Harsini Raaja Sulochana, Yufan Yang, Laura Bindila, Ioannis T Farmakis, Stavros V Konstantinides, Luca Valerio, Philipp S Wild, Vincent Ten Cate
The available evidence suggests potential benefit of LLT+AC combination therapy over AC monotherapy, with respect to both safety and efficacy, though further evidence from RCTs is necessary to generate conclusive evidence.
BACKGROUND: It is unclear whether combined anticoagulation (AC) plus lipid-lowering therapies (LLTs) enhance AC efficacy for venous thromboprophylaxis while maintaining an acceptable safety profile.
METHODS: A systematic literature search was conducted in PubMed, Cochrane CENTRAL library, and Web of Science, including randomized controlled trials (RCTs) and observational studies published until May 2026. The associations of LLT+AC vs. AC monotherapy with efficacy outcomes (i.e., recurrent venous thromboembolism [rVTE] and post-thrombotic syndrome [PTS] risk), safety outcomes (i.e., major bleeding), and other outcomes were analyzed. A Bayesian random-effects meta-analysis was used to aggregate study estimates (95% credible interval [CrI]) and calculate the posterior probability of benefit (relative risk [RR] < 1).
FINDINGS: The search yielded 28 (17 observational studies and 11 RCTs) studies eligible for meta-analysis. The pooled effect size of LLT+AC vs. AC alone for rVTE was RR = 0.73 [95% CrI: 0.58; 1.05, P(RR < 1) = 0.97]. In addition, there was a 17% lower risk observed for PTS [RR = 0.83, 95% CrI: 0.40; 1.59, P(RR < 1) = 0.74]. Major bleeding risk was 15% lower [RR = 0.85, 95% CrI: 0.76; 0.96, P(RR < 1) = 0.99]. Combined LLT+AC reduced D-dimer [log SMD = -0.15; 95% CrI: -0.43; 0.13, P(SMD < 0) = 0.88] and C-reactive protein levels [log SMD = -0.86; 95% CrI: -1.48; -0.08; P(SMD < 0) = 0.98] relative to AC monotherapy.
CONCLUSIONS: The available evidence suggests potential benefit of LLT+AC combination therapy over AC monotherapy, with respect to both safety and efficacy, though further evidence from RCTs is necessary to generate conclusive evidence.
FUNDING: DIASyM research core (BMBF 031L0219).