FSRH CEU Statement: Response to new study by Meaidi et al (2023) Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study

A new study by Meaidi et al. published on 06/09/2023 used data from nationwide Danish databases to compare risk of first VTE events during use of hormonal contraception (HC) with that during concomitant use of HC and the non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen, diclofenac or naproxen.

What do we know already?

The paper cites existing evidence indicating increased risk of arterial thrombotic events and suggesting increased venous thromboembolic (VTE) risk associated with use of non-aspirin NSAIDs (ibuprofen, diclofenac or naproxen) .

Existing evidence, reflected by current clinical guidance, demonstrates increased VTE risk during use of combined hormonal contraceptives; magnitude of risk depends on estrogen dose, progestogen type and route of delivery. There appears to be a lesser increase in VTE risk during use of depot medroxyprogesterone acetate (DMPA), and the evidence indicates that use of progestogen-only pills (POP), the etonogestrel implant (ENG-IMP) and the levonorgestrel-releasing IUD (LNG-IUD) does not increase VTE risk.

What does this study add?

This pharmacoepidemiological analysis contributes data to inform effect on VTE risk of use of non-aspirin NSAIDs alone, hormonal contraceptives alone, and concomitant use of both non-aspirin NSAIDs and hormonal contraceptives.

What conclusions can we draw?

Risk of VTE events amongst women of reproductive age is very small. We already know that VTE risk is increased during use of combined hormonal contraception and (to a lesser extent) DMPA. VTE (and ATE) risk appears to be increased during use of non-aspirin NSAIDs.

This study suggests that when both HC and non-aspirin NSAID are used, VTE risk is higher than with use of either the HC or the non-aspirin NSAID alone, but the numbers of events remain small; the study reports the additional number of VTE events during the first week of prescribed non-aspirin NSAID use at around 4 per 100,000 for non-users of HC, 3 per 100,000 for users of POP, ENG-IMP and LNG-IUD, 11 per 100,000 for users of DMPA or lower risk COCs, and 23 per 100,000 for users of higher risk CHC including the combined patch, ring and COC containing higher risk progestogens.

The study findings are limited by the observational nature of the study design and the potential confounding factors, not least the fact that the reason for prescription of the non-aspirin NSAID could itself affect VTE risk.

Current FSRH guidelines restrict use of HC that has associated increased thrombotic risk by individuals who have additional risk factors for thrombosis, aiming to minimise contraception-associated risk of thrombotic events as much as possible. Thus absolute risk of VTE when non-aspirin NSAIDS are added during use of HC is likely to remain very small.

Clinicians may wish to advise any user of non-aspirin NSAID that the drug could potentially increase VTE risk but this is not currently indicated by product labelling and use of non-aspirin NSAIDs is not restricted on the basis of VTE risk by other significant VTE risk factors like obesity. Much non-aspirin NSAID is bought off the shelf without supervision by a healthcare professional.

It is suggested that when discussing CHC-associated VTE risk, clinicians consider advising users of combined hormonal contraception about potential small additional risk if non-aspirin NSAIDs are used alongside CHC.

The full statement is available below to view and download.