Abstract

Background

Several observational studies in patients at high risk of arterial vascular disease have shown that statin use is associated with a decreased risk of venous thromboembolism (VTE). A recent meta-analysis showed that the odds ratio for a first venous thromboembolic event for statin users was 0.89 (95% confidence interval [CI], 0.78–1.01) compared with non-users (Rahmini K, et al. PLoS Med 2012;9: e1001310 doi:10.1371/journal.pmed.1001310).

Objective

To evaluate the risk of recurrent VTE in patients with VTE treated with an anticoagulant (rivaroxaban or enoxaparin/vitamin K antagonist [VKA]) in relation to the concomitant use of statin therapy in the EINSTEIN-DVT and EINSTEIN-PE studies.

Measurements

Incidence densities of symptomatic recurrent VTE and major bleeding were expressed per 100 patient-years of exposure (or not) to statins. A Cox proportional hazards model was employed, with statin use as a time-dependent variable, for each treatment group (rivaroxaban vs enoxaparin/VKA) and adjusted for aspirin use, age, body mass index, cardiac disorders, gender, and creatinine clearance at baseline.

Results

A total of 1509 (18%) of the 8240 patients included in EINSTEIN-DVT and EINSTEIN-PE used statins during the course of the studies. Statin users were more likely to have cardiovascular disorders (31% vs 10%) and also used aspirin more often (26% vs 5%). During statin/rivaroxaban treatment, recurrent VTE occurred with an incidence of 2.0 per 100 patient-years versus 3.6 during non-statin-use (adjusted hazard ratio [HR], 0.62; 95% CI, 0.29–1.32). During statin/enoxaparin/VKA use, recurrent VTE occurred at an incidence of 3.2 per 100 patient-years versus 4.0 during non-statin-use (adjusted HR, 0.89; 95% CI, 0.47–1.69). Major bleeding during statin/rivaroxaban treatment occurred at an incidence of 2.2 per 100 patient-years versus 1.6 during non-statin-use (adjusted HR, 0.92; 95% CI, 0.43–1.98). During statin/enoxaparin/VKA treatment, the rate of major bleeding was 3.7 per 100 patient-years compared with 3.0 during non-statin-use (adjusted HR, 0.69; 95% CI, 0.36–1.32). Due to the adjustments in the Cox regression model the direction of these hazard ratios are in contrast to the crude comparison of rates by patient-years. This is largely because, in general, statin users are older and most of the major bleeding events in statin users occur in the ≥60 years age group.

Limitations

The study comprised a post-hoc analysis of data collected in two randomized clinical trials. Because the analyses were not a comparison of randomized groups, residual confounding is possible.

Conclusions

A modest, but not statistically significant, reduction in recurrent VTE was observed with statin use in patients treated for VTE. This reduction was similar in patients receiving enoxaparin/VKA or rivaroxaban therapy.

Disclosures:

Gebel:Bayer HealthCare AG: Employment, Equity Ownership. Prins:Bayer HealthCare: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding; sanofi-aventis: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; LeoPharma: Consultancy, Honoraria, Research Funding; ThromboGenics: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Lensing:Bayer HealthCare: Employment.

Author notes

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Asterisk with author names denotes non-ASH members.