Vioxx, a painkiller once commonly used for joint pain and arthritis, quickly became one of Merck’s best-selling drugs after its debut in 1999. The drug was touted as an effective analgesic for arthritis, with fewer gastrointestinal side effects than traditional nonsteroidal anti-inflammatory drugs (NSAIDS).
But in 2004, the company removed the drug from the market amid concerns about cardiovascular risks, specifically heart attacks and strokes.
The drug’s label had warned of other serious side effects, such as gastrointestinal bleeds, allergic reaction, and kidney and liver problems. It listed the most common side effects of Vioxx as respiratory infections, diarrhea, nausea and headache.
Cardiovascular Risks: Heart Attack and Stroke
Merck’s decision to pull Vioxx (rofecoxib) from pharmacy shelves was based on data from a clinical trial called APPROVe (Adenomatous Polyp Prevention on Vioxx). This study compared the drug to a placebo to determine if a 25-mg dose of Vioxx could prevent the recurrence of colon polyps.
But the trial was halted when it was discovered that the drug led to an increased risk for heart attacks and strokes. Results suggested the drug may have doubled the risk of a stroke or heart attack in patients.
During the trial, 2.4 percent of the 1,287 participants who took rofecoxib suffered a serious cardiac event, including heart attack, angina or sudden death, compared with less than 1 percent of the patients who received a placebo.
A total of 15 patients given rofecoxib had a cerebrovascular event, such as stroke, deadly stroke or transient ischemic attack, while 7 of the participants given a placebo suffered the same reactions.
Some patients who took the drug also developed high blood pressure, fluid build-up known as edema and congestive heart failure, according to a 2005 report in the New England Journal of Medicine.
This increased risk of heart attack was initially determined to be linked to prolonged or chronic use of Vioxx, usually longer than 18 months. However, evidence published in a Canadian journal in 2006 found that approximately 25 percent of patients who suffered a heart attack experienced the cardiac event within two weeks of starting the drug.
Approximately 60,000 Vioxx lawsuits were filed by individuals and family members of people who suffered heart attacks and strokes while taking the drug. Merck settled those cases for close to $5 billion.
“Vioxx was thought by one FDA account to have caused more than 60,000 deaths from myocardial infarction — from heart attacks — and I couldn’t figure out how is it that we as clinicians could be giving patients drugs that were unsafe and not be aware of the carnage we were causing,” Jeanne Lenzer, associate editor at The BMJ told Drugwatch Podcast. “It took a good while for me to learn the answer to that question, but it turns out that it’s quite possible. Doctors only see … maybe they have several thousand patients in their panel that they care for, and if an older man, say taking Vioxx, dies of a heart attack, we just assume, well he was old, and he’s going die of a heart attack.”
How COX-2 Inhibitors Raise Cardiovascular Risks
Since Vioxx’s withdrawal from the market, numerous studies have attempted to explain why the drug increased cardiovascular risks.
Researchers at the Perelman School of Medicine at the University of Pennsylvania concluded in 2012 that the drug’s dangers likely stem from the way it suppresses a chemical called prostacyclin.
Prostacyclin is a prostaglandin, a hormone-like compound made from fats that helps to regulate blood pressure by relaxing the walls of blood vessels. The compound also reduces and removes blood clots.
But Vioxx and other COX-2 inhibitors shut down that mechanism, and in doing so create a “cardiovascular hazard” — or risk factor — comparable to smoking or being a diabetic, according to Dr. Garrett FitzGerald, chair of the department of pharmacology and director of the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania.
COX-2 inhibitors may also promote cardiovascular problems by increasing blood pressure, destabilizing plaque build-up in arteries and causing a hardening of a person’s arteries.
Diarrhea and Nausea Among Most Common Side Effects
Upper respiratory infection was the most commonly reported side effect with Vioxx use, according to the drug’s label. Diarrhea, nausea and other digestive problems were also reported more often, although these occurred less frequently when compared to traditional NSAIDs, such as ibuprofen.
|Vioxx (12.5 or 25 mg daily)||Ibuprofen (2400 mg daily)|
|Diarrhea||6.5 (percent of users)||7.1 (percent of users)|
Other minor side effects of Vioxx included headache, back pain, fatigue, flu-like illnesses, sinus infections, urinary tract infections, bronchitis and dizziness.
Nearly 4 percent of 2,829 patients developed fluid buildup in their legs while using the drug and 3.5 percent developed elevated blood pressure, or hypertension.
GI Bleeds, Kidney Impairment and Liver Problems
Although rare, Vioxx has caused serious gastrointestinal (GI) problems, including stomach and intestinal bleeding and perforation. People who took the drug along with aspirin were at a higher risk of such complications.
Individuals with a history of ulcers or prior episodes of GI bleeding have a 10-fold increased risk for developing a GI bleed than others do when taking NSAIDs. Other factors that may increase this risk include treatment with anticoagulants and treatment with corticosteroids, such as prednisone. Smoking, drinking, older age and poor health can also increase a person’s risk of a GI bleed.
GI bleeds associated with NSAIDs can be hard to recognize because only 20 percent of people develop symptoms.
- Kidney impairment and/or kidney failure
- Severe liver problems, including jaundice, hepatitis and liver failure
- Serious allergic reactions, including anaphylaxis
Please seek the advice of a medical professional before making health care decisions.