Modernising Acute PE and VTE Management: Meta-Analysis of Newer Anticoagulants Versus Traditional Therapy on...

Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism (PE), is a leading cause of cardiovascular morbidity and mortality. While vitamin K antagonists (VKAs) and low molecular weight heparins (LMWHs) have long served as the standard of care, non-vitamin K antagonist oral anticoagulants, particularly factor Xa inhibitors, have emerged as promising alternatives due to their favourable pharmacokinetic profiles and ease of use. This meta-analysis aimed to evaluate the efficacy and safety of factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban) compared with VKAs or LMWHs in treating acute VTE and PE, including recurrence prevention and mortality outcomes.

A systematic review and meta-analysis were conducted in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 guidelines. Seven randomised controlled trials comprising 25,510 patients were included. Outcomes assessed included VTE recurrence, PE recurrence, and all-cause mortality. Subgroup analyses examined effects in cancer and non-cancer-associated VTE, VTE in renal impairment, VTE-related mortality, bleeding-related mortality, and major bleeding in cancer, non-cancer, and solid tumours. Statistical analyses were performed using a random-effects model.

Factor Xa inhibitors were associated with a statistically significant 15% reduction in VTE recurrence (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.72-0.99; p=0.04). In cancer-associated VTE, they significantly reduced recurrence risk by 24% (HR 0.76; 95% CI 0.59-0.98). In patients without cancer, a non-significant 10% reduction was observed (HR 0.90; 95% CI 0.76-1.06). Major bleeding was significantly lower in patients without cancer (HR 0.76; 95% CI 0.58-0.99), while no significant difference was noted in cancer-associated VTE or solid tumour subgroups. Factor Xa inhibitors significantly reduced bleeding-related mortality by 49% (HR 0.51; 95% CI 0.26-0.99), but showed no difference in VTE-specific or all-cause mortality.

Factor Xa inhibitors are effective and safe alternatives to traditional anticoagulants for most patients with acute VTE. They significantly reduce VTE recurrence, particularly in patients with cancer and bleeding-related mortality. Major bleeding was significantly less in the non-cancer subgroup. These findings support their use as first-line therapy in appropriately selected patients, with consideration of individual bleeding risk, cancer type, renal function, and treatment setting.