(A43) Decreased Venous Thromboembolic Risk of Estradiol Valerate/Dienogest COCs Compared to First-line COCs Containing Ethinyl Estradiol/Levonorgestrel: Pooled Analysis in a Large Real-World User Population
Director of Statistics and Methodology Berlin Center for Epidemiology and Health Research (ZEG) Berlin, Germany
Background: In contrast to ethinyl estradiol (EE), estradiol valerate (E2Val) contained in combined oral contraceptives (COCs) is thought to have less impact on the hepatic system and subsequently improved thrombotic profiles. Previous data from a post-authorization safety study (PASS) have shown a trend towards a reduced risk of venous thromboembolism (VTE) associated with E2Val in combination with dienogest (DNG) compared to COCs containing EE in combination with levonorgestrel (LNG). To further investigate this trend in a large real-world user population, we conducted a pooled analysis of similarly designed large cohort studies investigating cardiovascular safety in users of different COCs.
Objectives: The main objective of this analysis was to compare the VTE risk (i.e., deep venous thrombosis and/or pulmonary embolism) associated with COCs containing E2Val/DNG to those containing EE/LNG in a population that is representative for the actual users of the individual preparations.
Methods: Data regarding users of COCs containing either 3 mg E2Val/3 mg DNG or ≤30 μg EE/LNG were retrieved from the European sub-population of two large prospective, non-interventional, cohort studies. Baseline characteristics, including reproductive, contraceptive and medical history, were summarized using descriptive statistics. Propensity score (PS) sub-classification was applied to balance baseline parameters between cohorts. Time-to-event analysis of VTE events was carried out based on the extended Cox model to calculate crude and adjusted hazard ratios (HR) including 95%-confidence intervals (CI).
Results: The pooled dataset included 11,199 users of E2Val/DNG and 9,666 users of EE/LNG, contributing 17,550 and 17,629 women-years (WY) of observation, respectively. E2Val/DNG users had a higher mean age (31.5 ±9.50 years) than EE/LNG users (25.3 ±8.17 years) but other baseline characteristics were similar between the cohorts. A comparison between cohorts showed a significantly decreased VTE risk in users of COCs containing E2Val/DNG vs users of COCs containing EE/LNG; crude HR: 0.59 (95% CI, 0.28-1.26) and PS-adjusted HR: 0.40 (95% CI, 0.18-0.89).
Conclusions: This pooled analysis supports data from a previous PASS study and confirms a significantly decreased VTE risk of E2Val/DNG COCs compared to EE/LNG COCs. These results provide valuable real-world safety information for clinicians, patients and regulators, by shedding light on the relative safety of current COCs.