I have followed the saga of nonsteroidal anti-inflammatory agents (NSAIDs) since Vioxx was withdrawn from the market in 2004. Rather intense reviews of NSAIDs followed with uncertainty about which drugs were the safest to use. As of Sept.2009, the winner is Naproxen, in doses less than 1000 mg per day.
A large retrospective study examined the medical records of 48,566 adults between the ages of 40 and 89 years who were admitted to hospital with coronary artery disease. The databases used came from Canada, the United States, and the United Kingdom. The study found that naproxen was not associated with a higher risk for coronary heart disease events or cardiac death in patients with a history of coronary heart disease. However, ibuprofen; high-dose celecoxib; high-dose rofecoxib; and, diclofenac, did increase this risk.
Relative to naproxen, current users of diclofenac had increased risk of serious coronary heart disease x 1.44 and serious cardiovascular disease/death x 1.52; ibuprofen had increased risk x 1.25; coronary heart disease risk increased for rofecoxib >25 mg x 2.29; celecoxib >200 mg x 1.61.
Recall that in September 2004, Merck & Co announced a voluntary withdrawal of Vioxx from the U.S. and worldwide market due to safety concerns of an increased risk of heart attacks and strokes, according to an alert from MedWatch, the U.S. Food and Drug Administration (FDA) safety information and adverse event reporting program. Vioxx was one of several selective COX-2 inhibitors that were marketed aggressively as the best drugs for pain relief. Because they were prescription drugs and more expensive, patients believed they were better than ASA, ibuprofen, diclofenac or naproxen but this was not true.
The claimed advantage of the COX-2 inhibitors, slightly lower incidence of gastrointestinal bleeding was supported by some but not all studies Cox-2 inhibitors that offered no advantage in terms of pain relief and anti-inflammatory effects. The fate of COX-2 inhibitors has been dismal. A growing controversy surrounded the use of Cox-2 inhibitors since their introduction in 1999. The drug companies involved were competing to secure a large share of the multi-billion-dollar-a-year market for pain-relieving anti-inflammatory drugs. A news report in 2002, for example, warned people that: "Elderly patients taking Vioxx, the most popular arthritis drug in Canada, were twice as likely to be hospitalized with major gastrointestinal bleeding than those taking its pharmaceutical competitor, Celebrex. In 2002, 3.4 million prescriptions for Vioxx were filled across Canada; 3.1 million for Celebrex.
The Therapeutics Initiative Newsletter in BC issued the following COX-2 inhibitors update in 2002: “Based on FDA data from the CLASS and VIGOR studies, COX-2 selective inhibitors are associated with an increased incidence of serious adverse events as compared to non-selective NSAIDs."
Reference: Ray WA, Varas-Lorenzo C, Chung CP, et al. Cardiovascular risks of nonsteroidal antiinflammatory drugs in patients after hospitalization for serious coronary heart disease. Circ Cardiovasc Qual Outcomes 2009; 2:155-163.
From the 2009 book, Heart and Arteries by Stephen Gislason MD