COX-2 inhibitors and the risk of cardiovascular events
COX-2 Inhibitors – The Basics
The cyclo-oxygenase 2 (COX-2) inhibitors are a form of drug in the class of medicines known as the non-steroidal anti-inflammatory drugs (NSAIDs). The COX-2 Inhibitors are a new form of NSAIDs that are considered to produce fewer gastro-intestinal side effects than the older non-selective drugs.
COX-2 inhibitor drugs include:
Celebrex (Celecoxib) Vioxx (Rofecoxib) Bextra (Valdecoxib)
The other COX-2 inhibitors being developed include:
Prexige (Lumiracoxib) Arcoxia (Etoricoxib)
Uses of COX-2 inhibitors
The COX-2 inhibitors have the following usage information highlighted:
Celebrex (Celecoxib) – Commonly prescribed for arthritis and other types of back pain. Vioxx (Rofecoxib) – Prescribed for pain relief from arthritis and back pain in various forms. Bextra (Valdecoxib) – Approved use for signs and symptoms of osteoarthritis and rheumatoid arthritis in adults and painful menstrual cramps.
COX-2 Inhibitors and Cardiovascular Events
Recent research has thrown substantive light on the potential risk of a series of cardiovascular events associated with the use of COX-2 Inhibitors. Patients on a prescription of COX-2 inhibitors have been found to be under a major risk of occurrence of heart attacks, strokes and other cardiovascular events.
Experts indicate that the impact of the COX-2 Inhibitors is attributed to their ability to inhibit endothelial COX-2 derived prostacyclin (PG12). In addition, the COX-2 Inhibitors also interfere with the formation of the lipoxins (Lxs) and resolvins that have neuroprotective and cardioprotective actions.
Research and Trends
Recent research and media reports throw substantive light on the role of the COX-2 Inhibitors in the development a series of cardiovascular events.
To begin with, the pain reliever Vioxx was initially pulled out of the market in 2004 as it was found to increase the risk of heart attack and stroke. Just a few weeks after Merck, the drug maker for Vioxx, stopped selling the drug, Pfizer announced study results linking its painkiller Celebrex to an increased risk of heart attacks.
This was followed by a yet another development when the Vanerbolt University School of Medicine raised questions about the safety of Bextra in a letter to The New England Journal of Medicine. The drug Bextra had recently been found to raise the risk of heart problems in people who had undergone bypass surgery. Finally, the drug was pulled out of the market in April 2005.
The COX-2 Inhibitors like Celebrex and Vioxx, though extremely popular, were found to carry a risk of heart attack in 0.3% to 0.5% of patients .i.e. about 1 in every 300 patients.
In another study, about 8000 people with rheumatoid arthritis were randomly started on a prescription of Vioxx or Naproxen, an NSAID. It was reported that in the patients taking Vioxx, the incidence of cardiovascular events was two times higher. Overall, the annual rates of heart attack in patients taking COX-2 Inhibitors were also increased.
The FDA Regulations
In a recent declaration, the Food and Drug Administration (FDA) released important statements and directions pertaining to the use of COX-2 Inhibitors.
In February 2005, an FDA release directed the Pfizer, Inc. to withdraw Bextra (valdexocib) from the market as the overall potential risks outweighed the benefits of the drug.
In addition, the statement also directed Pfizer, Inc. to include a boxed warning in the Celebrex (celecoxib) label. Consequently, the Pfizer, Inc. agreed to suspend sales and marketing of Bextra in the US and work with the FDA on the boxed warning required on the packaging of Celebrex.
Finally, the FDA also issued supplemental request letters to sponsors of all COX-2 Inhibitors to revise the labelling for their products. The revised labelling or packaging insert is required to include a boxed warning highlighting the potential for increased risk of cardiovascular events and life-threatening gastrointestinal bleeding associated with their use.
After the withdrawal of Vioxx and Bextra from the market, Pfizer has now placed the following warning on Celebrex’s label:
Important Information: CELEBREX may increase the chance of a heart attack or stroke that can lead to death. It should not be used right before or after certain heart surgeries. Serious skin reactions or stomach problems such as bleeding can occur without warning and may cause death.