Written by Rebecca DiFabio
This Danish nationwide cohort study found that in reproductive-age women, NSAID use alone increased the risk of venous thromboembolism (VTE). The magnitude of risk was compounded by concomitant use of hormonal contraception.
Is it really that risky?
Prior studies have shown increased VTE risk related to NSAID use1,2 and hormonal contraception use, individually.3,4 However, evidence of VTE risk with concomitant use is lacking. This study utilized multiple national Danish health registries to quantify the effects of hormonal contraceptives (sub-categorized as low-, moderate-, and high-risk) and NSAIDs on VTE risk, both in isolation and when taken together.
Compared to the control group, isolated NSAID use resulted in an adjusted incidence rate ratio (IRR) of 7.2 (95%CI 6.0-8.5) for VTE. When taken concurrently with high- and moderate-risk hormonal contraception, this risk was amplified with adjusted IRRs of 44.8 (95%CI 39.2-51.3) and 23.4 (95%CI 17.6-31.1), respectively. Interestingly, when taken with low/no-risk hormonal contraception, the adjusted IRR was less than NSAIDs alone at 4.9 (95%CI 2.8-8.7). That being said, even in the highest risk group (high-risk contraceptive and NSAID use), the absolute risk of VTE was still quite low at 0.02%.
The study was well-designed with a large sample size. Investigators adjusted person-time measurements with temporary or permanent censorship of patients with increased VTE risk (e.g. surgery leading to hospital admission, pregnancy, cancer). Some limitations, such as the assumed start/end dates and duration of NSAID use, and possible confounding by indication are still present, though these seem to be fairly minor concerns, and I feel don’t take away from the strength of the study.
How will this change my practice?
My current practice is to prescribe short courses of the NSAID ibuprofen (which had the smallest IRR of the reported NSAIDs). The absolute risk of VTE in the first week of NSAID use, even in the high-risk hormonal contraception group, was still exceedingly low. This may not change my day-to-day practice; however, the knowledge of these risk factors is important for regular NSAID users and a consideration when selecting contraceptives.
Extra Epi Spoonful
Do the concepts of person-time and rate ratios give you the creeps? Check out this 3-minute video for a quick refresher.
Peer reviewed by Drs. Ketan Patel & Bo Stubblefield
Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study. BMJ 2023; 382 :e074450 doi:10.1136/bmj-2022-074450.
- 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.
- Schmidt M, Christiansen CF, Horvath-Puho E, Glynn RJ, Rothman KJ, Sorensen HT. Non-steroidal anti-inflammatory drug use and risk of venous thromboembolism. Journal of thrombosis and haemostasis : JTH 2011;9:1326-33.
- 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.
- 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.