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. 2023 Sep 6:382:e074450.
doi: 10.1136/bmj-2022-074450.

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

Amani Meaidi  1   2 , Annamaria Mascolo  3   4 , Maurizio Sessa  5 , Anne Pernille Toft-Petersen  6 , Regitze Skals  7 , Thomas Alexander Gerds  8 , Charlotte Wessel Skovlund  9 , Lina Steinrud Morch  9 , Francesco Rossi  3   4 , Annalisa Capuano  3   4 , Oejvind Lidegaard  1   2 , Christian Torp-Pedersen  8   10   11
Affiliations

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

Amani Meaidi et al. BMJ. .

Abstract

Objective: To study the influence of concomitant use of hormonal contraception and non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of venous thromboembolism.

Design: Nationwide cohort study.

Setting: Denmark through national registries.

Participants: All 15-49 year old women living in Denmark between 1996 and 2017 with no medical history of any venous or arterial thrombotic event, cancer, thrombophilia, hysterectomy, bilateral oophorectomy, sterilisation, or infertility treatment (n=2 029 065).

Main outcome measure: A first time discharge diagnosis of lower limb deep venous thrombosis or pulmonary embolism.

Results: Among 2.0 million women followed for 21.0 million person years, 8710 venous thromboembolic events occurred. Compared with non-use of NSAIDs, use of NSAIDs was associated with an adjusted incidence rate ratio of venous thromboembolism of 7.2 (95% confidence interval 6.0 to 8.5) in women not using hormonal contraception, 11.0 (9.6 to 12.6) in women using high risk hormonal contraception, 7.9 (5.9 to 10.6) in those using medium risk hormonal contraception, and 4.5 (2.6 to 8.1) in users of low/no risk hormonal contraception. The corresponding numbers of extra venous thromboembolic events per 100 000 women over the first week of NSAID treatment compared with non-use of NSAIDs were 4 (3 to 5) in women not using hormonal contraception, 23 (19 to 27) in women using high risk hormonal contraception, 11 (7 to 15) in those using medium risk hormonal contraception, and 3 (0 to 5) in users of low/no risk hormonal contraception.

Conclusions: NSAID use was positively associated with the development of venous thromboembolism in women of reproductive age. The number of extra venous thromboembolic events with NSAID use compared with non-use was significantly larger with concomitant use of high/medium risk hormonal contraception compared with concomitant use of low/no risk hormonal contraception. Women needing both hormonal contraception and regular use of NSAIDs should be advised accordingly.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the Danish Heart Foundation, which funded AM’s salary, including this study; LSM has received grants from the health insurance organisation “Denmark,” the Danish Cancer Society’s Scientific Committee, and Novo Nordisk for research unrelated to the present study; CTP has received grants from Novo Nordisk and Bayer outside the current study; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Flow diagram of formation of study cohort
Fig 2
Fig 2
Adjusted incidence rate ratios of venous thromboembolism and number of extra venous thromboembolic events in non-steroidal anti-inflammatory drug (NSAID) users versus non-users according to use of hormonal contraception. *Incidence rate ratios adjusted for age, calendar time, educational level, hypertension, diabetes, polycystic ovary syndrome, endometriosis, migraine, systemic connective tissue disorders, and inflammatory polyarthropathies. †Standardised incidence rate differences per 100 000 person weeks; standardised according to distribution of age, calendar time, educational level, hypertension, diabetes, polycystic ovary syndrome, endometriosis, migraine, systemic connective tissue disorders, and inflammatory polyarthropathies in entire cohort. CI=confidence interval
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Comment in

References

    1. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2015;350:h2135. 10.1136/bmj.h2135 - DOI - PMC - PubMed
    1. Lidegaard Ø, Nielsen LH, Skovlund CW, Skjeldestad FE, Løkkegaard E. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ 2011;343:d6423. 10.1136/bmj.d6423 - DOI - PMC - PubMed
    1. Ungprasert P, Srivali N, Wijarnpreecha K, Charoenpong P, Knight EL. Non-steroidal anti-inflammatory drugs and risk of venous thromboembolism: a systematic review and meta-analysis. Rheumatology (Oxford) 2015;54:736-42. 10.1093/rheumatology/keu408 - DOI - PubMed
    1. Stegeman BH, de Bastos M, Rosendaal FR, et al. . Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ 2013;347:f5298. 10.1136/bmj.f5298 - DOI - PMC - PubMed
    1. Tchaikovski SN, Rosing J. Mechanisms of estrogen-induced venous thromboembolism. Thromb Res 2010;126:5-11. 10.1016/j.thromres.2010.01.045 - DOI - PubMed

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