Meta-analysis finds intensified anticoagulation had no impact on brief time period mortality amongst hospitalized COVID-19 sufferers

A latest systematic assessment and meta-analysis posted to the medRxiv* preprint server evaluated the protection and efficacy of intensified anticoagulation remedy in coronavirus illness 2019 (COVID-19) sufferers.

Study: Efficacy and safety of intensified versus standard prophylactic anticoagulation therapy in patients with Covid-19: a systematic review and meta-analysis. Image Credit: tigerder/Shutterstock
Research: Efficacy and security of intensified versus commonplace prophylactic anticoagulation remedy in sufferers with Covid-19: a scientific assessment and meta-analysis. Picture Credit score: tigerder/Shutterstock


COVID-19 pneumonia is related to a hypercoagulable state that outcomes from an intense prothrombotic inflammatory response and endothelial perturbation and progresses into COVID-19-associated coagulopathy. This syndrome is marked by elevated D-dimer and fibrinogen ranges and pulmonary microvascular thrombosis, which is linked to the worst medical end result of COVID-19.

Research have noticed an elevated threat of thrombosis in COVID-19 sufferers, notably these with extreme COVID-19. The chance of venous thrombosis is excessive even when commonplace prophylactic anticoagulation remedy is used. A couple of (non-comparative) research steered that using an intensified anticoagulant dose would possibly decrease thrombotic problems. Randomized managed trials (RCTs) famous inconsistent results of utilizing intensified anticoagulation therapies on COVID-19 outcomes.

The assessment

The authors looked for RCTs that in contrast intensified anticoagulant dosing to plain prophylactic dosing for COVID-19 sufferers. The intensified dose was outlined as a therapeutic or intermediate-dose viz, 1mg/kg enoxaparin as soon as daily or equal. There was no bias in deciding on papers, i.e., anticoagulant kind, publication standing (printed or preprint), or language.

An digital search was completed on September 19, 2021, and January 19, 2022, utilizing MEDLINE, Scopus, COVID-19 database of the World Well being Group (WHO), and Cochrane library. WHO trial registry community and medical trials databases had been screened to retrieve not too long ago concluded or ongoing trials, whereas PROSPERO was used to acquire systematic opinions.

The core goal was finding out all-cause mortality upon discharge or follow-up. Venous thromboembolism (VTE), arterial thrombosis, different thrombotic occasions, and dying had been included for assessing remedy efficacy. The essential security end result measured was non-major bleeding and different bleeding occasions. Furthermore, the results of intensified anticoagulation had been analyzed on days when respiratory and organ help was required.

The researchers screened greater than 2400 data and finalized 11 research that matched the inclusion eligibility comprising information on 5873 adults with laboratory-confirmed COVID-19 diagnoses. Amongst these had been 5 intensive care unit (ICU)-based research on 1979 critically ailing sufferers; 5 research had been on 3616 hospitalized (basic ward) sufferers, and one research reported outcomes on 278 outpatients. 9 research in contrast using unfractionated heparin (UFN), therapeutic low molecular weight heparin (LMWH), apixaban, or rivaroxaban to plain thromboprophylaxis, and two others had been ICU-based research which in contrast enoxaparin (intermediate dose) to a normal dose of enoxaparin.

Among the many 11 research, 41% had been feminine; the median age ranged between 52 – 71 years. Of those, 38% obtained antiviral medicine at baseline, in distinction to 64% who obtained corticosteroids. Individuals with diabetes constituted 30% of the pattern, whereas 45% reported hypertension. Persistent cardiac illness was noticed in 8%, whereas continual lung illness was documented in 17%.

All-cause mortality was noticed in 16.7% within the intensified anticoagulation cohort whereas 17.9% in the usual prophylactic group. The authors famous that intensified anticoagulation remedy was not related to decreased mortality threat. VTE threat was low with intensified anticoagulation remedy in comparison with commonplace prophylaxis. Moreover, intensified anticoagulation was related to a decreased threat of composite thrombotic end result or dying.

General, thrombosis threat was decrease with intensified remedy, however there was no proof to counsel the identical for arterial thrombosis. Main bleeding occasions had been extra with intensified remedy when in comparison with prophylaxis, with 1.3% within the intensified remedy cohort present process bleeding in distinction to 1.3% within the prophylactic group. Notably, different non-major bleeding and any bleeding occasions had elevated dangers with intensified anticoagulation.

A slight mortality lower was famous inside the basic ward inpatients with excessive heterogeneity and low precision. Intermediate and therapeutic dosing had no vital variations in mortality, though heterogeneity was substantial amongst trials with therapeutic dosing.


The present meta-analysis protecting information from 11 RCTs on 5873 people noticed that intensified anticoagulation remedy had no impact on mortality for hospitalized COVID-19 sufferers. Nonetheless, intensified remedy was related to a decreased threat of VTE, together with composite VTE outcomes and dying, however with an elevated threat of main bleeding.

Regardless of a big discount in VTE occasions with an intensified anticoagulant dosing routine, survival profit was not noticed. One of many believable causes for the shortage of mortality discount might be that the excessive threat of main bleeding related to commonplace thromboprophylaxis and extra 74% elevation with intensified remedy may offset mortality discount on account of VTE. Based mostly on the observations, it’s not justifiable to introduce intensified anticoagulant remedy for non-critically ailing COVID-19 sufferers.

*Necessary discover

medRxiv publishes preliminary scientific reviews that aren’t peer-reviewed and, subsequently, shouldn’t be considered conclusive, information medical observe/health-related conduct, or handled as established info.

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