OBJECTIVE: To estimate the incidence of venous thromboembolism, acute myocardial infarction, and ischemic stroke among transdermal contraceptive system users compared with users of norgestimate-containing oral contraceptives with 35 mcg ethinyl estradiol.
METHODS: We began with insurance claims data from UnitedHealthcare. We identified women exposed to the transdermal contraceptive system or norgestimate-containing oral contraceptives from April 2002 through December 2004. Outcomes were confirmed from medical records. We calculated incidence rates and age-adjusted incidence rate ratios. In a nested case-control analysis, we investigated and controlled for confounding.
RESULTS: There were 49,048 woman-years of transdermal contraceptive system exposure and 202,344 woman-years of norgestimate-containing oral contraceptives exposure. There was a more than two-fold increase in the venous thromboembolism rate (incidence rate ratio 2.2, 95% confidence interval [CI] 1.3–3.8) among transdermal contraceptive system users (20 cases, 40.8 per 100,000 woman-years) compared with norgestimate-containing oral contraceptives users (37 cases, 18.3 per 100,000 woman-years). Acute myocardial infarction occurred in three transdermal contraceptive system users compared with seven among norgestimate-containing oral contraceptives users (incidence rate ratio 1.8, 95% CI 0.5–6.8). No strokes occurred among transdermal contraceptive system users, whereas 10 occurred among norgestimate-containing oral contraceptives users. In the nested case-control analysis, after exclusions for high-risk factors, the odds ratio for venous thromboembolism was 2.4 (95% CI 1.1–5.5).
CONCLUSION: There was a more than two-fold increase in the risk of venous thromboembolism associated with use of the transdermal contraceptive system. Acute myocardial infarction and stroke occurred too rarely to ascertain precise risk estimates.
LEVEL OF EVIDENCE: II
Venous thromboembolism risk with transdermal contraception is increased compared with norgestimate-containing oral contraceptive pills with 35 mcg ethinyl estradiol.
From i3 Drug Safety, Auburndale, Massachusetts.
This research was supported by a research contract between i3 Drug Safety and Johnson & Johnson. The contract granted i3 Drug Safety oversight of the study conduct, report and interpretation, and final wording of any resulting manuscripts.
The authors thank Judy Wong and Sherry Mentor of i3 Drug Safety for their coordination of the medical record abstractions, along with Catherine Johannes, PhD, and Priscilla Velentgas, PhD, formerly of i3 Drug Safety, for their early contributions to the design and conduct of the study.
Corresponding author: Alexander M. Walker, MD, DrPH, 950 Winter Street, Suite 3800, Waltham, MA 02451; e-mail: email@example.com.
Financial Disclosure The authors are salaried employees of i3 and hold stock or stock options in UnitedHealth Group (the parent corporation).