Comparison of the Mortality and Bleeding Risk of Anticoagulant Doses in COVID-19 Patients: A Systematic Review and Meta-analysis

Athaya Ferbiantyo  Purnomo; Mokhamad Fahmi Rizki Syaban; Icha Farihah Deniyati  Faratisha; Firstya Diyah  Ekasiwi; Muthi’ah Adira  Juwono; Nur Hudayana; Edwin  Kinesya; Yusuf  Mannagalli; Erwin Alexander  Pasaribu

doi:10.22146/ijp.2697

Athaya Ferbiantyo Purnomo Department of Urology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia https://orcid.org/0000-0002-4710-4486
Mokhamad Fahmi Rizki Syaban Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia http://orcid.org/0000-0003-4287-2379
Icha Farihah Deniyati Faratisha Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia https://orcid.org/0000-0002-6767-5577
Firstya Diyah Ekasiwi Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia https://orcid.org/0000-0003-3872-260X
Muthi’ah Adira Juwono Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia https://orcid.org/0000-0002-4976-8577
Nur Hudayana Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia https://orcid.org/0000-0001-9324-1185
Edwin Kinesya Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia https://orcid.org/0000-0002-5210-9089
Yusuf Mannagalli Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia https://orcid.org/0000-0003-1308-519X
Erwin Alexander Pasaribu Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia https://orcid.org/0000-0003-4675-0117

Keywords: Anticoagulants, COVID-19, Bleeding, Mortality

Abstract

Anticoagulant therapy becomes critical to preventing further complications caused by the hypercoagulative state in COVID-19 patients. The optimal dose and time-dependent administration of anticoagulants remains unknown. The purpose of this study was to determine the mortality and bleeding risks of anticoagulants administered to COVID-19 patients. We collected data from articles that compared prophylactic and therapeutic anticoagulants in COVID-19 patients recorded online from studies that were published around 2020 to 2021. We were taking the articles from a scientific database such as ScienceDirect, Cochrane, ProQuest, PubMed, and Google Scholar based on the inclusion criteria. Data analysis was conducted using Review Manager Version 5.4.1 (Cochrane, Copenhagen, Denmark) using Mantel-Haenzel statistical method for categorical data to measure Relative Risk (RR) and 95% Confidence Interval (CI). We use a random-effect analysis model if P for heterogeneity (pHet <0.1) and a fixed-effect analysis model if pHet ≥0.1. Based on time dependent-manner, therapeutic anticoagulant showed no benefit in reducing mortality (RR = 0.69; 95% CI = 0.47 to 1.02). Beside, based on dose-dependent manner, prophylactic anticoagulant was found beneficial to prevent mortality (RR = 0.49; CI 95%; p = 0.02) compared to therapeutic. Therapeutic anticoagulants also showed higher risk of bleeding (RR = 0.27; CI 95%; p < 0.000001) compared to prophylactic. Therapeutic have no significantly benefit over prophylactic dose in reducing mortality rates. Therapeutic anticoagulant has a higher risk of bleeding in patients with COVID-19. Administer prophylactic dose is recommended due to the fewer side effects compared to the therapeutic dose.

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