Abstract
Venous thromboembolism (VTE) remains a major cause of preventable morbidity and mortality.
Prophylaxis with anticoagulation is limited by bleeding risk, contraindications, and
patient-specific factors. Interest has therefore grown in alternative or adjunctive
nonanticoagulant strategies that can mitigate thrombotic risk without increasing bleeding
complications. Aspirin has demonstrated efficacy in both primary and secondary prevention
of VTE. Most studies and trials have been undertaken in an orthopaedic population
but with favorable safety profile. Statins have been shown to reduce VTE incidence
without increased bleeding in several trials. Metformin appears to reduce prothrombotic
mechanisms in type 2 diabetes. Observational studies have suggested its use to lower
VTE risk. However, randomized data are lacking. Glucagon-like peptide 1 receptor agonists
(GLP-1 RAs) have been shown to reduce weight, improve metabolic control, and possess
anti-inflammatory effects. Evidence suggests GLP-1 RAs may reduce VTE risk. However,
findings are inconsistent across observational and trial-based analyses. Other emerging
alternatives include hydroxychloroquine, proprotein convertase subtilisin/kexin type
9 (PCSK9) inhibitors (post hoc analyses of cardiovascular trials suggesting lower
VTE rates potentially via lipoprotein (a) reduction), sodium-glucose cotransporter-2
inhibitors (overall neutral in meta-analyses of randomized control trials with some
real-world evidence vs. comparators), and renin–angiotensin–aldosterone system modulators
(mixed observational data and no trial-proven benefit). Uncertainties remain regarding
optimal patient selection, duration of prophylaxis, and their role in combination
with standard anticoagulation across these drug classes. Further studies/trials are
warranted to define the efficacy, safety, and guideline positioning of these agents
in diverse patient populations.
Keywords
ACE inhibitor - anticoagulation - aspirin - GLP-1 RA - hydroxychloroquine - metformin
- PCSK9 inhibitor - RAAS - SGLT-2 inhibitor - statins - venous thromboembolism - VTE
