Cardiovascular Risks Comparable with Two Pain Killers, Etoricoxib and Diclofenac
Speaker: Christopher P. Cannon, MD, Associate Professor of Medicine, Harvard Medical School, and Associate Physician, Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts
Results from a late-breaking clinical trial showed that etoricoxib (Merck), a highly selective cyclooxygenase-2 (COX-2) inhibitor, and the pain medication diclofenac (Voltaren canadian, Novartis), a COX-1/COX-2 inhibitor, both of which are nonsteroidal anti-inflammatory drugs (NSAIDs), carried comparable rates of thrombotic cardiovascular events.
Selective COX-2 inhibitors, such as rofecoxib (Vioxx, Merck) have previously been implicated in increasing the risk of heart attack and stroke. More recently, evidence suggests that most NSAIDs, whether selective COX-2 inhibitors or not, may also increase cardiovascular risk.
To assess the difference in cardiac risk between these two types of pain agents, investigators conducted the Multinational. Etoricoxib and Diclofenac Arthritis Long-term study program (MEDAL). This is the largest randomized trial ever performed for arthritis. The trial enrolled 34,701 osteoarthritis and rheumatoid arthritis patients from 38 countries, including the U.S. Because all of the patients in the study had debilitating arthritis, there was no placebo group.
The patients, who were older than 50 years of age, had reasons to be using NSAIDs. They were randomly assigned to receive either or 90 mg twice daily or diclofenac 150 mg once daily. The patients were followed for up to three years for an average of 18 months.
The primary endpoint was the rate of any thrombotic cardiovascular event. Overall, there was no hint of any difference in the risk of cardiac events, heart attack, or stroke. There were 1.24 events per 100 years for patients receiving etoricoxib and 1.30 events per 100 years for those taking.
Patients in both groups experienced equal pain relief. The rates of complicated upper gastrointestinal (GI) events leading to perforation or obstruction were also virtually the same with both drugs, one event per 300 patient-years. The rate of uncomplicated ulcers, however, was lower with etoricoxib, for an overall rate of upper GI events of about two events per 300 patient-years, compared with three events per 300 patient-years for drug diclofenac.
Patients receiving high-dose canadian etoricoxib discontinued the study agent more frequently than those receiving the lower dose because of edema. Both doses of etoricoxib were associated with higher rates of discontinuation of therapy as a result of hypertension.