PMID- 34539396 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240403 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 12 DP - 2021 TI - A Systematic Review and a Meta-Analysis Comparing Prophylactic and Therapeutic Low Molecular Weight Heparins for Mortality Reduction in 32,688 COVID-19 Patients. PG - 698008 LID - 10.3389/fphar.2021.698008 [doi] LID - 698008 AB - Background: Antithrombotic treatment, including low molecular weight heparin (LMWH) or unfractionated heparin (UFH), has been proposed as a potential therapy for coronavirus disease 2019 (COVID-19) to lower diffuse intravascular clotting activation. However, it is unclear whether prophylactic or therapeutic doses have similar efficacy in reducing mortality. Methods: We performed a systematic review (PROSPERO registration CRD42020179955) and meta-analysis including observational cohort studies and randomized controlled trials (RCT) evaluating the effectiveness of heparins (either LMWH, UFH, or fondaparinux) in COVID-19 patients. Heparin treatment was compared to no anticoagulation. A subgroup analysis on prophylactic or therapeutic doses compared to no anticoagulation was performed. Prophylactic dose was also compared to full dose anticoagulation. Primary endpoint was all-cause mortality. Secondary endpoints were major bleeding and length of hospital stay (LOS). Results: 33 studies (31 observational, 2 RCT) were included for a total overall population of 32,688 patients. Of these, 21,723 (66.5%) were on heparins. 31 studies reported data on all-cause mortality, showing that both prophylactic and full dose reduced mortality (pooled Hazard Ratio [HR] 0.63, 95% confidence interval [CI] 0.57-0.69 and HR 0.56, 95% CI 0.47-0.66, respectively). However, the full dose was associated with a higher risk of major bleeding (Odds Ratio [OR] 2.01, 95% CI 1.14-3.53) compared to prophylactic dose. Finally, LOS was evaluated in 3 studies; no difference was observed between patients with and without heparins (0.98, -3.87, 5.83 days). Conclusion: Heparin at both full and prophylactic dose is effective in reducing mortality in hospitalized COVID-19 patients, compared to no treatment. However, full dose was associated with an increased risk of bleeding. Systematic Review Registration: https://clinicaltrials.gov/, identifier CRD42020179955. CI - Copyright (c) 2021 Giossi, Menichelli, Pani, Tratta, Romandini, Roncato, Nani, Schenardi, Diani, Fittipaldo, Farcomeni, Scaglione and Pastori. FAU - Giossi, Riccardo AU - Giossi R AD - Postgraduate School of Clinical Pharmacology, Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. FAU - Menichelli, Danilo AU - Menichelli D AD - Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy. FAU - Pani, Arianna AU - Pani A AD - Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. FAU - Tratta, Elena AU - Tratta E AD - Postgraduate School of Clinical Pharmacology, Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. AD - Central Pharmacy, ASST Spedali Civili, Brescia, Italy. FAU - Romandini, Alessandra AU - Romandini A AD - Postgraduate School of Clinical Pharmacology, Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. FAU - Roncato, Rossana AU - Roncato R AD - Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy. FAU - Nani, Alessandro AU - Nani A AD - Postgraduate School of Clinical Pharmacology, Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. FAU - Schenardi, Paolo AU - Schenardi P AD - Postgraduate School of Clinical Pharmacology, Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. FAU - Diani, Erika AU - Diani E AD - Postgraduate School of Clinical Pharmacology, Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. AD - Pharmacy Unit, ASST Papa Giovanni XXIII, Bergamo, Italy. FAU - Fittipaldo, Veronica Andrea AU - Fittipaldo VA AD - Oncology Department, Mario Negri Institute for Pharmacological Research IRCCS, Milano, Italy. FAU - Farcomeni, Alessio AU - Farcomeni A AD - Department of Economics and Finance, University of Rome "Tor Vergata", Rome, Italy. FAU - Scaglione, Francesco AU - Scaglione F AD - Postgraduate School of Clinical Pharmacology, Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. AD - Department of Laboratory Medicine, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Pastori, Daniele AU - Pastori D AD - Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy. LA - eng PT - Journal Article DEP - 20210902 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8443784 OTO - NOTNLM OT - COVID-19 OT - LMWH OT - SARS-CoV2 OT - bleeding OT - heparin OT - mortality OT - thromboembolism COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/09/21 06:00 MHDA- 2021/09/21 06:01 PMCR- 2021/09/02 CRDT- 2021/09/20 06:01 PHST- 2021/04/20 00:00 [received] PHST- 2021/08/05 00:00 [accepted] PHST- 2021/09/20 06:01 [entrez] PHST- 2021/09/21 06:00 [pubmed] PHST- 2021/09/21 06:01 [medline] PHST- 2021/09/02 00:00 [pmc-release] AID - 698008 [pii] AID - 10.3389/fphar.2021.698008 [doi] PST - epublish SO - Front Pharmacol. 2021 Sep 2;12:698008. doi: 10.3389/fphar.2021.698008. eCollection 2021.