Statins and prevention of venous thromboembolism: Myth or reality?

Abstract

The pleiotropic effects of statins, beyond their cholesterol-lowering properties, are much debated. In primary prevention, several observational cohort and case-control studies appear to show that statins reduce the incidence of venous thromboembolism by about 30%. In a single randomized placebo-controlled clinical trial (JUPITER), which included 17,000 patients, rosuvastatin 20mg/day reduced the risk of venous thromboembolism by 43%. However, these patients were at low risk of venous thromboembolism, and the frequency of the event was, in principle, low. In secondary prevention, several observational studies and post-hoc analyses of randomized clinical trials have suggested that statins may prevent recurrence of venous thromboembolism. However, none of these studies had enough scientific weight to form the basis of a recommendation to use statins for secondary prevention. The putative preventive effect of statins appears to be independent of plasma cholesterol concentration and could be a pharmacological property of the statin class, although a dose-effect relationship has not been demonstrated. The mechanism through which statins might prevent venous thrombosis is thought to involve their anti-inflammatory and antioxidant effects or perhaps a more specific action, by blocking the degradation of antithrombotic proteins. A mechanism involving the action of statins on interactions between risk factors for atherosclerosis and venous thromboembolism is supported by some studies, but not all. In the absence of firm evidence, statins cannot currently be recommended for primary or secondary prevention of venous thromboembolism.

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

“…From this perspective, our findings corroborate and reinforce the differences observed in the previous meta-analysis while adding also evidence from "head-to-head" RCTs [7]. relationship has not been demonstrated [35]. Our study indicates a relative risk reduction of 37% per 1 mmol/L of LDL-c, which is higher than estimates for atherothrombotic events.…”

Statins and secondary prevention of venous thromboembolism: pooled analysis of published observational cohort studies

“…Moreover, our estimated ARR was based on the assumption that recurrent VTE occurs at a constant rate over time. Secondary prevention of VTE may be another potential indication of statins; however, to echo a previous report by Gaertner et al, 31 it is still too early to make any guideline recommendations based on the current evidence. Well-designed intervention studies are now needed to corroborate this evidence and the benefits of statins also need to be balanced against the potential for harm.…”

Protective Effects of Statins Administration in European and North American Patients Infected with COVID-19: A Meta-Analysis

“…As such, statins are not clinically indicated for primary or secondary prevention of venous thromboembolism. 59,60 Thus, the beneficial effects of statins in COVID-19 are more likely to be attributed to its anti-inflammatory properties (as well as improvement in endothelial function) than to any significant antithrombotic direct effect.…”