Full-dose heparin anticoagulation as prevention for COVID-19 disease progression in non-critically ill patients: An up-to-date brief meta-analysis

This systematic review and meta-analysis aims to investigate the effect of heparin full-dose anticoagulation on preventing COVID-19 disease progression in non-critically ill COVID-19 adult patients in accordance with the Cochrane methodology and the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed/Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and Clinicaltrials.gov (from inception to September 2025). Multicenter randomized controlled trials (mRCTs) comparing full-dose heparin anticoagulation with no full-dose anticoagulation (including prophylactic or intermediate-dose anticoagulation with heparin). The primary outcome was the need for invasive mechanical ventilation. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the number CRD42022348993. We included 6 mRCTs in the analysis, randomizing a total of 5777 COVID-19 patients. The rate of need for invasive mechanical ventilation was lower in patients treated with full-dose heparin at 7.9% (226/2842) compared with 9.5% (279/2935) in those receiving prophylactic or intermediate-dose ([RR] = 0.81; 95% [CI] = 0.68–0.96; P = 0.01). The absolute risk (AR) of requiring invasive mechanical ventilation was 77 per 1.000 in patients treated with full-dose heparin, compared with 95 per 1.000 in patients treated with prophylactic or intermediate-dose heparin. According to our updated data analysis of high-quality mRCTs, full-dose anticoagulation with heparin can be considered an important strategy to prevent disease progression and the need for invasive organ support in hospitalized non-critically ill COVID-19 patients.