Treatment with certain COX 2 inhibitors, non-steroidal anti-inflammatory drugs that relieve the pain associated with arthritis, may increase the risk of heart attack, according to a retrospective analysis of two separate marketing studies.
The research comes within weeks of the National Institute for Clinical Excellence approving these types of drug for use in the NHS in England and Wales. The institute acknowledged in a recent technology appraisal guidance bulletin (No 27, July 2001; www.nice.org.uk) that there is such a risk and that COX 2 inhibitors should not be prescribed routinely to patients with cardiovascular disease.
Researchers from the Cleveland Clinic Foundation in Ohio analysed the cardiovascular event rates in two randomised multicentre trials. They also looked at myocardial infarction rates in the placebo group (23407 patients) in a meta-analysis of four large aspirin studies.
They found that the annual myocardial infarction rate in the aspirin placebo group was 0.52% This compared with 0.74% (P=0.04) for the COX 2 inhibitor rofecoxib (Vioxx) in the Vioxx gastrointestinal outcomes research (VIGOR) study and 0.80% for the inhibitor celecoxib (Celebrex) in the celecoxib long term arthritis safety study (CLASS) (JAMA 2001;286: 954-9).
Aspirin use was not permitted in the VIGOR study, in which 8076 patients were randomised to receive rofecoxib 50 mg a day or naproxen 1000 mg a day. There were 111 cardiovascular events in the rofecoxib arm and 50 events in the naproxen arm.
However, aspirin use was permitted in the CLASS study, in which 8059 patients were randomised to 400 mg of celecoxib twice a day, 800 mg of ibuprofen three times a day, or 75 mg of diclofenac twice a day.