Choosing an NSAID with cardiovascular disease: naproxen

NSAIDs (non-steroidal anti-inflammatory drugs) can raise the risk of heart attack, stroke, hypertension and heart failure to varying degrees. The risk is dose and duration dependent, rising as the dose and the length of treatment increase.

Among the non-selective NSAIDs (the older drugs that block both COX-1 and COX-2, the enzymes that make prostaglandins, the chemicals involved in pain, inflammation and clotting), naproxen has the most favourable thrombotic (clot-related) profile. Low-dose ibuprofen, at 1,200 mg a day or less, shares it. Naproxen is also longer-acting, with a half-life of about 14 hours (the time taken for the blood level to fall by half).

At the other end sit diclofenac and the coxibs (the COX-2 selective drugs, celecoxib and etoricoxib). Diclofenac is contraindicated (should not be used) in established cardiovascular disease, including ischaemic heart disease (reduced blood supply to the heart muscle). Coxibs lower prostacyclin, a chemical that widens vessels and discourages platelet clumping, without lowering platelet thromboxane A2, which promotes clotting. That tips the balance towards thrombosis.

Ibuprofen shares naproxen's favourable profile only at low doses. At 2,400 mg a day or more, the risk of heart attack and stroke is higher than with placebo, similar to the coxibs and diclofenac.

Even naproxen is not risk-free. It still raises the chance of stomach and bowel bleeding, so give the lowest effective dose for the shortest time. Naproxen's favourable profile does not guarantee safety in someone with cardiovascular disease.