New research finds that women who use NSAIDs and hormonal contraceptives are at increased risk of blood clots, especially the high-risk types and diclofenac. The study calls for increased awareness and careful consideration of safer pain relief and contraceptive methods. The researchers suggest that although the absolute risk remains low, women should be informed accordingly.

People who take hormonal contraceptives along with nonsteroidal anti-inflammatory pain relievers may face a slightly higher risk of venous thromboembolism (VTE), according to a comprehensive Danish study recently published in The BMJ.

The risk is greater for women who use combined oral contraceptives containing third- or fourth-generation progestins, but less for women who use progestin-only tablets, implants, and rings as well as the nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen, diclofenac, and naproxen.

The researchers emphasize that the absolute risk of serious blood clots is low, even among women using high-risk hormonal contraceptives. But given the widespread use of hormonal contraceptives and NSAIDs, they believe women should be informed of this potential drug interaction.

NSAIDs have been previously associated with blood clots, but little is known about whether NSAID use affects the risk of venous thromboembolism in healthy women using hormonal contraceptives.

To address this question, researchers used national medical records to track first-time VTE diagnoses among 2 million women aged 15 to 49 living in Denmark between 1996 and 2017 with no history of blood clots, cancer, hysterectomies or fertility treatments.

Based on the results of previous studies, the relationship between hormonal contraception and VTE is divided into high risk, moderate risk, and low risk.

High-risk hormonal contraceptives include combined estrogen and progestin patches, vaginal rings, and pills containing 50 mcg of estrogen or third- or fourth-generation progestins. Moderate-risk birth control pills include all other combined oral contraceptive pills and medroxyprogesterone injection, while progestin-only pills, implants, and hormonal intrauterine devices (IUDs) are classified as low or no risk.

The study also took into account a range of potentially influencing factors, such as age, education, pregnancy, previous surgery, high blood pressure and diabetes.

In the study, 529,704 women used NSAIDs while using hormonal contraceptives. Ibuprofen was the most commonly used NSAID (60%), followed by diclofenac (20%) and naproxen (6%).

During an average surveillance period of 10 years, a total of 8710 VTE events occurred (2715 pulmonary embolism and 5995 deep vein thrombosis), and 228 women (2.6%) died within 30 days of diagnosis.

In absolute terms, four more VTE events per week occurred among women who were not using hormonal contraception, 11 more among women who used moderate-risk hormonal contraception, and 23 more among women who used high-risk hormonal contraception.

Of the various NSAIDs, diclofenac is most strongly associated with ibuprofen and naproxen.

This was an observational study, so the cause could not be determined, and the researchers highlighted some limitations, such as a lack of information on smoking and obesity, which they said could have affected the findings.

However, this was a large study based on high-quality registry data, and the researchers were able to adjust for a variety of potential influencing factors. What's more, these associations persisted after further analysis, suggesting they are robust.

Therefore, the researchers concluded, "This nationwide study, using a high-quality, linkable national register, provides new knowledge about the risk of potentially fatal events during concurrent use of two medications that are frequently prescribed to healthy women. Women who require concurrent use of hormonal contraceptives and regular NSAIDs should be counseled accordingly."

Morten Schmidt of Aarhus University Hospital wrote in a related editorial that these data raise serious concerns about the concurrent use of NSAIDs (especially diclofenac) and high-risk hormonal contraceptives.

He recommended that medical and regulatory agencies should include these findings in their safety assessments of over-the-counter diclofenac, and that women using hormonal contraceptives and their clinicians should consider using medications other than NSAIDs for pain relief.

"If treatment with NSAIDs is necessary, drugs other than diclofenac appear to be preferable, along with lower-risk hormonal contraceptives such as progestin-only pills, implants, or intrauterine devices," he concluded.

This research was funded by the Danish Heart Foundation.

Compiled source: ScitechDaily