Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial

Abstract

Background: Thrombotic complications are considered among the main extrapulmonary manifestations of COVID-19. The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. Methods: This manuscript reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. Results: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]; 62 (50, 71) years; 237 (42.2%) women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate-dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, P=0.11). No significant differences were observed between the two groups for other efficacy outcomes, or in the landmark analysis from days 31-90. Overall, there were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24, P=0.33). Conclusion: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

The effect of higher-intensity dosing of anticoagulation on the clinical outcomes in hospitalized patients with COVID-19: A meta-analysis of randomized controlled trials

“…Our systematic literature search retrieved 1881 hits, of which 1045 were unique (titles retrieved after removing duplications). After screening against inclusion and exclusion criteria, eight randomized controlled trials [ [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] ] were included ( Fig. 1 ), with a total of 5405 patients (2746 patients randomized to the intermediate or therapeutic anticoagulation group, and 2659 patients randomized to the prophylactic anticoagulation group).…”

“…1 ), with a total of 5405 patients (2746 patients randomized to the intermediate or therapeutic anticoagulation group, and 2659 patients randomized to the prophylactic anticoagulation group). Four of the included randomized trials in this systematic review and meta-analysis were from Iran (n = 1) [ 7 ], the United States (n = 2) [ 8 , 12 ], and Brazil (n = 2) [ 5 , 9 ], respectively, and one of the included randomized trial [ 11 ] was a global trial performed in six countries. In contrast, the remaining two randomized trials [ 6 , 10 ] were international multiplatform randomized controlled trials.…”

“…Details of the included studies are shown in Table 1 . Six randomized trials [ 5 , 6 , [9] , [10] , [11] , [12] ] compared therapeutic-dose anticoagulation against prophylactic-dose anticoagulation, while the other two trials [ 7 , 8 ] compared intermediate-dose anticoagulation against prophylactic-dose anticoagulation.

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Acquired Autoimmune Hemophilia Following SARS-CoV-2 Vaccines: Dual-Drug Effects on Blood Coagulation and the Scylla and Charybdis Phenomenon

“…24 Administration of anticoagulants is of huge importance for thrombotic disease prevention in COVID-19 patients, and heparins (unfractionated or low-molecular weight heparins) are the currently recommended agents for hospitalized COVID-19 patients. 25 , 26 Nevertheless, excessive doses and/or an accumulative effect of heparins may favor bleeding, mainly in the hemorrhagic phase of the infection disease when multiorgan failure also occurs. Therefore, from patients' point of view, anticoagulants and SARS-CoV-2 vaccines share their capacity to induce thrombosis as well as bleeding.…”

COVID-19-assoziierte Koagulopathie

“…[12]. Auch im 90-Tage-Follow-up änderte sich diese Schlussfolgerung nicht [13]. Für Patienten mit einem leichten bzw.…”