Drospirenone and non-fatal venous thromboembolism: is there a risk difference by dosage of ethinyl-estradiol?

Authors

  • S. T. Bird,

    Corresponding author
    1. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Office of Management, CDER Academic Collaboration Program, Silver Spring, MD, USA
    • Pharmaceutical Outcomes and Policy, College of Pharmacy and Epidemiology, University of Florida, Gainesville, FL, USA
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  • J. A. C. Delaney,

    1. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
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  • M. Etminan,

    1. Pharmaceutical Outcomes Programme, University of British Columbia, Vancouver, BC, Canada
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  • J. M. Brophy,

    1. McGill University, Royal Victoria Hospital, Montreal, QC, USA
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  • A. G. Hartzema

    1. Pharmaceutical Outcomes and Policy, College of Pharmacy and Epidemiology, University of Florida, Gainesville, FL, USA
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  • Manuscript Handled by: I. Pabinger Final Decision: F.R. Roseridaal, April 2013

Correspondence: Steven T. Bird, Department of Pharmaceutical Outcomes and Policy, University of Florida, College of Pharmacy, 101 S. Newell Drive (HPNP), PO Box 1 00496, Gainesville, FL 32611, USA.

Tel.: +1 610 506 3869; fax: +1 352 273 6270

E-mail: bird.steven@gmail.com

Summary

Background

Previous studies concluded that there was an increased risk of non-fatal venous thromboembolism (VTE) with drospirenone. It is unknown whether the risk is differential by ethinyl-estradiol dosage.

Objectives

To assess the risk of VTE with drospirenone and to determine whether drospirenone and ethinyl-estradiol 20 μg (DRSP/EE20) has a lower VTE risk than drospirenone and ethinyl-estradiol 30 μg (DRSP/EE30).

Methods

Our cohort included women aged 18–46 years taking drospirenone or levonorgestrel (LNG)-containing combined oral contraceptives (COCs) in the IMS claims database between 2001 and 2009. VTE was defined using ICD-9-CM coding and anticoagulation. The hazard ratio (HR) from Cox proportional hazards models was used to assess the VTE relative risk (RR) with drospirenone compared with levonorgestrel, adjusted by a propensity score used to control for baseline co-morbidity and stratified by EE dosage and user-type (new/current).

Results

The study included 238 683 drospirenone and 193 495 levonorgestrel users. Among new and current users, a 1.90-fold (95% CI, 1.51–2.39) increased VTE relative risk was observed for drospirenone (18.0 VTE/10 000 women-years) vs. levonorgestrel (8.9 VTE/10 000 women-years). In analysis of new users, DRSP/EE20 had a 2.35-fold (95% CI, 1.44–3.82) VTE RR versus LNG/EE20. New users of DRSP/EE30 observed an increased RR versus LNG/EE30 among women starting to use COCs between 2001 and 2006 (2.51, 95% CI, 1.12–5.64) but not between 2007 and 2009 (0.76, 95% CI, 0.42–1.39), attributable to an increased incidence rate with LNG/EE30 from 2007 to 2009. In direct comparison, DRSP/EE20 had an elevated risk of VTE compared with DRSP/EE30 (RR, 1.55; 95% CI, 0.99–2.41).

Conclusions

We observed a modestly elevated risk of VTE with drospirenone, compared with levonorgestrel. The larger VTE incidence rate observed in DRSP/EE20 than in DRSP/EE30 and the increasing VTE incidence rate with levonorgestrel between 2007 and 2009 were unexpected.

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