title: Cardiovascular and general safety of a 24-day regimen of drospirenone-containing combined oral contraceptives: final results from the International Active Surveillance Study of Women Taking Oral Contraceptives.
abstract: OBJECTIVE
  The "International Active Surveillance Study of Women Taking Oral Contraceptives" investigated the risks of short- and long-term use of an extended 24-day regimen of drospirenone and ethinylestradiol (DRSP24d) compared to established oral contraceptives (OCs) in a routine clinical setting.
  
  
  METHODS
  Prospective, controlled, noninterventional cohort study conducted in the United States and six European countries with three main cohorts: new users of DRSP24d, DRSP21d (21-day regimens of DRSP-containing OCs), and non-DRSP (OCs without DRSP). All self-reported clinical outcomes of interest (OoI) were validated via attending physicians and relevant source documents. Main OoI were serious clinical outcomes, in particular venous thromboembolism (VTE). Comprehensive follow-up procedures were implemented. Statistical analyses were based on Cox regression models. Primary statistical variable was the VTE hazard ratio (HR) for DRSP24d vs. non-DRSP.
  
  
  RESULTS
  A total of 2285 study centers enrolled 85,109 women. Study participants were followed for 2 to 6 years, which generated 206,296 woman-years (WY) of observation. A low loss to follow-up of 3.3% was achieved. DRSP24d, DRSP21d, non-DRSP and levonorgestrel-containing OCs (LNG) showed similar incidence rates of venous and arterial thromboembolism, fatal outcomes, cancer, severe depression and other serious adverse events. VTE incidence rates for DRSP24d, DRSP21d, non-DRSP and LNG were 7.2, 9.4, 9.6 and 9.8 VTE/10,000 WY, respectively. Adjusted HRs for DRSP24d vs. non-DRSP and DRSP24d vs. LNG were 0.8 [95% confidence interval (CI), 0.5-1.3] and 0.8 (95% CI, 0.4-1.5).
  
  
  CONCLUSIONS
  DRSP24d, DRSP21d, non-DRSP and LNG use was associated with similar risks of serious adverse events, and particularly VTE, during routine clinical use.
  
  
  CONCLUSIONS
  The 24-day regimen of drospirenone-containing combined OCs is associated with similar risks of venous and arterial thromboembolism, fatal outcomes, cancer, severe depression and other serious adverse events compared to 21-day regimens of drospirenone-containing combined OCs, OCs without drospirenone and LNGs.
authors.affiliation: ZEG-Berlin Center for Epidemiology and Health Research, Berlin, Germany. Electronic address: dinger@zeg-berlin.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Dinger
authors.affiliation: ZEG-Berlin Center for Epidemiology and Health Research, Berlin, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Bardenheuer
authors.affiliation: ZEG-Berlin Center for Epidemiology and Health Research, Berlin, Germany.
authors.forename: Klaas
authors.initials: K
authors.lastname: Heinemann
mesh_terms: D000328:Adult; D000736:Androstenes / Q000008:administration & dosage / Q000009:adverse effects*; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D011446:Prospective Studies; D054556:Venous Thromboembolism / Q000139:chemically induced*; D055815:Young Adult
chemical_list: D000736:Androstenes; D003277:Contraceptives, Oral, Combined; D000451:Mineralocorticoid Receptor Antagonists; C035144:drospirenone
keywords: ATE; Prospective cohort study; Routine clinical practice; SAE; VTE