In September of 2004, Merck Pharmaceuticals voluntarily withdrew its popular arthritis drug, Vioxx® (rofecoxib) from pharmacy shelves. This withdrawal, the largest in history, took place after the results of a study revealed that Vioxx was associated with an increased risk of myocardial infarctions, or heart attacks , and strokes . The study that prompted the withdrawal evaluated the efficacy of Vioxx® in patients with gastric polyps. Since the withdrawal, some researchers have come forward maintaining that many patients were put at unnecessary risk because adverse events seen in earlier studies of Vioxx® were never investigated.

Rofecoxib, or Vioxx® is known as a COX-2 inhibitor. These agents are a subset of non-steroidal anti-inflammatory agents, or NSAIDs. Their development was considered a benefit for patients, as COX-2 drugs appeared to provide the pain relief of NSAIDs, but without the stomach irritation that many patients experienced with NSAIDs. Other COX-2 inhibitors include celecoxib (Celebrex®) and valdecoxib (Bextra®). These COX-2 drugs remain on the market.

While COX-2 inhibitors are associated with a lower incidence of gastric side effects, they are not harmless. In fact, the idea that Vioxx® is associated with cardiovascular risks is not a new one. Some researchers maintain that this risk was evident as early as 1999, the year Vioxx® was approved for use in the US. A study published in the November 5, 2004 issue of The Lancet evaluated 29 studies involving Vioxx® to see whether evidence of its adverse cardiovascular effects was available before September 2004.

About the Study

This study was a meta-analysis of 29 studies obtained from Food and Drug Administration (FDA) databases of previously conducted studies. Researchers draw conclusions from a meta-analysis by pulling together the results of a number of other studies. Studies that compared Vioxx® with either other NSAIDs or a placebo were considered for the meta-analysis. The patient population of the studies included patients with musculoskeletal disorders, such as osteoarthritis , rheumatoid arthritis , or lower back pain . For each of these studies, the researchers evaluated the incidence of myocardial infarction.

The Findings

The authors found 64 cases of myocardial infarction in the studies performed in 2000. Of these cases, 52 occurred in patients taking Vioxx®, while 12 occurred in patients in the placebo group. The dosage of Vioxx® did not seem to have an effect on the risk of myocardial infarction. Statistically, the results of the study showed that patients taking Vioxx® were at an increased risk of myocardial infarction.

The authors concluded that there was enough evidence to withdraw Vioxx® from the market in 2000 and argue for an immediate investigation into the reasons why the drug was allowed to remain on the market.

One of the limitations of this meta-analysis is that it only evaluated studies with patients who were diagnosed with musculoskeletal disorders (arthritis or low back pain). It is possible, but unlikely, that patients taking Vioxx for other reasons would have been spared the increased cardiovascular risk.

How Does This Affect You?

At the time of its withdrawal, Vioxx® was used by an estimated 80 million people, and in the US, sales had reached 2.3 billion dollars. An increased cardiovascular risk to even a small percentage of these patients translates to a huge number of patients put at risk. The number of people impacted by the adverse effects of this drug is yet unknown. Some estimates maintain that Vioxx® may be responsible for 27,000 excess cases of acute myocardial infarction and sudden cardiac deaths between 1999 and 2003.

When faced with this evidence, it is unclear why Merck would not have come forward years earlier to withdraw an apparently dangerous drug from the market, or at least aggressively investigate its risks. What is also uncertain is why the FDA took no action either. The public must rely on pharmaceutical companies and especially the FDA to protect them from unsafe drugs. Unfortunately, the reputation of both of these groups has been stained by this incident, and regaining the public trust may take time.

As the researchers stated at the end of the study, immediate investigation is warranted. Indeed, there are two other COX-2 agents that are still available (Celebrex® and Bextra®), as well as other COX-2 drugs in development. Despite initial claims that Celebrex® is free of cardiovascular risk, it is imperative that researchers evaluate whether this is a class effect. (That is, whether all the agents in this class are associated with increased cardiovascular risk), or if it’s isolated to Vioxx®.

If you are taking a COX-2 inhibitor, speak to your doctor right away. While these drugs have their advantages, there are many other effective strategies for treating chronic pain.