Drospirenone Increases Venous and Arterial Blockage Risks

Women who use oral contraceptives that contain drospirenone may be at increased risk of developing arterial blockages and blood clots compared with women who use conventional combined hormonal contraceptives, according to results from a retrospective study that included more than a half million new users of contraceptives. The study was published online October 22 in Contraception.

"It is well known that the use of combined hormonal contraceptives (CHCs) is associated with an increased risk of venous thromboembolic events (VTEs), including deep vein thrombosis...and pulmonary embolism...and may be associated with an increased risk of the arterial thromboembolic events (ATEs), including acute myocardial infarction...and ischemic stroke," write the authors, lead by Stephen Sidney, MD, MPH, director of Research Clinics at the Kaiser Permanente Northern California Division of Research in Oakland.

They note that during the last decade, 3 new CHCs have been approved by the US Food and Drug Administration: drospirenone/ethinyl estradiol pills (DRSPs), the norelgestromin/ethinyl estradiol transdermal patch (NGMN), and the etonogestrel/ethinyl estradiol vaginal ring (ETON).

Since these new birth control methods were introduced, several studies have been carried out to discover whether they carry any additional risk for arterial blockages or blood clots compared with low-dose CHCs. The results of these studies, however, have been inconsistent.

The authors of the current study say it is unclear whether the inconsistencies in the findings were the result of differences in the way the studies were carried out or were a result of differences in the populations studied.

"Thus, there is a great deal of concern and confusion among women and their health care providers regarding the safety of these newer preparations relative to older CHCs," the authors write.

Aiming to eliminate at least some of that confusion, these investigators used a different design, focusing on only new users of CHCs, to assess risks associated with the newer CHCs relative to low-dose estrogen CHCs.

The study group included 573,680 new users of CHCs from 4 geographically and demographically diverse health groups: Kaiser-Permanente Northern California, Kaiser-Permanente Southern California, Tennessee State Medicaid, and Washington State Medicaid. The study population ranged in age from 10 to 55 years, with a mean 26.4 years. Each of the women had started taking either a DRSP-containing CHC or 1 of 4 low-dose estrogen CHCs during the period between 2001 and 2007.

The 4 low-dose CHCs included in the study were levonorgestrel (0.10 mg)/ethinyl estradiol (20 μg) tablets, levonorgestrel (0.15 mg)/ethinyl estradiol (30 μg) tablets, norethindrone (1 mg)/ethinyl estradiol (20 μg) tablets, and norgestimate (0.18 - 0.25 mg)/ethinyl estradiol (35 μg) tablets.

The researchers checked for associations between use of the various types of contraceptives and incidence of arterial blockages and blood clots, using Cox proportional hazards regression models to adjust for age, site, and year of entry into the study.

They report that among this cohort of new users, women who took a DRSP-containing CHC were 77% more likely to be hospitalized for VTE. Taking DRSP-containing contraceptives also doubled their risk for ATE compared with women who took low-dose estrogen CHCs.

"The hazards ratio for DRSP in relation to low-dose estrogen comparators among new users was 1.77 (95% confidence interval 1.33–2.35) for VTE and 2.01 (1.06–3.81) for ATE," the researchers write. Further, they note, "The increased risk of DRSP was limited to the 10–34-year age group for VTE and the 35–55-year group for ATE."

The authors found no such increased risk among women who had used the NGMN patch or the ETON vaginal ring.

One study limitation was that the assessment of CHC exposure periods was based on electronic pharmacy records of filled prescriptions rather than information on actual intake.

"Though the absolute incidence of VTE is low," the researchers conclude, "the growing number of studies showing an increased risk of VTE with DRSP suggests that DRSP-containing CHCs should be used cautiously for women seeking hormonal contraception."

Funding for the study was provided by the US Food and Drug Administration, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research. The authors have disclosed no relevant financial relationships.

Contraception. Published online October 22, 2012. Abstract