Risk of Venous Thromboembolism with Drospirenone in Combined Oral Contraceptive Products

OBJECTIVE: To review primary literature regarding the risk of venous thromboembolism (VTE) in users of combined oral contraceptives (COCs) containing drospirenone compared to COCs containing other progestins. DATA SOURCES: A literature search of MEDLINE and EMBASE (1950-January 2010) was conducted using the following search terms: VTE, thrombosis, thromboembolism, COC, combined hormonal contraceptives, drospirenone, Yasmin, and Yaz. Additional references were retrieved from reference citations. STUDY SELECTION AND DATA EXTRACTION: All English-language primary literature studies were evaluated for relevance. Five studies were identified for evaluation: 1 prescription event monitoring study, 2 prospective postmarketing cohort studies, 1 validation study, and 1 retrospective cohort study. DATA SYNTHESIS: Use of a COC is associated with a 3- to 6-fold increase in VTE risk compared to nonuse. This risk may vary among different oral contraceptives due to the progestin component. Studies evaluated showed that women utilizing a drospirenone-containing COC did not have a higher risk of VTE when compared to women utilizing other progestins. The crude incidence rate ratio for VTE in women taking a COC containing drospirenone compared to a COC containing other progestins ranged from 0.9 to 1.7 (95% CI 0.5 to 2.4). While the studies evaluating VTE risk were mostly large and long term, most failed to consider important risk factors for VTE such as prolonged immobility, obesity, smoking history, and family history of VTE (which could suggest a genetic predisposition to thrombotic events). It was also unclear with some of the studies whether equivalent estrogen doses were used in the comparisons. CONCLUSIONS: Several studies have evaluated the risk of VTE in users of COC-containing drospirenone compared with other progestins, and none were able to show a significantly increased risk of VTE with drospirenone. The recent media attention regarding VTE risk and drospirenone-containing COCs does not seem to be well supported by the research currently available.