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Strand V. Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin? Lancet 2007;370:2138–51
A recent review article in the Lancet considers whether patients at risk of cardiovascular (CV) events who are taking prophylactic low-dose aspirin and who also need to take a non-steroidal anti-inflammatory drug NSAID would be better to take a non-selective (traditional) NSAID or a selective COX-2 inhibitor (coxib). Despite stating that trials have not directly answered whether low-dose aspirin is cardioprotective with coxibs, it concludes that coxibs are preferable to non-selective NSAIDs in patients with chronic pain and CV risk who require low-dose aspirin.
This is in contrast to the recent MeReC Extra, produced by the NPC in close collaboration with the MHRA. This also considered the CV and gastrointestinal (GI) safety of NSAIDs. It concluded that coxibs are inappropriate to prescribe to patients who require aspirin for prophylaxis of CV disease because any GI benefits compared to traditional NSAIDs are diminished when they are co-prescribed with aspirin. In addition, coxibs are contraindicated in patients with existing coronary, cerebrovascular or peripheral artery disease. Although there is ex-vivo evidence of an interaction between aspirin and ibuprofen, there is inadequate clinical evidence to suggest that there is a loss in the cardioprotective effect of aspirin when they are given together. The MeReC Extra also points out that co-prescription of a traditional NSAID with a proton pump inhibitor (PPI) appears at least as effective as a coxib alone in reducing GI side effects, and is less expensive.
The Lancet article and the MeReC Extra both acknowledge that comparing CV and GI risks is difficult and that the likelihood and severity of CV events differs between individuals, the NSAID used, and the length of exposure.
Bottom line:
The MeReC Extra notes that coxibs have a higher CV risk than ibuprofen < 1200mg/day or naproxen 1000mg/day. It recommends that low-dose ibuprofen (400mg three times a day) is an appropriate first choice NSAID because CV and GI risks are low at this dose. Naproxen 1000mg/day is an alternative to ibuprofen 1200mg/day and may be preferable to traditional NSAIDs other than ibuprofen 1200mg/day in patients at significant risk of adverse CV effects. Co-prescription of a PPI seems advisable in patients at particular risk of serious GI effects and NICE have this as a draft recommendation for all people taking NSAIDs for osteoarthritis.
The apparently increased rate of CV events with diclofenac and high-dose ibuprofen suggests that, like coxibs, these are less appropriate options for patients in whom CV risk is a significant consideration in decision making.
Prescribing should be based on the safety profiles of individual NSAIDs and on individual patient CV and GI risk factors.
Action:
All NSAIDs carry a risk of serious side effects. To minimise the risk to an individual where an NSAID is required, the lowest effective dose should generally be used for the shortest time necessary to control symptoms, and the need for long-term treatment should be reviewed regularly.
For more information on the CV and GI safety of NSAIDs read the MeReC Extra article or visit the musculoskeletal pain floor of NPC.
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