Influence of statin use on the incidence of recurrent venous thromboembolism and major bleeding in patients receiving rivaroxaban or standard anticoagulant therapy

Thrombosis Journal

Anthonie WA Lensing¹  Bruce L Davidson²  Martin H Prins³  Martin Gebel¹  Philip S Wells⁴ 

[1] Bayer HealthCare, Wuppertal, Germany;University of Washington School of Medicine, Seattle, WA, USA;Maastricht University Medical Center, Maastricht, The Netherlands;Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada

关键词: Venous thromboembolism;    Statins;    Rivaroxaban;    Anticoagulant therapy;   

Others  :  1135347
DOI  :  10.1186/1477-9560-12-26

 received in 2014-07-25, accepted in 2014-10-14,  发布年份 2014

【 摘 要 】

Background

Statins may reduce the risk of first and recurrent venous thromboembolism (VTE). No data are available on their potential benefit in patients treated with the oral anticoagulant rivaroxaban.

Methods

The EINSTEIN DVT/PE and EINSTEIN Extension studies compared rivaroxaban with standard of care (n=8280) and placebo (n=1188), respectively. The incidences of recurrent VTE and major bleeding per 100 patient-years for exposure (or not) to statins were calculated. A Cox proportional hazards model was constructed, stratified by index event and intended treatment duration, with statin use as a time-dependent variable, for each treatment group (rivaroxaban vs enoxaparin/vitamin K antagonist or placebo) and adjusted for relevant variables.

Results

In EINSTEIN DVT/PE, 1509 (18.3%) patients used statins during the at-risk period, and 6731 (81.7%) did not. Overall, 2.6 recurrent VTEs occurred per 100 patient-years with statin use compared with 3.8 per 100 patient-years without statins (adjusted hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.46–1.25). HRs for recurrent VTE were similar for concomitant use of rivaroxaban-statin and enoxaparin/VKA-statin. Major bleeding events occurred in 3.0 per 100 patient-years with statin use compared with 2.3 per 100 patient-years without statins (adjusted HR 0.77; 95% CI 0.46–1.29). Due to adjustments in the Cox regression model, the direction of this HR is in contrast to the crude comparison. In EINSTEIN Extension, no recurrent VTEs occurred with statin use in the rivaroxaban group compared with 1.6 per 100 patient-years without statins. In the placebo group, 12.2 recurrent VTEs occurred per 100 patient-years with statin use compared with 13.2 per 100 patient-years without (adjusted HR 0.81; 95% CI 0.35–1.86).

Conclusions

The effect of statins in this secondary analysis of the EINSTEIN VTE treatment program is consistent with other studies that suggest a reduced risk of recurrent VTE, but conclusive evidence of this benefit is lacking. Statins are simple to use, inexpensive, very safe and do not cause bleeding. Therefore, the potential effect on reducing recurrent VTE, which is in the range of that of acetylsalicylic acid, deserves evaluation in a large randomized trial.

Trial registration number

ClinicalTrials.gov: EINSTEIN PE, NCT00439777; EINSTEIN DVT, NCT00440193; EINSTEIN Extension, NCT00439725.

【 授权许可】

   
2014 Wells et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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