In the VIGOR study (see above), there was no difference in the total number of deaths, the number of cardiovascular deaths or the incidence of stroke between naproxen and rofecoxib. However, the rofecoxib group had a higher incidence of myocardial infarction (MI) than the naproxen group (0.4 per cent for rofecoxib and 0.1 per cent for naproxen). Professor Bombardier (see also above) suggested that these differences were a result of a positive effect of naproxen (via its COX-1 effects) rather than an increased incidence with rofecoxib.
Patients taking low dose aspirin were excluded from the study. Professor Bombardier said that 4 per cent of the study participants had had a serious cardiovascular event in the past and would normally have been taking aspirin. When this subset of patients was excluded from the results, there was no statistically significant difference in the rate of MI between the rofecoxib (0.2 per cent) and naproxen (0.1 per cent) groups.
Professor Bombardier pointed out that in a meta-analysis of cumulative data from previous studies comparing rofecoxib with other NSAIDs (diclofenac, ibuprofen and nabumetone) and placebo, the rate of MI was the same for rofecoxib and these NSAIDs. It was also the same for rofecoxib and placebo.
The rate for rofecoxib was the same in both VIGOR and the meta-analysis. The key point was that the rate for naproxen was lower, said Professor Bombardier. Her explanation for this was that naproxen was "the most similar traditional anti-inflammatory drug to aspirin in terms of action on platelets". The lower rate of MIs in the naproxen group was consistent with an aspirin-like effect.
A spokeswoman for Merck Sharp & Dohme (manufacturer of Vioxx) told The Journal on May 30 that while previous studies had demonstrated that naproxen blocked platelet aggregation, VIGOR was "by far the largest and longest controlled clinical study involving naproxen in chronic use, which may explain why the suggested cardioprotective effect has not been seen in previous studies of naproxen".
Dr Reicin said that not all NSAIDs inhibited platelet aggregation. Naproxen and flurbiprofen did, but diclofenac and ibuprofen did not. In addition, while aspirin only needed to be taken at a low dose every other day for a cardiovascular effect, NSAIDs had to be taken regularly at the full dosage, she said.
If a patient was prescribed rofecoxib, the physician would have to decide if risk factors that determined the need for aspirin were also present, Dr Reicin added. The MSD spokeswoman commented that, since rofecoxib had no effect on platelet function (measured by bleeding time and platelet aggregation), the drug was not expected to interfere with the cardiovascular benefits of low dose aspirin.