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.