Is the lower risk of venous thromboembolism with statins related to low-density-lipoprotein reduction? A network meta-analysis and meta-regression of randomised controlled trials

Background and aims: Meta-analyses of randomised controlled trials (RCTs) have suggested a possible benefit of statin treatment on the risk of venous thromboembolism (VTE), with potential differences by type and dose of statins. We aimed to assess differences among statins and to investigate the relationship between risk of VTE and reduction of LDL-cholesterol (LDL-c) levels. Methods: We electronically searched, through November 29, 2017, RCTs comparing a statin with either placebo or another statin treatment, including 100 or more adult participants, and lasting at least 24 weeks. Data on first VTE events and LDL-c was analysed with a network meta–analysis and a meta–regression. Results: Thirty RCTs (159,058 participants; 1431 events) were included, with 28 reporting LDL-c data. Network meta-analysis indicated a larger benefit for rosuvastatin compared to placebo and other statins; 50% of the effect of statins on VTE risk reduction, however, was explained by their different potencies in lowering LDL-c. The risk reduction in VTE was proportional to LDL-c decrease (37% relative lower risk per each 1 mmol/L reduction in LDL-c), without an apparent threshold. A reduction of 1 mmol/L in LDL-c would translate in 37 less VTE events per year in 100,000 people in UK, corresponding to 3162 prevented episodes per year in people between 50 and 59 years. Conclusions: In RCTs with statin treatment, the reduction of VTE risk was only partially related to LDL-c reduction and the benefit was larger than that observed for atherothrombotic risk. Further RCTs are warranted to clarify the relationship between statin, lipid modifications, and VTE risk.