Therapeutic Anticoagulation in Critically Ill Patients with Covid-19 – Preliminary Report

Zarychanski, Ryan

doi:10.1101/2021.03.10.21252749

Cited by 53 publications

(46 citation statements)

References 26 publications

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“…Although there was no difference in hospital survival, standard prophylactic dosing is preferred due to more organ support-free days defined as a composite of death, the number of days free of respiratory organ support and cardiovascular organ support, as well as less major bleeding. 37 Similar findings in critically ill patients have also been published in the INSPIRATION trial that showed no benefit of intermediate doses of anticoagulation compared with prophylactic doses in terms of the composite endpoint of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation or mortality within 30 days. Less major bleeding was also noted in the prophylactic dose arm.…”

Section: Antiplatelet Usesupporting

confidence: 69%

Role of combining anticoagulant and antiplatelet agents in COVID-19 treatment: a rapid review

et al. 2021

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Although primarily affecting the respiratory system, COVID-19 causes multiple organ damage. One of its grave consequences is a prothrombotic state that manifests as thrombotic, microthrombotic and thromboembolic events. Therefore, understanding the effect of antiplatelet and anticoagulation therapy in the context of COVID-19 treatment is important. The aim of this rapid review was to highlight the role of thrombosis in COVID-19 and to provide new insights on the use of antithrombotic therapy in its management. A rapid systematic review was performed using preferred reporting items for systematic reviews. Papers published in English on antithrombotic agent use and COVID-19 complications were eligible. Results showed that the use of anticoagulants increased survival and reduced thromboembolic events in patients. However, despite the use of anticoagulants, patients still suffered thrombotic events likely due to heparin resistance. Data on antiplatelet use in combination with anticoagulants in the setting of COVID-19 are quite scarce. Current side effects of anticoagulation therapy emphasise the need to update treatment guidelines. In this rapid review, we address a possible modulatory role of antiplatelet and anticoagulant combination against COVID-19 pathogenesis. This combination may be an effective form of adjuvant therapy against COVID-19 infection. However, further studies are needed to elucidate potential risks and benefits associated with this combination.

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Section: Antiplatelet Usesupporting

confidence: 69%

Role of combining anticoagulant and antiplatelet agents in COVID-19 treatment: a rapid review

et al. 2021

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“…On the basis of the data summarised in table 1, the multiplatform trial discontinued enrolment for ICU patients on Dec 19, 2020, after an interim analysis and advice from the data and safety monitoring board, because the prespecified futility boundary for the primary endpoint was reached and a potential for harm could not be excluded. 44 As shown in a preprint paper, 45 there were numerically fewer thrombotic events in patients assigned to therapeutic anticoagulation (27 [6%] of 471 vs 49 [10%] of 476 assigned to standard prophylaxis); however, the secondary efficacy outcome of major thrombotic events or death was similar between groups (200 [41%] of 483 vs 211 [43%] of 494, median adjusted odds ratio 1•05, 95% credible interval 0•79-1•41; posterior probability of futility 94•5%). Although the recommendation might be different if prevention of thrombosis was used as the primary outcome, the current outcome reflects morbidity and mortality, which in a pandemic are also more relevant from a health-care system and societal perspective.…”

Section: Icu Patients (Stage 3)mentioning

confidence: 95%

COVID-19-associated coagulopathy and antithrombotic agents—lessons after 1 year

Leentjens¹,

Haaps

Wessels

et al. 2021

The Lancet Haematology

189

180

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“…prophylaxis during the period of hospitalization. 4,25,26 In addition, a preprint report from the multiplatform trial (including REMAP CAP, ACTIV4, and ATTACC) of fully therapeutic anticoagulation versus standarddose prophylaxis in critically ill patients with COVID-19 27 did not suggest a reduction in mortality or the need for organ support with therapeutic anticoagulation. However, these results collectively are in contrast to recommendations from other consensus recommendations for empiric escalated-dose prophylaxis.…”

Section: Standard-dosementioning

confidence: 99%

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

Bikdeli¹,

Talasaz²,

Rashidi³

et al. 2021

Thromb Haemost

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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.

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Therapeutic Anticoagulation in Critically Ill Patients with Covid-19 – Preliminary Report

Cited by 53 publications

References 26 publications

Role of combining anticoagulant and antiplatelet agents in COVID-19 treatment: a rapid review

Role of combining anticoagulant and antiplatelet agents in COVID-19 treatment: a rapid review

COVID-19-associated coagulopathy and antithrombotic agents—lessons after 1 year

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

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