BACKGROUND AND PURPOSE:

• The use of hormonal contraception and NSAIDs are individual risk factors for venous thromboembolism (VTE)
• Meaidi et al. (BMJ, 2023) assess the incidence of VTE in women using hormonal contraception and NSAIDs simultaneously

METHODS:

• Nationwide cohort study
  • National Danish registry | Personal ID numbers
• Population
  • All 15 to 49-year-old women living in Denmark between 1996 and 2017
  • Exclusion: Venous or arterial thrombotic event | Cancer | Thrombophilia | Hysterectomy | Bilateral oophorectomy | Sterilization | Infertility
• Exposures
  • Concurrent use of hormonal contraception and NSAIDs
  • Examples of NSAIDs include ibuprofen, diclofenac, and naproxen
• Study design
  • High-risk hormonal contraceptives
    • Combined estrogen and progestin patch
    • Vaginal ring
    • Tablets:  50 µg ethinyl estradiol | Progestins (desogestrel, gestodene, drospirenone) | Anti-androgen: cyproterone
  • Medium-risk hormonal contraception
    • All other combined oral contraceptives
    • Medroxyprogesterone injection
  • Low/no risk hormonal contraceptives
    • Progestin-only tablets
    • Implants
    • Hormonal IUDs
• Primary outcome
  • A first-time discharge diagnosis of lower limb deep venous thrombosis or pulmonary embolism

RESULTS:

• 2.0 million women | 21.0 million person-years of follow-up
  • VTE events: 8710
• Compared with non-use of NSAIDs, use of NSAIDs was associated with a higher adjusted incidence rate ratio (aIRR) of VTE in women
  • Not using hormonal contraception
    • aIRR 7.2 (95% CI, 6.0 to 8.5)
  • Using high risk hormonal contraception
    • aIRR 11.0 (95% CI, 9.6 to 12.6)
  • Using medium risk hormonal contraception
    • aIRR 7.9 (95% CI, 5.9 to 10.6)
  • Using low/no risk hormonal contraception
    • aIRR 4.5 (95% CI, 2.6 to 8.1)
• Number of extra VTE events over the first week of NSAID treatment compared with non-use of NSAIDs
  • Not using hormonal contraception
    • 4 (95% CI, 3 to 5) per 100,000 women
  • Using high risk hormonal contraception
    • 23 (95% CI, 19 to 27) per 100,000 women
  • Using medium risk hormonal contraception
    • 11 (95% CI, 7 to 15) per 100,000 women
  • Using low/no risk hormonal contraception
    • 3 (95% CI, 0 to 5) per 100,000 women

CONCLUSION:

• Reproductive-age women who used NSAIDs were more likely to develop VTE than non-users
• The number of VTE events was significantly higher in women using NSAIDs with high/moderate risk hormonal contraception vs low-risk contraception or no hormonal contraception use
• The authors state

Despite the high incidence rate ratios, the absolute risk of venous thromboembolic event in the first week after NSAID purchase remained low even in users of high risk hormonal contraception (0.02%)

• A related editorial states

Among individual NSAIDs, the association was strongest for the older COX-2 inhibitor diclofenac (12-fold increased risk in women not using hormonal contraception)

These data add to existing evidence and concerns about the cardiovascular safety of diclofenac

Learn More – Primary Sources:

Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study

Editorial: NSAIDs, hormonal contraception, and venous thromboembolism