Is a transdermal patch more likely to cause VTE than an OC?

Key Points

On November 10, 2005, the FDA issued a press release stating that Ortho Evra, a transdermal contraceptive patch, exposes women to a greater amount of estrogen over time.¹ Subsequently, the patch labeling was updated to include a warning about this higher exposure.

Here are the facts:

1. The contraceptive patch delivers daily 20 μg of ethinyl estradiol and 150 mg of norelgestromin (the primary active metabolite of orally administered norgestimate).

3. Peak estrogen blood levels with the patch are about 25% to 35% lower compared with oral products containing 30 μg or 35 μg ethinyl estradiol.^4,5

4. Over time, patch users are exposed to about 60% more estrogen compared with an oral product containing 35 μg of ethinyl estradiol.

Which is more important, a higher peak level or greater exposure over time? Or maybe it doesn't make a difference. The first concern-that there might be an increased risk of venous thromboembolism (VTE) with the patch-came from reports in the media based on anecdotal reports provided to the FDA (a numerator without a denominator). Johnson & Johnson, the parent company for the Evra patch, provided research funds for two epidemiologic studies.

Taking a closer look at the two studies

JICK AND COLLEAGUES, epidemiologists at Boston University School of Medicine, performed a case–control study of nonfatal venous thrombosis using information derived from a very large United States database that records prescriptions and diagnoses longitudinally in managed health-care plans.⁶ Over a 3-year period, the researchers compared new patch users with new users of an OC containing 35 μg ethinyl estradiol and norgestimate. There was a total of 68 cases of venous thrombosis, with 266 controls identified and matched for year of birth and for the date of the thrombotic episode (thus providing comparable dates for exposure). Among women on the patch, there were 31 cases of VTE, with 127 women serving as controls. The bottom line: When the two methods were compared, there was no difference in the risk of VTE (OR=0.9; 95% CI, 0.5–1.6).⁶

One of the strengths of this report is that only new users were studied, eliminating the problem known as attrition of susceptibles (comparing new users to old users would be comparing two different groups of subjects).⁶ Documentation was another strength of this study: The VTE diagnosis was so certain that all affected patients received anticoagulants.

Adjusting for age, duration of exposure, hospitalization or non-hospitalization, and frequency of health-care visits did not change the result: The risk for nonfatal venous thrombosis was similar in new users of the patch compared with new users of OCs.⁶ An analysis for myocardial infarction and stroke risks in the database will be reported in the future.

Jick and associates extended their study with an additional 17 months of data that produced 56 cases of newly diagnosed, idiopathic VTE.⁷ Again, no difference was found comparing users of the transdermal patch with users of an oral contraceptive containing 35 μg ethinyl estradiol and norgestimate (OR=1.1; 95% CI, 0.6–2.1). Combining the cases and controls in the two reports yielded 124 cases and 478 controls (OR=1.0; 95% CI, 0.7–1.5).