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Venous thromboembolism and cardiovascular disease complications in menopausal women using transdermal versus oral estrogen therapy

Simon, James A. MD; Laliberté, François MA; Duh, Mei Sheng MPH, ScD; Pilon, Dominic MA; Kahler, Kristijan H. PhD, RPh; Nyirady, Judit MD, MBA; Davis, Pamela J. MD; Lefebvre, Patrick MA

doi: 10.1097/GME.0000000000000590
Original Articles

Objective: To evaluate the risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) complications, and assess healthcare costs in menopausal women using an estradiol transdermal system versus oral estrogen therapy (ET).

Methods: Health insurance claims from 60 self-insured US companies from 1999 to 2011 were analyzed. Women at least 50 years of age, newly initiated on transdermal or oral ET, were included. Cohorts were matched 1:1 based on exact factors and propensity score-matching methods. The incidence rate ratios (IRRs) of CVD complications, as well as VTE and other CVD events separately, were assessed through conditional Poisson models. Cohorts were also compared for healthcare costs using linear regression models to assess per-patient per-month cost differences. Confidence intervals (CIs) and P values were determined using a nonparametric method for cost outcomes.

Results: From each cohort, 2,551 users were matched to form the study population. A total of 274 transdermal ET users developed CVD complications compared with 316 women in the oral ET cohort (adjusted IRR 0.81; 95% CI, 0.67-0.99). Transdermal ET users also incurred lower adjusted all-cause and VTE/CVD-related healthcare costs relative to oral ET users (all-cause per-patient per-month cost difference [95% CI] = $41 [−34; 137], P = 0.342).

Conclusions: This large matched-cohort study based on real-world data suggests that women receiving transdermal ET have significantly lower incidences of CVD events compared with those receiving oral ET, and that they also incur lower healthcare costs.

1The George Washington University School of Medicine, The Women's Health & Research Consultants, Washington, DC

2Groupe d’analyse, Ltée, Montréal, Quebec, Canada

3Analysis Group, Inc, Boston, MA

4Novartis Pharmaceuticals Corporation, East Hanover, NJ.

Address correspondence to: James A. Simon, MD, Women's Health & Research Consultants, Washington, DC. E-mail:

Received 8 July, 2015

Revised 4 November, 2015

Accepted 4 November, 2015

Funding/support: This research was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ.

Financial disclosure/conflicts of interest: Four of the authors (F.L., M.S.D., D.P., and P.L.) are employees of Analysis Group, Inc, a consulting company that has received research grants from Novartis Pharmaceuticals Corporation. Three of the authors (K.H.K., J.N., and P.J.D.) are employees of Novartis Pharmaceuticals Corporation.

J.A.S. has served (within the past year) or is currently serving as a consultant to or on the advisory boards of AbbVie, Inc (North Chicago, IL), Actavis, PLC (Dublin, Ireland), Amgen Inc (Thousand Oaks, CA), Amneal Pharmaceuticals (Bridgewater, NJ), Apotex, Inc (Toronto, Canada), Ascend Therapeutics (Herndon, VA), Dr. Reddy Laboratories, Ltd (Hyderabad, India), Everett Laboratories, Inc (West Orange, NJ), Lupin Pharmaceuticals (Baltimore, MD), Merck & Co, Inc (Whitehouse Station, NJ), Novartis Pharmaceuticals Corporation (East Hanover, NJ), Noven Pharmaceuticals, Inc (New York, NY), Novo Nordisk (Bagsvrerd, Denmark), Pfizer Inc (New York, NY), Shionogi Inc (Florham Park, NJ), Shippan Point Advisors LLC (Upper Saddle River, NJ), Sprout Pharmaceuticals (Raleigh, NC), TherapeuticsMD (Boca Raton, FL).

In the past year J.A.S. has received or is currently receiving grant/research support from: AbbVie, Inc (North Chicago, IL), Actavis, PLC (Dublin, Ireland), Agile Therapeutics (Princeton, NJ), Bayer Healthcare LLC (Tarrytown, NY), New England Research Institute, Inc (Watertown, MA), Novo Nordisk (Bagsvrerd, Denmark), Palatin Technologies (Cranbury, NJ), and Teva Pharmaceutical Industries Ltd (Jerusalem, Israel), TherapeuticsMD (Boca Raton, FL).

J.A.S. has also served or is currently serving on the speaker's bureaus of: Amgen Inc (Thousand Oaks, CA), Eisai, Inc (Woodcliff Lake, NJ), Merck (Whitehouse Station, NJ), Noven Pharmaceuticals, Inc (New York, NY), Novo Nordisk (Bagsvrerd, Denmark), Shionogi Inc (Florham Park, NJ).

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© 2016 by The North American Menopause Society.