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Clinical Question
Is the risk of venous thromboembolism increased when a nonsteroidal anti-inflammatory drug is taken with a hormonal contraceptive?
Bottom line
In this large study of women, NSAID use was associated with a small increase (0.004%) in the risk of VTE. Combining NSAID use with a medium-risk hormonal contraceptive increases the risk to 0.011%; the addition of a high-risk hormonal contraceptive increases the risk to 0.023%. 1b
Reference
Study design: Cohort (prospective)
Funding: Foundation
Setting: Population-based
Synopsis
This study used the national registry of Denmark to identify all women aged 15 to 49 years without a history of a venous thromboembolism (VTE) or thrombophilia who were eligible to receive oral contraception. The registry allows careful follow-up of all women. The 2,029,065 women were monitored for oral contraceptive use, nonsteroidal anti-inflammatory drug (NSAID) use, and the development of a VTE, which occurred in 8710 women, over a median of 10 years. Contraceptive methods were categorized by their inherent risk of VTE. High-risk contraceptives include combined estrogen/progestin patch; vaginal ring; tablets containing 50 mcg ethinyl estradiol; tablets containing the progestins desogestrel, gestodene, and drospirenone; and tablets containing the anti-androgen cyproterone. Progestin-only contraception, with the exception of medroxyprogesterone injection, and hormone intrauterine devices were considered low risk, and every other contraceptive option was considered medium risk. VTE was associated with use of an NSAID in women who were not taking hormonal contraception (adjusted rate ratio 7.2; 95% CI 6.0 - 8.5) and the risk was higher in women who were also taking high-risk hormonal contraception (adjusted risk ratio 11.0; 9.6 - 12.6). VTE risk was slightly higher with a medium-risk contraceptive and an NSAID than with NSAID alone (7.9; 5.9 - 10.6). The rates of VTE are still very low; there will be 4 additional episodes of VTE in 100,000 women in the first week of NSAID use, which jumps to 11 in women using medium-risk hormonal contraception and 23 in women using high-risk hormonal contraception.
Reviewer
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA
Comments
Impact assessment
Excellent
CERTAIN CONTRACEPTIVES INCREASE THROMBOEMBOLIC RISKS WITH
GOOD TO KNOW