignificant differences in secondary and safety endpoints were observed, with two major bleeding events in each arm. Conclusions No DVT developed in COVID‐19 patients hospitalized in general wards, independently of enoxaparin dosing used for thromboprophylaxis. Pulmonary artery occlusions developed only in the o.d. group. Our trial is underpowered and with few events.

Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trial

“…This is in agreement with previous prospective studies, the HEP-COVID, and X-COVID-19 trials showing a low prevalence of asymptomatic proximal DVT of 0% to 2.9% among acutely ill medical patients. 14,17,[30][31][32] In the ICU, we did not find the elevated (5%-23%) risks found by previous prospective studies. [33][34][35][36][37] Our trial has several strengths.…”

COVID‐19 coagulopathy – what should we treat?

“…confirming the de novo nature of the pulmonary thrombi (Morici et al, 2021). A cohort study showed an increasing prevalence of PE with increasing D-dimers, with a 10-fold elevation strongly predictive of PE (Perera et al, 2021).…”

The Role of Heparin in COVID-19: An Update after Two Years of Pandemics

“…An increase in bleeding was also observed [ 69 , 70 , 71 ]. The studies we discussed [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ] and the available meta-analyses [ 62 , 63 , 64 , 65 , 66 ] revealed the need for a tailored anticoagulant therapy. Heparin was shown to reduce mortality both at prophylactic and therapeutic dosages; however, an increase in bleeding was reported [ 72 ].…”

“…Although underpowered, the analysis of 183 patients showed no deep vein thrombosis in COVID-19 hospitalized patients in both groups; however pulmonary embolism was observed only in the prophylactic dose group (six patients). No major bleeding and thrombocytopenia events were reported [ 61 ].…”