On September 30, 2004, pharmaceutical manufacturer, Merck & Co., Inc., pulled its popular arthritis and pain medication Vioxx off the worldwide market. Vioxx accounted for $2.5 Billion in sales for Merck last year. This withdrawal came about after a recent study was discontinued due to the increased risk of cardiovascular events, including heart attack and stroke, noticed in patients taking Vioxx as compared to those taking a placebo. As this news has reached the public at large, Plaintiff’s attorneys have been contacted in large numbers regarding what constitutes a claim worth pursuing.
Vioxx is member of the category of medications known as coxibs. Specifically, it is a COX-2 inhibitor. These medications were developed on the hypothesis that by inhibiting on the COX-2 enzyme, rather than both the COX-1 and COX-2 enzymes like traditional non-steroidal anti-inflammatory medications (NSAIDs), the patient could get the anti-inflammatory benefits without the gastrointestinal irritation that is the major complication of NSAIDs.
In January 1999 the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial was initiated to test this theory. In this study the incidence rate of serious gastrointestinal incidents was compared between Vioxx and naproxen, a NSAID also known as naprosyn and sold over the counter as Alleve. The findings of the VIGOR study were presented to the FDA in June 2000, and submitted to the New England Journal of Medicine in November 2000. These results revealed that the incidence rate of serious gastrointestinal events among those receiving Vioxx as compared to those receiving naproxen was half. However, the findings of the study with regard to cardiovascular events were not as favorable. It was noted that in those taking Vioxx, the incidence rate of myocardial infarction was increased five-fold over those taking naproxen. While these results did cause some concern within the medical community, it was suspected that naproxen might have a cardioprotective effect, like other NSAIDs. To date, studies on the cardioprotective nature of naproxen have been inconclusive.
Additionally, Merck documents have come to light to reveal that in as early as May 2000, when the preliminary results of the VIGOR study were coming in for analysis, some of Merck’s top research personnel and marketing executives met to evaluate the need for a study on Vioxx’s cardiovascular impact. This study was deemed impossible because of the sample size that would be needed and the fact that it might send the wrong message in the market at a time when Vioxx was facing stiff competition from Celebrex, a coxib manufactured by Pfizer. Ultimately the decision was made to not go forward with a study examining the cardiovascular effect of Vioxx.
In February 2000, enrollment began in the Adenomatous Polyp Prevention on Vioxx (APPROVe) study. This study was to evaluate the effectiveness of Vioxx in preventing recurrence of colorectal polyps, a known benefit of NSAIDs. The FDA had already approved Celebrex for this usage, and Merck wanted Vioxx to be competitive in this market. The study was comprised of 2600 people with previously removed colorectal polyps and no history of cardiovascular disease. These individuals were taking a 25mg dosage of Vioxx on a daily basis. The external safety monitoring board notified Merck in September 2004 that the midpoint results indicated that the incidence rate of those suffering heart attack and stroke during the trial was nearly double that for those receiving a placebo. Accordingly, after 18 months of testing, the external safety monitoring board recommended that the APPROVe study be terminated prior to its scheduled end date.
It was the recommendation for early termination of the APPROVe study that motivated Merck to withdraw Vioxx from the worldwide market. Merck is offering refunds for Vioxx in the hands of patients and pharmacies. Since the announcement of the withdrawal, other studies have been conducted commingling the results of other evaluations of Vioxx in a backward-looking manner. These studies have also shown an increased incidence rate for cardiovascular events, but as they used existing data and analyzed it as to an issue it wasn’t designed to evaluate, they have been strongly criticized by Merck for failing to group like with like, a basic tenet of statistical review.
DOSAGE NEEDED FOR INCREASE RISK
The VIGOR study had patients taking a 50mg dosage once a day for treatment of arthritis. This dosage is twice the recommended chronic dosage. The APPROVe study showed an increase in the incidence rate for cardiovascular events after 18 months for patients taking 25mg daily. It is unknown at this time if the incidence rate will increase with lesser dosages and for dosages taken for a shorter time period. It should be remembered that those participants in the APPROVe study had been screened and did not have preexisting cardiovascular conditions. Dr. Eric Topol of the Cleveland Clinic has surmised that as the study participants were limited to those without preexisting cardiovascular conditions, the impact on the incidence rate of significant events for those with prior conditions may be much higher. Dr. Garrett FitzGerald, a cardiologist and pharmacologist from the University of Pennsylvania, has opined that after the results of the APPROVe study became known, there is now clear evidence of an increase in cardiovascular risk for those taking Vioxx. Thus, for those with preexisting cardiovascular conditions, a lesser dosage, or one taken for a shorter period of time, may prove sufficient to cause cardiovascular complications. Additionally, how long the patient will be at an increased risk after stopping the medication remains unknown. Vioxx has a short-half life, but it is unknown whether the after-effects remain in the patient’s system for a significant period of time.
The mechanism by which Vioxx causes the increased risk is currently unknown. Dr. FitzGerald has theorized based upon studies with mice that by inhibiting COX-2, the heart protection afforded by estrogen is reduced. It is uncertain though as to if this is the case why the incidence rate of stroke would also be increased. Certainly, clots formed in the heart can be transmitted to the brain and present as stroke, but this seems to be an overly narrow explanation. Other theories are that as COX-2 is the main source of prostaglandin I2, which inhibits platelet aggregation and causes vasodilation, then when Vioxx limits prostaglandin I2 production, it actually causes clot formation and vascular constriction.
CLIENT SYMPTOMS AND COMPLAINTS
As the mechanism by which Vioxx causes an increased risk of cardiovascular events remains unknown, the screening attorney should keep an open mind with regard to possible presentations. Heart attack and stroke are those that the studies have identified at higher rates in patients taking the medication. If Vioxx does cause increased clot formation and vasoconstriction though, other possible complications could include kidney failure, deep vein thrombosis, pulmonary embolus, or transient ischemic attack (TIA).
ISSUES TO CONSIDER WHEN EVALUATING THE CLIENT
The proximate cause of medical events is often unknown. It is an axiom of the defense that medicine isn’t practiced out of a cookbook. That is, patients are individuals with their own body mechanics different from those of all others and what works for some, may not work for others. Thus, when proceeding in a case such as these where causation will be the central issue, the defense will look to point to the patient’s health as established by medical history as being the proximate cause of the injury, rather than Vioxx. It is necessary to identify all predisposing conditions to the complication the client endured, so that you may make a detailed and accurate evaluation of the merits of the claim. Pertinent portions of the patients medical history to consider may include: smoking history, and if they stopped, when did they stop; patient age; high blood pressure, and whether it was controlled by medication; high cholesterol, and if controlled by medication; previous heart attack or stroke; family history of heart disease; diabetes, including type and if controlled; obesity; and stress level.
Establishing the client’s baseline health may also be critical to proceeding with a suit. To do so, the attorney should evaluate and consider what tests are available and the subjective recordings of the client’s physicians. Objective tests may help to establish general baseline health and limit the ability of the drug manufacturer to point to alternative causes. For example, the drug manufacturer would be hard pressed to argue that a client had poor preexisting heart function if cardiac catheterization from before the client began taking Vioxx showed an ejection fraction of 55%. Similarly, the client’s treating physicians may be the greatest asset if prior objective testing hadn’t been performed. The jury often views these physicians as unretained experts and they would have an established relationship with the patient and be most familiar with the patient’s overall medical health. Additionally, there is little chance the treating physician, who lives and works in that community, will take the position that his or her testing and evaluation of the patient failed to uncover a life threatening condition rather than it being the fault of the pharmaceutical giant.
The responsibility of testing to ensure the safety of all prescription drugs in the United States falls to the Food and Drug Administration. While it is naive to expect that all potentially harmful side effects of all medications could be discovered during the testing process, the effort must be made. In instances such as this, Merck knew of potentially deadly side effects of its product in 2000, but failed to act because of concern over how it would appear to the market while it was in the midst of competition with Celebrex from Pfizer. An effort should have been made to confirm the results of the VIGOR study rather than waiting more than four years to withdraw a drug prescribed hundreds-of-thousands-of times in the interim. The task of ensuring that large corporations remain responsible to the American public falls to trial lawyers.