© ST BARTHOLOMEW'S HOSPITAL/SPL
October 2023
Nationwide study examines VTE risk with combined NSAID and hormonal contraceptive use
By Michael Doris MB BS
Women taking both NSAIDs and certain hormonal contraceptives appear to be at an increased risk of venous thromboembolism (VTE), a large Danish study has found, but Australian experts have stressed the absolute risk is low, even in those using the highest risk hormonal contraceptives.
In a nationwide cohort study, published in the BMJ, researchers examined Danish national registry data on more than two million women aged 15 to 49 years from 1996 and 2017 to examine the effect of concomitant use of hormonal contraception and NSAIDs on VTE risk. The women had no history of venous or arterial thrombotic events, cancer, thrombophilia, hysterectomy, bilateral oophorectomy, sterilisation or infertility treatment.
Hormonal contraception was classified according to pre-established VTE risk. High-risk hormonal contraceptives included combined oestrogen and progestin patches, vaginal rings and tablets containing 50 mcg ethinyloestradiol or specific progestins (desogestrel, gestodene, drospirenone) or the antiandrogen cyproterone. Medium-risk hormonal contraceptives included all other combined oral contraceptive pills and the medroxyprogesterone injection. Low-risk hormonal contraceptives included progestin-only tablets, implants and hormonal intrauterine devices.
Analysed NSAIDs included ibuprofen, diclofenac and naproxen.
During a median follow up of 10 years, representing a combined 21 million person-years, 8710 VTE events occurred.
Compared with non-use of NSAIDs, NSAID use resulted in an adjusted incidence rate ratio of VTE of 7.2 in women not using hormonal contraception, 11.0 in women using high-risk hormonal contraception, 7.9 in women using medium-risk hormonal contraception, and 4.5 in users of low- or no-risk hormonal contraception.
Corresponding numbers of extra VTE events per 100,000 women in the first week of NSAID treatment compared with non-use of NSAIDs were four in women not using hormonal contraception, 23 in women using high-risk hormonal contraception, 11 in those using medium-risk hormonal contraception, and three in users of low- or no-risk hormonal contraception.
The VTE risk was greatest with the use of diclofenac, with a 12-fold increase in events in women not using hormonal contraception. The researchers highlighted this as an area of particular concern.
Commenting on the findings, Dr Clare Boerma, Medical Director of Family Planning Australia, and Dr Kathy McNamee, Medical Director from Sexual Health Victoria, said, ‘this large observational study suggests that additionally using non-aspirin NSAIDs may further increase the VTE risk.’ However, they noted that the absolute risk remained low, even in those using the high-risk hormonal contraceptives.
‘While multiple confounding factors were considered, the study could not fully control for BMI and smoking status, nor over-the-counter NSAID use. Moreover, the reason for the NSAID prescription, rather than the NSAID itself, may have contributed to the risk,’ Drs Boerma and McNamee told Medicine Today.
They advised doctors to continue following current medical eligibility criteria to guide safe contraceptive prescribing, which did not restrict simultaneous NSAID and contraceptive use.
‘However, given the serious nature of VTE, clinicians may choose to advise those on combined hormonal contraceptives regarding the possible small additional VTE risk with use of non-aspirin NSAIDs,’ they said.