- Medicines and Healthcare products Regulatory Agency
- 26 June 2015
- Therapeutic area:
- Cardiovascular disease and lipidology, Obstetrics, gynaecology and fertility, Pain management and palliation, and Rheumatology
EU review confirms that the cardiovascular risk of high-dose ibuprofen (≥2400mg/day) is similar to COX 2 inhibitors and diclofenac.
When prescribing or dispensing ibuprofen:
- avoid use of high-dose ibuprofen (≥2400 mg per day) in patients with established:
- ischaemic heart disease
- peripheral arterial disease
- cerebrovascular disease
- congestive heart failure (New York Heart Association [NYHA] classification II-III)
- uncontrolled hypertension
- review the treatment of patients with the above conditions who are taking high-dose ibuprofen at their next routine appointment
- carefully consider the benefits and risks before starting long-term ibuprofen treatment for patients with significant risk factors for cardiovascular events (eg hypertension, hyperlipidaemia, diabetes mellitus, smoking), particularly if high doses are required
- we remind you that ibuprofen is contraindicated in patients with severe heart failure
- consider that these recommendations also apply to dexibuprofen (a high dose of dexibuprofen is 1200 mg or more per day, which is equivalent to 2400 mg of ibuprofen)
- consider that no increase in cardiovascular risk is seen with ibuprofen at doses up to 1200 mg per day (the highest dose available over the counter) compared with not taking ibuprofen
Ibuprofen is a non-selective anti-inflammatory drug (NSAID). NSAIDs have long been known to be associated with a small increase in risk of heart attack and stroke.
High-dose ibuprofen and cardiovascular risks
MHRA and other EU medicines regulators have reviewed the safety of high-dose ibuprofen, following the publication of a meta-analysis of clinical trial data.1 This meta-analysis showed that people taking ≥2400 mg of ibuprofen per day are at a higher risk of arterial thrombotic events (heart attack, stroke) than people taking placebo. The review confirmed that this higher risk is similar to that seen with COX-2 inhibitors and diclofenac.
No increased risk of arterial thrombotic events is seen with ibuprofen at doses up to 1200 mg per day (the highest dose available over the counter) compared with not taking ibuprofen. There are limited data on the risk with ibuprofen at doses between 1200 mg and 2400 mg per day. It is uncertain whether such doses are associated with an increased cardiovascular risk compared with not taking ibuprofen.
In 2013, less than 1% of all prescriptions for ibuprofen in primary care in the UK were for 2400 mg per day or more.
Possible interaction between ibuprofen and low-dose aspirin
The European review also considered the latest data on the possible interaction between ibuprofen and low-dose aspirin. The latest experimental data confirm previous findings that ibuprofen competitively inhibits the effect of low-dose aspirin on platelet aggregation in vivo, ex vivo and in vitro. It is uncertain if these data can be extrapolated to the clinical situation, and clinical data do not support a clinically meaningful interaction. However, the possibility that long-term, daily use of ibuprofen might reduce the cardioprotective effects of low-dose aspirin cannot be excluded.
Occasional ibuprofen use is unlikely to have a clinically meaningful effect on the benefits of low-dose aspirin.
Reminder of existing advice for all NSAIDs
When prescribing any NSAID, we remind you:
- to base the decision to prescribe an NSAID on an assessment of a patient’s individual risk factors, including any history of cardiovascular and gastrointestinal illness
- that naproxen and low-dose ibuprofen (≤1200 mg per day) are considered to have the most favourable thrombotic cardiovascular safety profiles of all NSAIDs
- to use the lowest effective dose for the shortest duration necessary to control symptoms and re-evaluate the patient’s need for symptomatic relief and response to treatment periodically
Article citation: Drug Safety Update Volume 8 issue 11 June 2015 2.
Coxib and traditional NSAID Trialists’ (CNT) Collaboration. ‘Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials’ Lancet 2013: volume 382, pages 769–779 (viewed on 25 June 2015) ↩
Published: 26 June 2015