Drospirenone plus estradiol and the risk of serious cardiovascular events in postmenopausal women.

OBJECTIVES

To compare incidence rates of serious cardiovascular events, particularly arterial thromboembolic events (ATE), in users of hormone replacement therapy (HRT), particularly oral continuous combined preparations.

METHODS

Prospective, controlled cohort study with four arms: women using (1) drospirenone (DRSP)/estradiol, (2) other oral continuous combined HRT (HRTcc), (3) all other oral HRTs, and (4) non-oral HRT. The study population consisted of women aged 40+ years in seven European countries who were new users of HRT at the time of inclusion. All patient-reported outcomes of interest were validated by the treating physicians. A multifaceted, four-level follow-up procedure ensured low loss to follow-up rates. The final analysis is based on Cox regression models comparing the cohorts.

RESULTS

In total, 30 597 women were recruited by 1052 study centers. Follow-up reflects 101 715 woman-years of observation. Loss to follow-up was about 2.8%. Risk estimates for general serious adverse events were similar for all cohorts. Incidence rates for serious cardiovascular events were 98.4 (DRSP/estradiol) and 169.7 (HRTcc) per 10 000 woman-years. The corresponding incidence rates for ATE were 10.9 and 29.7 events per 10 000 woman-years with an adjusted hazard ratio of 0.5 (95% confidence interval 0.3-0.8). The initiation rate for antihypertensive treatment after start of HRT was substantially lower for women using DRSP/estradiol compared to the other cohorts.

CONCLUSIONS

DRSP/estradiol is associated with general health risks similar to other oral and non-oral HRT but is probably associated with lower ATE risk.

CLINICAL TRIAL REGISTRATION: NCT00214903, US National Library of Medicine.