title: Impact of estrogen type on cardiovascular safety of combined oral contraceptives.
abstract: The International Active Surveillance study "Safety of Contraceptives: Role of Estrogens" (INAS-SCORE) investigated the cardiovascular risks associated with the use of a combined oral contraceptive (COC) containing dienogest and estradiol valerate (DNG/EV) compared to established COCs in a routine clinical setting.
  
  
  
  Transatlantic, prospective, noninterventional cohort study conducted in the United States and seven European countries with two main exposure groups and one exposure subgroup: new users of DNG/EV and other COC (oCOC), particularly levonorgestrel-containing COCs (LNG). All self-reported clinical outcomes of interest (OoI) were validated via attending physicians and relevant source documents. Main OoI were serious cardiovascular events (SCE), particularly venous thromboembolic (VTEs) events. Comprehensive follow-up procedures were implemented. Statistical analyses were based on Cox regression models.
  
  
  
  A total of 50,203 new COC users were followed up for up to 5.5years (mean value, 2.1years). Overall 20.3% and 79.7% of these women used DNG/EV and oCOC (including 11.5% LNG users), respectively. A low loss to follow-up of 3.1% was achieved. Based on 47 (VTE) and 233 (SCE) events, the primary analysis (European data set) yielded adjusted hazard ratios for DNG/EV vs. oCOC of 0.4 and 0.5, respectively. The upper bounds of the 95% confidence intervals were 0.98 (VTE) and 0.96 (SCE). The corresponding hazard ratios for DNG/EV vs. LNG showed similar point estimates but the confidence intervals included unity.
  
  
  
  DNG/EV is associated with similar or even lower cardiovascular risk compared to oCOC and LNG.
  
  
  
  A COC containing DNG and EV is associated with similar or even lower cardiovascular risk compared to COCs containing levonorgestrel or other progestogens.
authors.affiliation: Pharmacoepidemiology, Berlin, Germany. Electronic address: pharmacoepidemiology@t-online.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Dinger
authors.affiliation: ZEG-Berlin Center for Epidemiology and Health Research, Berlin, Germany.
authors.forename: Thai
authors.initials: T
authors.lastname: Do Minh
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; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects* / Q000737:chemistry; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D016912:Levonorgestrel / Q000009:adverse effects*; D008137:Longitudinal Studies; D009277:Nandrolone / Q000009:adverse effects / Q000031:analogs & derivatives*; D000071066:Patient Reported Outcome Measures; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; C023635:dienogest; D004958:Estradiol; D016912:Levonorgestrel; D009277:Nandrolone
keywords: ATE; Combined oral contraceptives; Dienogest; Estradiol valerate; Routine clinical practice; VTE