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Evidence in brief

New evidence on risks associated with NSAIDs


New evidence from randomised controlled trials on cardiovascular and gastrointestinal risks of non-steroidal anti-inflammatory drugs reinforces the need to review all patients taking such medication

An increased risk of heart attack and stroke with some non-selective non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, is well recognised, particularly with long-term use of high doses and in patients who are already at a high risk.

The Medicines and Healthcare products Regulatory Agency (MHRA) has summarised the cardiovascular safety of COX-2 inhibitors and non-selective NSAIDs.

Current advice

The MHRA has advised that systemic diclofenac is now contraindicated in people with established ischaemic heart disease, peripheral arterial disease, cerebrovascular disease or congestive heart failure ( Patients with these conditions should be switched to an alternative treatment at their next routine appointment.

Diclofenac treatment should be initiated only after careful consideration in people with significant risk factors for cardiovascular events, for example hypertension, hyperlipidaemia, diabetes mellitus, or smoking.

The new advice applies to all systemic formulations including those available over the counter in pharmacies; it does not apply to topical formulations.

New evidence

A meta-analysis by the Coxib and traditional NSAID Trialists’ Collaboration (2013) aimed to quantify the cardiovascular and gastrointestinal risks of NSAIDs using data from randomised controlled trials. It included 280 trials of an NSAID compared with placebo and 474 trials of an NSAID compared with another NSAID.

The primary outcomes were major vascular events and upper gastrointestinal complications.

Compared with placebo, major vascular events were significantly increased by more than one third for COX-2 inhibitors and diclofenac 150mg daily. This was mainly due to an increase in major coronary events. The absolute increase in risk was small but serious; compared with placebo, COX-2 inhibitors or diclofenac 150mg daily caused around three additional major vascular events per 1,000 participants per year, one of which was fatal.

Ibuprofen 2,400mg daily did not significantly increase the risk of major vascular events compared with placebo; however, it doubled the risk of major coronary events. Naproxen 1,000mg daily did not significantly increase major vascular or coronary events compared with placebo. The proportional cardiovascular and gastrointestinal risks of all NSAIDs appeared independent of baseline characteristics, including vascular risk.

The risk of hospitalisation due to heart failure was approximately doubled by all NSAIDs studied, compared with placebo. In addition, COX-2 inhibitors and diclofenac doubled the risk of upper gastrointestinal complications (mainly bleeds), and ibuprofen and naproxen quadrupled the risk compared with placebo.


● Adapted from Eyes on Evidence (September 2013), a bulletin produced by the National Institute for Health and Care Excellence. Available at Reproduced with permission.

● Study sponsorship: UK Medical Research Council and British Heart Foundation.


Louisa Crossley is medicines evidence senior adviser at the Medicines and Prescribing Centre, National Institute for Health and Care Excellence



Readers' comments (2)

  • This summary does need to clarify to the reader the length of time the drugs are taken over before a serious outcome is observed.

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  • It is important to remember that NSAIDs and COXIBS are excellent pain killers and sometimes the risk of serious cardiac side effects can be greater in patients whos pain is poorly controlled. A risk , benefit assessment should be done for each patient.
    This is not a new report and it is important that prescribers do not just stop giving these drugs as often they are the best analgesics and achieving any kind of reasonable pain relief without them will be a struggle and will leave patients in unnecessary pain.

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