Statin use and venous thromboembolism recurrence: a combined nationwide cohort and nested case-control study

Background: Data on statins' effect on venous thromboembolism (VTE) recurrence are conflicting. Objectives: We examined whether statin use was associated with reduced risk of recurrent VTE in a nationwide population-based setting. Patients/Methods: Using the Danish National Patient Registry, we identified first-time and recurrent VTEs between 1 July 2004 and 31 December 2012 (n = 27 862). VTE diagnoses were validated by medical record review of a subsample of patients. We ascertained nationwide prescription data and categorized statin use as current (further divided into new and long-term use), former and no use. We identified statin use at baseline (mimicking an intention-to-treat analysis) and in a time-varying manner during follow-up (mimicking perprotocol analysis) and computed hazard ratios (HRs) for recurrent VTE using Cox regression. In a supplementary nested case-control study, we identified statin use at time of VTE recurrence and computed odds ratios as unbiased estimates of the incidence rate ratios (IRRs) using conditional logistic regression. We adjusted for age, sex, year of diagnosis, provoking factors, co-morbidities and co-medications, including time-varying use of aspirin and anticoagulant drugs. Results: The adjusted HR comparing current use with no use was 0.72 (95% confidence interval [CI], 0.59-0.88) for recurrent VTE, with a stronger effect of high (0.40; 95% CI, 0.21-0.78) vs. low potency statins (0.77; 95% CI, 0.63-0.94). Consistently, the recurrence rate was reduced in both the time-varying analysis (HR=0.64; 95% CI, 0.54-0.77) and nested case-control analysis (IRR=0.55; 95% CI, 0.45-0.67). The effect was largest for recurrent deep venous thrombosis. Conclusions: Statin use was associated with reduced VTE recurrence.