Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users.
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).


CONCLUSIONS
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.


METHODS
II.
Cole
J Alexander
JA
i3 Drug Safety, Auburndale, Massachusetts, USA.
Norman
Heather
H
Doherty
Michael
M
Walker
Alexander M
AM
D000279:Administration, Cutaneous; D002545:Brain Ischemia / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D003276:Contraceptives, Oral / Q000008:administration & dosage*; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015994:Incidence; D009203:Myocardial Infarction / Q000453:epidemiology*; D009644:Norgestrel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020521:Stroke / Q000453:epidemiology*; D013923:Thromboembolism / Q000453:epidemiology*; D020246:Venous Thrombosis / Q000453:epidemiology
D003276:Contraceptives, Oral; D004338:Drug Combinations; C511292:Ortho Evra; D009644:Norgestrel; D004997:Ethinyl Estradiol; C017576:norgestimate