How does VTE risk for the patch and vaginal ring compare with oral contraceptives?

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Clinical Inquiries

How does VTE risk for the patch and vaginal ring compare with oral contraceptives?

J Fam Pract. 2008 October;57(10):680-685

References

1. Abrams LS, Skee D, Natarajan J, Wong FA. Pharmacokinetic overview of Ortho Evra/Evra. Fertil Steril. 2002;77(2 suppl):S3-S12.

2. van den Heuvel MW, van Bragt AJ, Alnabawy AK, Kaptein MC. Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive. Contraception. 2005;72:168-174.

3. US Food and Drug Administration Center for Drug Evaluation and Research. Ortho Evra (norelgestromin/ethinyl estradiol) Information. Available at: www.fda.gov/cder/drug/infopage/orthoevra/default.htm. Accessed July 5, 2008.

4. Cole JA, Norman H, Doherty M, Walker AM. Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users. Obstet Gynecol. 2007;109(2 Pt 1):339-346.

5. Jick SS, Kaye JA, Russmann S, Jick H. Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 mcg of ethinyl estradiol. Contraception. 2006;73:223-228.

6. Jick S, Kaye JA, Li L, Jick H. Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing norgestimate and 35 mcg of ethinyl estradiol. Contraception. 2007;76:4-7.

7. Burkman RT. Transdermal contraceptive patch. In: Rose BD, ed. UpToDate [online database]. Waltham, Mass: UpToDate; 2008.

8. Oddsson K, Leifels-Fischer B, de Melo NR, et al. Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial. Contraception. 2005;71:176-182.

9. Gaffield ME, Curtis KM, Mohllajee AP, Peterson HB. Medical eligibility criteria for new contraceptive methods: combined hormonal patch, combined hormonal vaginal ring and the etonogestrel implant. Contraception. 2006;73:134-144.

10. Reproductive Health and Research World Health Organization. Medical Eligibility Criteria for Contraceptive Use. 3rd ed. Geneva, Switzerland: World Health Organization; 2004. Available at: www.who.int/reproductive-health/publications/mec/mec.pdf. Accessed September 12, 2008.

Another nested case-control study—based on UnitedHealthcare insurance claims data and confirmatory chart reviews—showed contrasting results. The study included 340,377 women between the ages of 15 and 44 years who were new users of the patch or new and previous users of a norgestimate-EE combination OC from April 1, 2002 through December 31, 2004.³ Investigators verified 57 diagnoses of VTE, controlling for confounding factors. The incidence of VTE in this study was 40.8 per 100,000 women-years among patch users and 18.3 per 100,000 women-years among users of the norgestimate-35 μg EE OC. The study reported a more than 2-fold increased risk of VTE in patch users compared to OC users (OR=2.4; 95% CI, 1.1-5.5; IRR=2.2; 95% CI, 1.3-3.8).^3,7

FAST TRACK

The patient’s preference should determine the choice between an estrogen-containing OC and the patch or ring

Do the differences between studies make a difference?

The 2 studies appear similar in design but have 2 major identifiable differences:

The first study verified VTE diagnoses by claims for systemic anticoagulants, whereas the second study expanded its analysis by performing confirmatory chart reviews for VTE diagnoses.
The first study included only new OC and patch users as of April 1, 2002, whereas the second study included new and experienced users of the OC as of April 1, 2002.

The significance of the differences in these studies is debatable; the results have yielded controversial, conflicting evidence.

Safety and tolerability are similar for the vaginal ring and OCs

A 1-year, open-label, randomized Phase III study of 1030 women compared the NuvaRing with a combination OC containing levonorgestrel and 30 μg EE. One case of deep venous thrombosis occurred in the NuvaRing group.

In reviewing the data, the authors concluded that the NuvaRing demonstrated comparable safety and tolerability to the OC.⁸ NuvaRing users experienced similar side effects compared with OC users.⁹

Recommendations

The World Health Organization Medical Eligibility Criteria for Contraceptive Use (WHOMEC) reports that long-term safety data for the estrogen-progestin contraceptive patch are not available.¹⁰ However, the limited studies that are available suggest a safety profile similar to that of combination OCs with comparable hormone formulations.

WHOMEC suggests that the guidelines for combination OCs also should apply to the patch and the ring. Women shouldn’t use these contraceptive methods if they have a history of VTE or current VTE or if they are undergoing major surgery that may include prolonged immobilization.¹⁰

Evidence-based answers from the Family Physicians Inquiries Network

How does VTE risk for the patch and vaginal ring compare with oral contraceptives?

References

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