The Vioxx Clinical Studies - Evidence That Vioxx Is Associated with an Increased Incidence of Heart Attack, Stroke and Other Cardiovascular Events.

The public is generally aware that Merck & Co. has recently "recalled" or withdrawn Vioxx from the market and that the manufacturer explained its withdrawal as based upon a recent study which demonstrated an increased incidence of heart attacks in association with Viroxx use.

This most recent finding of the increased incidence of heart attacks, strokes and other adverse reactions with Viroxx use was not the first. Previous studies had demonstrated the same as early as March 2000. And the same findings, of heart attack, stroke, incresed incidence of blood clots and other mostly cardiovascular adverse events were published in a peer review journal in August 2001.

Indeed, long before the most recent study, the FDA had warned Merck that its advertising was false and misleading, specifically for its failure to warn the consumer of the findings of increased incidence of heart attack. And although Merck was urged to do good safety studies to determine the extent of danger posed by Vioxx, this most recent "discovery" that its drug caused heart attacks and other adverse reactions was made in an efficacy study, a study designed to test the utility of Viroxx in the treatment of colon polyps. The study had to be aborted, and the investigational subjects removed from Vioxx treatment when it was determined statistically that they were at a substantially increased likelyhood of heart attack.

The equally important studies, not discussed in Merck's anouncement, were the March 2000 VIGOR (Vioxx Gastrointestinal Outcomes Research) study, and the August 2001 Cleveland Clinic Heart Center study.

Each of these studies demonstates an incresed incidence of heart attacks, strokes and other cardiovascular events in association with Vioxx. In the authors' estimation the studies support the proposition that Merck culpably failed earlier to withdraw the drug from the market. .The Cleveland Clinic Heart Center study was published in the peer reviewed Journal of the American Medical Association in 2001, based upon data compiled in four previous clinical trials of Vioxx (and Celebrex, a similar drug) involving 18,064 patients. (Vioxx belongs to a category of COX-2 selective, nonsteroidal anti-inflammatory drug [NSAIDS]. Celebrex [celecoxib] is another COX-2 selective NSAID.)

Prior to the publication of the Cleveland study the data obtained in the March 2000 VIGOR (Vioxx Gastrointestinal Outcomes Research) study also found an increased risk of cardiovascular events in Vioxx users as compared the incidence of cardiovascular events for users of another pain drug. In Merck's VIGOR study, comparing Vioxx with naproxen, a highly statistically significant five-fold increase in heart attacks was demonstrated in the overall Vioxx group, 0.5 percent compared to 0.1 percent in the naproxen group. This amounted to 20 heart attacks in the Vioxx users (out of 4,047 patients) compared with four in the naproxen users (out of 4,029 patients). This increased number of heart attacks was also accompanied by an increase in other thrombotic (blood clotting) adverse effects such as strokes and blood clots in the legs as well as problems with hypertension in the Vioxx group compared with the naproxen group.

In September 2001, the American Heart Association, the National Stroke Association and the Arthritis Foundation asked Merck to test whether Vioxx increased the risk of heart attack and stroke. In September, 2002, FDA sent Merck a warning letter asserting that the advertising for Vioxx was misleading. The warning letter was sent to Merck President and CEO Raymond V. Gilmartin, stating:

"You have engaged in a promotional campaign for Vioxx that minimizes the potentially serious cardiovascular findings that were observed in the Vioxx Gastrointestinal Outcomes Research (VIGOR) study, and thus, misrepresents the safety profile for Vioxx. Specifically, your promotional campaign discounts the fact that in the VIGOR study, patients on Vioxx were observed to have a four to five fold increase in myocardial infarctions (MIs) compared to patients on the comparator nonsteroidal anti-inflammatory drug (NSAID), Naprosyn (naproxen)."

Merke subsequently changed its advertising to list "heart attack" in the middle of a dozen infrequent Viroxx "side effects," however, without mention of the other adverse reactions, including stroke, also found to be associated with Vioxx use in the VIGOR and Cleveland studies.

The Merck withdrawal of Vioxx, according to the company's press release, was based on adverse data from a recent placebo controlled efficacy study to determine whether VIOXX was efficacious in preventing the recurrence of colon polyps.. That study was stopped after the investigators determined that the data demonstrated that the human subjects taking VIOXX had an increased risk for confirmed cardiovascular events, including heart attack and stroke over those who were receiving the placebo.

In the authors' view, the Vioxx clinical studies are important evidence to demonstrate that Vioxx users who suffered heart attacks in particular, as well as stroke and the other adverse reactions, may have viable causes of action against Merck. In addition, the evidence suggests that Merck may have deliberately turned a blind eye to the mounting evidence of Vioxx adverse reaction data, failing to respond to the pleas of the American Heart Association and Arthritis Foundation, and falsely advertised Vioxx, as implied also by the FDA warning letter.