Statin Use and Risk Of Recurrent Venous Thrombosis: Results From The MEGA Follow-Up Study
Authors: Lijfering Willem , Braekkan Sigrid , Caram-Deelder Camila , Rosendaal Frits R. , Cannegieter Suzanne C. 
Published: October 2019

Abstract

Introduction
Results from randomized trials have indicated that statins may protect against a first venous thrombosis. Whether initiation of statin use after a first venous thrombosis reduces the risk of recurrence is uncertain. No randomized trial exists, and the few observational studies that have been conducted included both incident and prevalent statin users which may have led to overestimation of results due to a ‘healthy user effect’. Therefore, the aim of this study was to examine the risk of recurrent venous thrombosis in incident statin users versus non-users.

Methods
We used data from the MEGA follow-up study. Patients with a first venous thrombosis (n=4731) were recruited in the period 1999-2004 and followed for an average of 5.2 years. Information on statin use was obtained by linkage to the Dutch Foundation for Pharmaceutical Statistics (SFK) registry. The SFK gathers its data from a panel of non-hospital based pharmacies; more than 95 % of the community pharmacies in the Netherlands are represented on this panel. Linkage was based on a combination of age, sex, 4-digit postal code and vitamin K antagonist use within the first month after the initial venous thrombosis. Cox proportional hazard regression models with statin exposure as a time-dependent variable were used to estimate hazard ratios (HR) with 95% confidence intervals (CI95) for risk of recurrent venous thrombosis. Adjustments were conducted using two different approaches: a multivariable model that included age, sex, body mass index and smoking, and a propensity score model that was based on age (>50 years), sex, characteristics of the first event (provoked/unprovoked) and factor V Leiden.

Results
In total, 2547 (53.2%) MEGA patients with a first venous thrombosis were uniquely linked to the SFK registry. Baseline characteristics did not differ between those who were and were not linked, which indicates low chance of selection bias in the linkage process. Prevalent statin users at baseline (n=153) were excluded from all analyses. During a total of 12844 person-years of follow-up, statin therapy was initiated in 233 (9.3%) patients. There were 347 definite recurrent venous thrombotic events, of which 16 occurred among statin users. Incident statin use was associated with 24% lower risk of recurrence (HR 0.76, CI95: 0.46-1.26) after adjustments for age and sex; with 17% lower risk after adjustments for age, sex, body mass index and smoking (HR 0.83, CI95: 0.52-1.31); and 15% lower risk when propensity score were taken into account (HR 0.85, CI95: 0.50-1.43). Statin use did not have any effect on recurrence in patients with an unprovoked first event (HR 1.04, CI95: 0.54-1.98), whereas a 37% lower risk was found in those with a provoked first event (HR 0.63 CI95: 0.26-1.53) after adjustment for propensity score.

Conclusion
Our findings imply that statins have only a modest effect on risk of recurrent venous thrombosis. Furthermore, we found no association between statin use and risk of recurrence in those with an unprovoked first event, which indicates that statins are likely to play only a minor role in secondary prevention of venous thrombosis.

Disclosures:
Off Label Use: Drug=statin Off-label use= whether or not statins prevent recurrent venous thrombosis.