Gastrointestinal toxicity and cardiovascular toxicity are the two most important safety concerns for non-steroidal anti-inflammatory drugs ( NSAIDs ) and COX-2 inhibitors ( coxibs ).
Clinical trial and epidemiological data have given important information on the level of risk with individual medicines. However, these data are complex and there are no robust comparisons for many NSAIDs.
Most evidence relates to the coxibs, Naproxen, Ibuprofen, and Diclofenac.

Thrombotic risks

In October 2006, the Commission on Human Medicines ( CHM ) gave advice on the latest evidence for cardiovascular thrombotic risks:

• Diclofenac 50 mg daily has a thrombotic risk profile similar to that of at least one coxib ( Etoricoxib ) and possibly others;

• Naproxen 000 mg daily has a lower thrombotic risk than coxibs and, overall, epidemiological data do not suggest an increased risk of myocardial infarction;

• For Ibuprofen at high doses ( eg, 2400 mg daily ) there may be a small thrombotic risk, but at lower doses ( eg, 200 mg daily or less ) epidemiological data do not suggest an increased risk of myocardial infarction

Less evidence is available for other NSAIDs, but they may be associated with a small risk of thrombotic events, especially with long duration of treatment and high doses.

Gastrointestinal risks

The Committee on Safety of Medicines ( now the Commission on Human Medicines ) has reviewed the relative gastrointestinal risks of NSAIDs on several occasions. Recently, the Commission has highlighted the high gastrointestinal risks with Piroxicam, Ketoprofen, and Ketorolac.

Of the traditional NSAIDs, low-dose Ibuprofen offers the lowest risk. Coxibs are associated with reduced gastrointestinal risk relative to most NSAIDs at equivalent doses. However, coxibs ( like NSAIDs ) may vary in their effects, and evidence for a reduction in the most clinically important gastrointestinal risks for Etoricoxib is weak.

Proton pump inhibitors reduce the gastrointestinal risks associated with NSAIDs, and may reduce the risks to a similar level as use of a coxib alone.

Source: MHRA – Drug Safety Update, 2007

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