Statins for venous thromboembolism prevention: old dog, new tricks

Abstract

Abstract Background Statins are highly effective in preventing major acute cardiovascular events in the setting of atherosclerotic arterial disease. On the other hand, given their antithrombotic and anti-inflammatory properties, statins may also attenuate patients' odds of developing venous thromboembolism (VTE). However, clinical studies have yielded variable estimates of this effect. Purpose To perform a meta-analysis designed to evaluate the extent to which statin use influences the rate of subsequent VTE events. Methods We systematically searched MEDLINE, Embase, Web of Science, Cochrane Library and Google Scholar for both randomized controlled trials (RCTs) and observational studies addressing the association between statins and VTE risk, published up until December 1, 2019. Manually reviewed references and key investigators interaction via e-mail correspondence were also data sources. RCTs comparing the effects of statin therapy with those of a placebo or no treatment were included, while interventional studies appraising different lipid-lowering pharmacological strategies were not. Observational studies encompassed both cohort and case-control designs. The primary endpoints were general VTE, deep vein thrombosis or pulmonary embolism. Patients with cancer, heart failure and chronic kidney disease (CKD) were further investigated separately. Study-specific relative risks (RRs) were pooled using generic inverse variance outcome meta-analytic technique with a random-effects model. Results 23 RCTs comprising 118.464 participants, 12 cohort studies encompassing 2.881.184 patients and 9 case-control studies including 354.367 patients were regarded as eligible for quantitative evaluation. Specifically, 5 observational studies comprising 9.656 cancer patients, 3 studies encompassing 9.693 heart failure patients and 4 studies including 4.353 CKD patients were gathered. In RCTs, statin therapy was proven slightly superior to placebo or no treatment in lowering VTE incidence (RR 0.85, 95% CI 0.73–0.99, p=0.04, i2=14%). Observational studies were found to corroborate this effect, with statin treatment resulting in VTE risk reduction overall (RR 0.72, 95% CI 0.64–0.81, p<0.001, i2=84%) and in both cohort (RR 0.86, 95% CI 0.83–0.90, p<0.001, i2=85%) and case-control (RR 0.68, 95% CI 0.57–0.82, p<0.001, i2=80%) designs. This positive effect held true in cancer patients (RR 0.56, 95% CI 0.33–0.95, p=0.03, i2=78%), but not in those with heart failure (RR 0.7, 95% CI 0.42–1.16, p=0.17, i2=2%) and CKD (RR 1.04, 95% CI 0.67–1.60, p=0.87, i2=0%). Conclusion Currently available evidence suggests that statins significantly reduce patients' odds of developing VTE. Given their favorable safety profile and low cost, statin treatment should now be considered in high-risk individuals, particularly in those with cancer. Funding Acknowledgement Type of funding source: None