Scientific Publications by FDA Staff

J Thromb Haemost 2013 Jun;11(6):1059-68

Drospirenone and non-fatal venous thromboembolism: Is there a risk difference by dosage of Ethinyl-Estradiol?

Bird ST, Delaney JA, Etminan M, Brophy JM, Hartzema AG

BACKGROUND: Previous studies concluded increased risk for non-fatal venous thromboembolism (VTE) with drospirenone. It is unknown whether risk is differential by ethinyl-estradiol dosage. OBJECTIVES: To assess VTE risk with drospirenone and to determine whether drospirenone and ethinyl-estradiol 20mug (DRSP/EE20) has a lower VTE risk than drospirenone and ethinyl-estradiol 30mug (DRSP/EE30). METHODS: Our cohort included women aged 18-46 years taking drospirenone or levonorgestrel (LNG)-containing combined oral contraceptives (COC) in the IMS claims-database between 2001-2009. VTE was defined using ICD-9-CM coding and anticoagulation. The hazard ratio (HR) from Cox Proportional Hazards Models was used to assess the VTE relative risk (RR) with drospirenone compared to levonorgestrel, adjusted by a propensity score used to control for baseline comorbidity and stratified by EE dosage and user-type (new/prevalent). RESULTS: The study included 238,683 drospirenone and 193,495 levonorgestrel users. Among new and prevalent-users, a 1.90-fold (95%CI: 1.51-2.39) increased VTE relative risk was observed for drospirenone (18.0 VTE/10,000 women-years) versus levonorgestrel (8.9 VTE/10,000 women-years). In analysis of new-users, DRSP/EE20 had a 2.35-fold (95%CI: 1.44-3.82) VTE RR versus LNG/EE20. DRSP/EE30 new-users observed an increased RR versus LNG/EE30 among women initiating COCs between 2001-2006 (2.51 95%CI: 1.12-5.64) but not 2007-2009 (0.76 95%CI: 0.42-1.39), attributable to an increased incidence-rate with LNG/EE30 from 2007-2009. In direct comparison, DRSP/EE20 had elevated VTE risk compared to DRSP/EE30 [RR 1.55 (95%CI: 0.99-2.41). CONCLUSIONS: We observed modestly elevated VTE risk with drospirenone, compared to levonorgestrel. The larger VTE incidence-rate observed in DRSP/EE20 than DRSP/EE30, and the increasing VTE incidence-rate with levonorgestrel between 2007-2009 were unexpected.